Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

I. Reactions of omega-linked disaccharides. II. Synthesis of the 2,4-di-O-methyl Slessor, Keith Norman 1964

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1964_A1 S6.pdf [ 5.3MB ]
Metadata
JSON: 831-1.0062249.json
JSON-LD: 831-1.0062249-ld.json
RDF/XML (Pretty): 831-1.0062249-rdf.xml
RDF/JSON: 831-1.0062249-rdf.json
Turtle: 831-1.0062249-turtle.txt
N-Triples: 831-1.0062249-rdf-ntriples.txt
Original Record: 831-1.0062249-source.json
Full Text
831-1.0062249-fulltext.txt
Citation
831-1.0062249.ris

Full Text

I. II.  REACTIONS OF o£-LINKED DISACCHARIDES SYNTHESIS OF THE 2,4-DI-O-METHYL TETROSES by KEITH NORMAN SLESSOR  B.Sc., The U n i v e r s i t y of B r i t i s h Columbia, 1960 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n the Department of CHEMISTRY  We accept t h i s t h e s i s as conforming to the required  standard  THE UNIVERSITY OF BRITISH COLUMBIA August, 1964  In presenting this thesis i n p a r t i a l fulfilment of the requirements for an advanced degree at the University of B r i t i s h Columbia, I-agree that the Library shall make i t available for reference and study*  freely  I further agree that per-  mission for extensive copying of this thesis for scholarly purposes may be granted by the Head of my Department or by his representatives.  It i s understood that copying or publi-  cation of this thesis for financial gain shall not be allowed without my written permissions.  V Department of The University of B r i t i s h Columbia, Vancouver 8, Canada  The U n i v e r s i t y  of B r i t i s h  Columbia  FACULTY OF GRADUATE STUDIES  PROGRAMME OF THE FINAL ORAL EXAMINATION FOR. THE  DEGREE OF  DOCTOR OF PHILOSOPHY  of  KEITH NORMAN SLESSOR  B.Sc,  The U n i v e r s i t y  TUESDAY  3  o f B r i t i s h Columbia, 1960  SEPTEMBER 15th, 1964, AT 10i30 A.M.  IN ROOM 261, CHEMISTRY BUILDING  COMMITTEE IN CHARGE Chairman: I . McT. Cowan G.G.S, Dutton L.D. H a l l J.P. Kutney C,A. McDowell External  Examiner: P r o f e s s o r  Queens U n i v e r s i t y ,  T„ Money A. Rosenthal G.M„ Tener J. Trotter J.K.N. Jones F.R.S.  Kingston  I. II.  Reactions  of <X-Linked D i s a c c h a r i d e s  S y n t h e s i s of the 2,4-Di-O-Methyl. T e t r o s e s ABSTRACT  L  R e a c t i o n s ofc<-Linked  Disaccharides  Through r e a c t i o n of s p e c i f i c a l l y s u b s t i t u t e d maltoses, c < - g l u c o s i d i c d i s a c c h a r i d e d e r i v a t i v e s have been prepared. C a t a l y t i c o x i d a t i o n of b e n z y l ^ - m a l t o s i d e yielded maltobiouronic acid. T r i t y l a t i o n of 1,6-anhydro"maltose made p o s s i b l e the p r e p a r a t i o n of the 6'.-0= tosyl ester. Replacement of the t o s y l a t e w i t h a z i d e i o n f o l l o w e d by r e d u c t i o n and h y d r o l y s i s y i e l d e d a small amount of 6 ' --amino^.6 ' deoxy^maltose. Replacement of the t o s y l a t e w i t h t h i o l a c e t a t e allowed the preparat i o n of 6'-deoxy-6 -mercapto-maltose. I o d i d e r e p l a c e ment: of t h e s u l p h o n y l e s t e r f o l l o w e d by r e d u c t i o n gave the 6 -deoxy-1,6-anhydro d e r i v a t i v e which was c o n v e r t e d to 6 -deoxy-maltose by a c e t o l y s i s and d e a c e t y l a t i o n . 1  1  1  A r o u t e f o r the p r e p a r a t i o n of 4^0- (oC-D-glucopyr a n o s y l u r o n i c a c i d ) - D ^ x y l o s e by s e l e c t i v e d e c a r b o x y l a t i o n of m a l t o s y l d i u r o n i c a c i d was .attempted and found u n f e a s i b l e . Attempts t o prepare 6 - s u b s t i t u t e d maltoses by r e a c t i o n of benzyl. 4', 6 '-0~benzylidenejS-maltoside w i t h v a r i o u s reagents were u n s u c c e s s f u l . II.  S y n t h e s i s of the 2,4-Di-O-Methyl T e t r o s e s  The four i s o m e r i c 2,4-di-O-mefchyl t e t r o s e s were prepared by p e r i o d a t e o x i d a t i o n o f known methylated sugars. 2,4-.Di-0-methyl-D"and L ~ e r y t h r o s e s were prepared from 4,6-di-O-methyl-D-glucose and 3j5-di-0-methyl-Larabinose r e s p e c t i v e l y . 2,4-Di-0-methyl-D»and Lt h r e o s e s were prepared from 3,5-di-0~methyl~D-xylose and 1,4,6-tri-O-methyl-L-sorbose. The t e t r o s e s were c h a r a c t e r i z e d as t h e i r c r y s t a l l i n e 2,4-di.nitrophenylhydrazones. The Rf and RQ v a l u e s of the f r e e sugars were r e c o r d e d i n a v a r i e t y o f s o l v e n t s i n c l u d i n g a s i l i c a g e l t h i n - l a y e r chromatography system. -  GRADUATE Field  of Study;  Topics  STUDIES  Organic Chemistry  i n Organic Chemistry  J.P. Kutney D,E McGreer R,E, P i n c o c k =  Carbohydrate  Chemistry  P h y s i c a l Organic Chemistry R e a c t i o n Mechanisms Natural  G,G,S, Dutton L,D. Hayward A. Rosenthal R. Stewart R.E. P i n c o c k  Products  A.I.  Scott  Newer S y n t h e t i c Methods  G . C S , Dutton A. Rosenthal  Polysaccharide  G,GoS.  Related  Chemistry  Dutton  Studies;  Topics  i n P h y s i c a l Chemistry  A, Bree J.R. Coope R Snider 0  Topics  Crystal  i n Inorganic  Structure  Chemistry  H. B a r t l e t t : H.C. C l a r k W.R. C u l l e n N„  Bartlett S„ Melzak J. Trotter  PUBLICATIONS  S.A, Black, G.G.S. Dutton and K.N. S l e s s o r , " S y n t h e t i c D i s a c c h a r i d e s " , Advances i n Carbohydrate Chemistry, accepted f o r p u b l i c a t i o n . G.G.S. Dutton and K.N. S l e s s o r , " S y n t h e s i s of t h e 2,4,Di.-0-Methyl T e t r o s e s " , Canadian J o u r n a l of Chemistry, X L I I (1964), pp. 614-619. G.G.S. Dutton and K.N. S l e s s o r , " S y n t h e s i s o f Maltobiouroni.c A c i d (4-0(6<cDG l u c o p y r a n o s y l - u r o n i c A c i d ) ~ D - g l ucose)", Canadian J o u r n a l of Chemistry, XLII (1,964),  pp.11.10-1112.  -iiABSTRACT Chairman: P r o f e s s o r G. G. S. Dutton I.  REACTIONS OF ©<-LINKED DISACCHARIDES  Through r e a c t i o n of s p e c i f i c a l l y s u b s t i t u t e d maltoses, <X-glucosidic Catalytic  d i s a c c h a r i d e d e r i v a t i v e s have been  o x i d a t i o n of b e n z y l  maltobiouronic  acid.  ^-maltoside  prepared.  yielded  T r i t y l a t i o n of 1,6-anhydro- f§ -maltose  made p o s s i b l e the p r e p a r a t i o n of the 6 * - 0 - t o s y l e s t e r . Replacement of the t o s y l a t e with azide ion f o l l o w e d by r e d u c t i o n and h y d r o l y s i s y i e l d e d a small amount of 6'-amino-6 -deoxy1  maltose. allowed  Replacement of the t o s y l a t e with t h i o l a c e t a t e the p r e p a r a t i o n of 6 -deoxy-6 -mercapto-maltose. 1  1  Iodide replacement of the s u l p h o n y l e s t e r f o l l o w e d by r e d u c t i o n gave the 6'-deoxy-l,6-anhydro d e r i v a t i v e which was  converted  to 6 -deoxy-maltose by a c e t o l y s i s and d e a c e t y l a t i o n . 1  A route f o r the p r e p a r a t i o n of 4-0-(0< -D-glucopyranosylu r o n i c a c i d ) - D - x y l o s e by s e l e c t i v e d e c a r b o x y l a t i o n m a l t o s y l d i u r o n i c a c i d was Attempts to prepare  attempted and found  1  were u n s u c c e s s f u l .  infeasible.  6 - s u b s t i t u t e d maltoses by r e a c t i o n of  benzyl 4 ,6 -O-benzylidene- ^-maltoside 1  of  with v a r i o u s  reagents  -iii-  II.  SYNTHESIS OF THE 2,4-DI-O-METHYL TETROSES  The f o u r i s o m e r i c 2,4-di-0-methyl t e t r o s e s were prepared by p e r i o d a t e o x i d a t i o n of known methylated  sugars.  0-methyl-D-and L - e r y t h r o s e s were prepared from methyl-D-glucose  4,6-di-0-  and 5,5-di-0-methyl-L-arabinose  respectively.  2,4-Bi-O-methyl-D- and L-threoses were prepared from O-me t h y l - D - x y l o s e and The  2,4-Di-  3,5-di-  1,4,6-tri-O-methyl-L-sorbose.  t e t r o s e s were c h a r a c t e r i z e d as t h e i r  2,4-dinitrophenylhydrazones.  The Bj. and R  Q  crystalline  values of the  f r e e sugars were recorded i n a v a r i e t y of s o l v e n t s i n c l u d i n g a silica  g e l t h i n - l a y e r chromatography system.  - i v-  TABLE OP CONTENTS I.  REACTIONS OF  -LINKED DISACCHARIDES Page No.  INTRODUCTION  1  Purpose  1  Chemical  S y n t h e s i s of c>_-Glucosidic D i s a c c h a r i d e s  Koenigs-Knorr S y n t h e s i s I n v e r s i o n a t Carbon 2 Condensation v i a 1,2-Anhydro Rings Anomerization M o d i f i c a t i o n Reactions  3 5 5 7 8  P r o t e c t i o n of the Reducing F u n c t i o n Use of Anhydro Rings Use of E s t e r s Use of E t h e r s Use of A c e t a l s and K e t a l s E p i m e r i z a t i o n s and I n v e r s i o n s METHODS OF SYNTHESIS Maltobiouronic Acid  3  9 12 13 17 20 21 23  (4-O-(0C-D-Glucopyranosyluronic  Acid)-D-glucose 4-0-(oC-D-Glucopyranosyluronic  23 Acid)-D-xylose  4-0-(6-Amino-6-deoxy- o£-D-glucopyranosyl)-D-glucose  25 28  4-0-(6-Deoxy-6-mercapto-6C-D-glucopyranosyl)-Dglucose  32  4-0-(6-Deoxy-o£-D=glucopyranosyl)-D-glucose  34  4-0-( 3-Amino-3-deoxy-<X.-D-glycopyranosyl)-D-glucose Attempts to Synthesize 4-0-(o<. - B - G l u c o p y r a n o s y l ) 6-deoxy-6-substituted-D-glucose D e r i v a t i v e s  36 45  - V-  Page No. DISCUSSION  46  Maltobiouronic Acid  46  A c i d H y d r o l y s i s of 1,6-Anhydrides  47  A c e t o l y s i s of 1,6-Anhydrides  48  Mercapto Sugars  51  Comparative R e a c t i v i t y of Primary Hydroxyl Groups  53  EXPERIMENTAL  54  Benzyl Hepta-O-ace tyl-|?>-maltoside  54  Benzyl  |?>-Maltoside  55  Platinum O x i d a t i o n C a t a l y s t  55  Catalytic  Oxidation of Benzyl  |£-Maltoside  Methyl(Benzyl Hepta-O-acetyl- ^ - m a l t o s i d ) u r o n a t e Barium(Benzyl  |3 - M a l t o s i d ) u r o n a t e  56 57  Maltobiouronic Acid Methyl(Hepta-0-acetyl-  56  58 -maltosid)uronate  59  C o n s t i t u t i o n of M a l t o b i o u r o n i c A c i d  59  Reaction of Benzyl Hepta-O-acetyl- &-maltoside with LiAlH  60  r 4  1,6-Anhydro- ^-maltose  61  D i r e c t T o s y l a t i o n of 1,6-Anhydro-^-maltose  61  l , 6 - A n h y d r o - 6 ' - O - t r i t y l - ^ -maltose  62  P e n t a - 0 - a c e t y l - l , 6 - a n h y d r o - 6 ' - O - t r i t y l - ^-maltose  62  2,2' ,3,3' ,4'-Penta-0-acetyl-l,6-anhydro- |5 -maltose  63  Penta-0-acetyl-l,6-anhydro-6 ' - 0 - t o s y l -  63  -maltose  -vi-  Page No. Penta-0-acetyl-l,6-anhydro-6 -azido-6 -deoxy- (I 1  1  maltose  64  6 -Amino-6 -deoxy-maltose  65  Potassium  66  1  1  Thiolacetate  Penta«=0-acetyl-6 -S-acetyl-l,6-anhydro-6 -deoxy1  1  P-maltose  67  Hepta-O-acetyl-6'-S-acetyl-6'-deoxy-  oC-maltose  6'-Deoxy-6'-mercapto-maltose Penta-O-acetyl-l,6-anhydro-6  67 68  • -deoxy-6 ' -iodo-(5 -  maltose Penta-O-acetyl-l,6-anhydro-6'-deoxy-  69 ^-maltose  69  6'-Deoxy-maltose  70  Hepta-O-acetyl-6'-deoxy- ^-maltose  71  C a t a l y z e d Lead T e t r a a c e t a t e Oxidations Methyl ©i-D-Glucopyranoside 1,6-Anhydro-y3-D-glucose  71 71 72  Benzyl 4 ,6 '-0-Benzylidene-6-0-tosyl- |5 -maltoside 1  Benzyl 4 , 6 ' - 0 - B e n z y l i d e n e - 6 - 0 - t r i t y l - ^ -maltoside 1  B e n z y l 4 ,6 '-0-Benzylidene-6-0-mesyl-/3 -maltoside 1  BIBLIOGRAPHY  72 75 73 75  -vii-  Page No. II.  SYNTHESIS OF THE 2,4-DI-O-METHYL  TETROSES  INTRODUCTION  82  Purpose  82  Background  83  METHODS OF SYNTHESIS  87  2,4-Di-O-methyl-D-erythrose  87  2,4-Di-0-methyl-L-erythrose  89  2,4-Di-O-methyl-D-threose  90  2,4-Di-0-methyl-L-threose  92  DISCUSSION  98  Incomplete  P e r i o d a t e O x i d a t i o n of Reducing  Sugars  98  Chromatography  100  Anomalous Behaviour of O p t i c a l Isomers  102  Derivatives  105  EXPERIMENTAL P r e p a r a t i o n of the S i l i c a  106 Gel Column  S y n t h e s i s of 2,4-Di-0-methyl-D-erythrose 4,6-Di-O-methyl-D-glucose 4,6-Di-O-methyl-B-glucitol 4 , 6 - D i - 0 - m e t h y l - D - g l u c i t o l phenylurethan 2,4-Di-O-methyl-D-erythrose 2.4- Dinitrophenylhydrazone of 2,4-di-0methyl-B e r y t h r o s e S y n t h e s i s of 2,4-Di-0-methyl-L-erythrose 3.5- Di-0-methyl-L-arabinose 3,5-Di-O-methyl-L-arabinonolactone  106 107 107 107 108 108 109 109 109 110  -viiiPage No. 3,5-Di-O-me thyl-L-arabinonamide 3,5-Bi-O-methyl-L-arabinitol 2,4-Di-0-methyl-L-erythrose 2.4- Dinitrophenylhydrazone of 2,4-di-0methyl-L-erythrose S y n t h e s i s of 2,4-Di-O-methyl-D-threose 1.2- Isopropylidene-D-xylofuranose 3.5- D i - 0 - m e t h y l - l , 2 - i s o p r o p y l i d e n e - D xylose 3,5-Di-0-methyl-B-xylose p-Bromophenylosazone of 3,5-di-0-methyl-Dxylose 3,5-Di-0-methyl-D-xylitol 2,4-Di-0-methyl-B-threose 2,4-Dinitrophenylhydrazone of 2,4-di-0-methylD-threose S y n t h e s i s of 2,4-Di-0-methyl-L-threose 2.3- I s o p r o p y l i d e n e - l , 4 , 6 - t r i - 0 - m e t h y l - L sorbose l,4,6-Tri-0-methyl-L-sorbose l,4,6-Tri-0-methyl-hexitol 2.4- Di-0-methyl-L-threose 2,4-Dinitrophenylhydrazone of 2,4-di-0-methylL-threose BIBLIOGRAPHY  110 110 111 111 112 112 112 112 113 113 113 114 114 114 115 115 116 116 117  -ix-  LIST OF FIGURES AND I.  TABLES  REACTIONS OF o(-LINKED DISACCHARIDES Page No,  Figure  1.  Synthesis  of Maltobiouronic  Acid  24  Figure  2.  Synthesis of 4-0-(o^-D-Glucopyranosyl uronic Acid)-D-xylose  26 29  Figure  3.  Synthesis  Figure  4.  A l t e r n a t e Synthesis maltose  Figure  5.  Synthesis  of 6'-Deoxy-6'-Mercapto-maltose  33  Figure  6.  Synthesis  of 6'-Deoxy-maltose  35  Figure  7.  Synthesis  of 3-Amino-3-deoxy-sugars  37  Figure  8.  Synthesis of 4-0-(3-Amino-3-deoxy-c^D-glycopyranosyl)-D-glucose  Figure  9.  of 6•-Amino-6'-deoxy-maltose of 6 -Amino-6 -deoxy1  1  31  40  Conformational Models of l,6-Anhydro-/3 maltose  42  F i g u r e 10.  C a t a l y z e d Lead Tetraacetate  Figure 11. Figure 12.  Thin Layer Chromatography of A c e t o l y s i s Proposed A c e t o l y s i s Mechanism  50 52  Table  Catalyzed Lead T e t r a a c e t a t e  72  1.  Oxidation  Oxidation  N  43  -X-  II.  SYNTHESIS OF THE 2,4-DI-O-METHYL  TETROSES Page No.  F i g u r e 1.  Synthesis  of 2,4-Di-O-methyl-D-erythrose  88  Figure 2.  Synthesis  of 2,4-Di-O-methyl-L-erythrose  91  Figure 3.  Synthesis  of 2,4-Di-O-methyl-D-threose  93  F i g u r e 4.  Synthesis  of 2,4-Di-0-methyl-L-threose  95  Figure  Reduction of 1,4,6-Tri-O-methyl-L-sorbose  5.  F i g u r e 6.  5-Aldo-l,2-0-isopropylidene-D-xylopentofuranose  F i g u r e 7.  P o s s i b l e S t r u c t u r e of C r y s t a l l i n e me thyl-D-threose  Table  P h y s i c a l P r o p e r t i e s of 2,4-Di-0-methyl  1.  97 104  2,4-Di-O-  104  Tetroses 101  -xi-  • ACKNOWLEDGEMENTS  I would l i k e people  to g r a t e f u l l y acknowledge the e f f o r t s of two  on ray b e h a l f .  The f i r s t ,  P r o f e s s o r G. G. S. Dutton,  has p r e s i d e d over ray s t u d i e s with a l e n i e n t but steady His l e a d e r s h i p has encouragement.  been a deep source  hand.  of ideas and  I t has been a pleasure to work under the  i n f l u e n c e of such a g e n i a l person.  The second, my w i f e ,  Marie, has p a t i e n t l y endured the d u r a t i o n of ray s t u d i e s . constant encouragement has been a welcome help d u r i n g  Her  this  time.  I would l i k e initial  manuscript  to thank Dr. P h i l Reid f o r r e a d i n g the and o f f e r i n g many h e l p f u l  I would a l s o l i k e of  suggestions.  to thank the N a t i o n a l Research C o u n c i l  Canada f o r the award of s t u d e n t s h i p s f o r the d u r a t i o n of  my s t u d i e s .  I.  REACTIONS OF at-LINKED  DISACCHARIDES  INTRODUCTION * Purpose In s p i t e of the polysaccharides, for  no  importance of s t a r c h and  s a t i s f a c t o r y method has been developed  s y n t h e s i z i n g the oi - g l u c o s i d i c l i n k a g e .  have been t r i e d , but oC-glucosides  s i m i l a r food  Many approaches  i n n e a r l y a l l cases the  has been hindered  by very low  synthesis y i e l d s of  of the  d e s i r e d product. An  obvious route  remains f o r the  c o n t a i n i n g o£ - l i n k a g e s .  synthesis  of  This i s the m o d i f i c a t i o n  disaccharides of n a t u r a l l y  o c c u r r i n g d i s a c c h a r i d e s having the oC - g l u c o s i d i c c o n f i g u r a t i o n . The  r e a c t i o n s commonly used i n monosaccharide c h e m i s t r y  have seldom been e f f e c t i v e l y a p p l i e d to d i s a c c h a r i d e s . to the ease of h y d r o l y s i s of the g l y c o s i d i c bond, no in  a s y n t h e t i c sequence may  As d i s a c c h a r i d e s  contain  employ s t r o n g l y a c i d i c  twice as many hydroxyl  reaction  conditions.  groups,  r e a c t i o n s normally e x h i b i t i n g s e l e c t i v i t y i n simpler often f a i l when a p p l i e d to d i s a c c h a r i d e s .  The  n o r m a l l y a s s o c i a t e d with a s p e c i f i c hydroxyl d r a s t i c a l l y a l t e r e d by proximity  #  of the  two  systems  reactivity  group may  s t e r i c f a c t o r s o r i g i n a t i n g from  sugar u n i t s .  Due  be the  I t i s obvious that  The f o l l o w i n g c o n v e n t i o n a l a b b r e v i a t i o n s have been used throughout the t e x t r t o s y l - Ts (p-toluenesulphonyl), mesyl = Ms (me thane s u l p h o n y l ) , ana! t r i t y l = Tr ( t r i p h e n y l m e t h y l ) . A l l ring-hydrogen atoms are omitted i n the Haworth s t r u c t u r e s .  -2-  i n d i s c r i m i n a t e use of general  procedures employed i n  monosaccharide c h e m i s t r y w i l l not be s u c c e s s f u l . R e a c t i o n s employed i n modifying d i s a c c h a r i d e s on p r e f e r e n t i a l e t h e r i f i c a t i o n  may r e l y  of primary h y d r o x y l groups,  or b l o c k i n g  of s p e c i f i c a l l y o r i e n t e d h y d r o x y l s by a c e t a l s  or k e t a l s .  A r a t h e r unique f u n c t i o n a l group, the 1,6-  anhydro-linkage, enables simultaneous b l o c k i n g primary h y d r o x y l of the reducing reducing  function i t s e l f .  permit the m o d i f i c a t i o n  of the  sugar as w e l l as the  The use of such r e a c t i o n s may  of d i s a c c h a r i d e s  In an e f f o r t to e l u c i d a t e are a p p l i c a b l e t o d i s a c c h a r i d e  at s p e c i f i c  some of the r e a c t i o n s  positions. that  chemistry, attempts t o  prepare s p e c i f i c a l l y s u b s t i t u t e d maltose d e r i v a t i v e s were undertaken.  Maltose, 4-0-(oC-D-glucopyranosyl)-D-glucose,  was chosen f o r three oC-linked  reasons.  disaccharide  a c t i o n of v a r i o u s  Maltose i s the most common  containing  glucose.  Secondly, the  h y d r o l y t i c enzymes upon m o d i f i e d  should provide some i n f o r m a t i o n  on the s p e c i f i c i t y of these  enzymes.  This i n t u r n may provide i n f o r m a t i o n  structure  of s t a r c h .  substituents  maltoses  on the f i n e  F i n a l l y , the i n t r o d u c t i o n of r e a c t i v e  i n t o a m y l i t o l (1, 2) has provided  with r a d i c a l l y d i f f e r e n t p r o p e r t i e s .  derivatives  Synthetically altered  maltoses would provide not only model compounds f o r such s t u d i e s , but a l s o r e f e r e n c e obtained by p a r t i a l  compounds f o r comparison of products  hydrolysis.  Chemical Synthesis  of Q< - G l u c o s i d i c  Koenigs-Knorr  Disaccharides  Synthesis  Although s e v e r a l methods e x i s t f o r the p r e p a r a t i o n disaccharides,  the method g e n e r a l l y used i s the  of hydrogen h a l i d e between a g l y c o s y l h a l i d e and group.  The  r e a c t i o n i s c a r r i e d out  a c i d acceptor which may mechanism.  The  Knorr ( 3 ) , who  by Koenigs  an  and  condensed acetobromglucose with methanol i n a c i d acceptors.  I f the  with a monosaccharide p o s s e s s i n g results.  other l e s s common methods of s y n t h e s i s  the  subject  of three reviews ( 4 , 5,  6).  of s y n t h e t i c d i s a c c h a r i d e s  one  methanol free  This r e a c t i o n  the  The  a hydroxyl  i n the presence of  introduced  h y d r o x y l group, a d i s a c c h a r i d e  tabular l i s t  elimination  take p a r t d i r e c t l y i n a c o n c e r t e d  r e a c t i o n was  the presence of v a r i o u s i s replaced  of  and  have been  Recently a has been prepared ( 7 ) .  replacement of the bromide i n the  Koenigs-Knorr  r e a c t i o n g e n e r a l l y proceeds with an i n v e r s i o n of carbon atom one.  The  opposite The  product of the r e a c t i o n possesses t h e r e f o r e , configuration  configuration  to the r e a c t a n t  glycosyl halide.  of the h a l i d e i n acetobromglucose  been found to be cK. •  The  at the  has  reasons f o r t h i s have been  summarized by Lemieux ( 8 ) , " i n the absence of l a r g e substituents  the  3- or 5 - p o s i t i o n s , the  s t a b l e anoiaer f o r g l y c o p y r a n o s y l  axial  thermodynamically  h a l i d e s i s the anomer which  -4-  has  the halogen i n a x i a l o r i e n t a t i o n " .  Thus, the  Koenigs-  Knorr r e a c t i o n proceeds with acetobromo glucose to mostly the A  |8 - g l u c o s i d e .  - g l u c o s y l h a l i d e might be  expected to give  d e s i r e d d. -anomer upon r e a c t i o n , but that the 1,2-trans h a l i d e - a c e t o x y of an orthoacetate configuration  intermediate,  (9).  The  use  s t u d i e s have shown  preserving  the  perchlorate  repeated (11).  The  a non-participating power of the  three  synthesis  non-  gave isomaltose yield  l a t e r a t t r i b u t e d to a very a c t i v e  c a t a l y s t , the  way  initial  of a n i t r o e s t e r as a  (6-0-(c< -D-glucopyranosyl)-D-glucose) i n high This y i e l d was  the  system r e a c t s by  p a r t i c i p a t i n g group at p o s i t i o n two  function  give  (10).  silver  of which could not  be  t r i c h l o r o a c e t y l e s t e r has been used  as  group, since the e l e c t r o n withdrawing c h l o r i n e atoms of the t r i c h l o r o a c e t y l  should d e a c t i v a t e  the  carbonyl  to such an  extent  t h a t i t would be unable to a s s i s t i n the displacement of halide  (11,  The  12).  e f f e c t of c a t a l y s t s , condensing agents, and  of r e a c t a n t s  has  non-participating obtain  the  been e x t e n s i v e l y  ratio  s t u d i e d i n the case of  the  ^ - g l u c o s y l c h l o r i d e s , i n an attempt to  reproducible  high  yields.  Condensations to  primary 6 p o s i t i o n were r e a s o n a b l y s u c c e s s f u l .  the  However,  condensations at secondary p o s i t i o n s , f o r example k o j i b i o s e (2-0-(©C - D - g l u c o p y r a n o s y l ) - D - g l u c o s e ) , gave very low  yields  (11).  -5-  Future i n v e s t i g a t i o n s of more r e l i a b l e c a t a l y s t s provide higher y i e l d i n g condensations.  may  At p r e s e n t , the  p r e p a r a t i o n of o C - l i n k e d g l u c o s i d e d i s a c c h a r i d e s by the Koenigs-Knorr  condensation must be c o n s i d e r e d i m p r a c t i c a l .  I n v e r s i o n at Carbon Atom 2 An i n t e r e s t i n g approach  to oC-glue opyrano s i d e s  r e p o r t e d e a r l y t h i s year (13).  An attempt was  was  made to  r e p l a c e i o d i d e i n a l k y l 2-deoxy-2-iodo-o£ -D-mannopyranoside t r i a c e t a t e s with a c e t a t e . to be r e a d i l y prepared.  The iodo compound i s r e p o r t e d  Thus a Sjj.g> replacement  of iodo  by a c e t a t e would r e s u l t i n an o C - g l u c o p y r a n o s y l c o n f i g u r a t i o n . U n f o r t u n a t e l y , the i o d i d e was n u c l e o p h i l i c a t t a c k on  found h i g h l y r e s i s t a n t to  carbon.  Condensation V i a 1,2-Anhydro Rings A l c o h o l y s i s of  tri-O-acetyl-l,2-anhydro-pC-D-glucopyranose  ( B r i g l ' s anhydride) a t room temperature produce /3 - g l u c o s i d e s i n good y i e l d  has been shown to  (14, 15).  However, the  s t e r i c outcome of the r e a c t i o n i s changed i f the r e a c t i o n i s c a r r i e d out a t e l e v a t e d temperatures.  The r e a c t i o n of phenol  with B r i g l ' s anhydride at 100° y i e l d e d o n l y phenyl 3,4,6tri-0-acetyl-o£-D-glucopyranoside  (14),  Lemieux  (16)  v i s u a l i z e s the r e a c t i o n as proceeding through a 1,6-^3-D- c y c l i c ion which i s capable of r e a c t i n g a t carbon atom one to form  -6  the <?C - g l u c o s i d e , Haworth and Hickinbottom B r i g l ' s anhydride Condensation  (17) were the f i r s t  to u t i l i z e  i n the s y n t h e s i s of d i s a c c h a r i d e s .  of t h i s anhydride  with  2,3,4,6-tetra-0-acetyl-  ytf-D-glucose i n benzene at 90-100° gave an e i g h t percent y i e l d of oC ,  j3-trehalose.  In a s i m i l a r manner, Lemieux (18, 19) has s y n t h e s i z i n g maltose o c t a a c e t a t e and condensation  of B r i g l ' s anhydride  succeeded i n  sucrose o c t a a c e t a t e  by  with l , 2 , 3 , 6 - t e t r a - 0 - a c e t y l -  /3-D-glucopyranose and 1,3,4,6-te tra-0-acetyl-|S-D-f r u c t o s e respectively.  The  s y n t h e s i s of sucrose, although  r e p o r t e d by P i c t e t and Vogel  erroneously  (20, 21), had not been p r e v i o u s l y  accomplished. K o j i b i o s e was B r i g l ' s anhydride  i s o l a t e d from a mixture  o b t a i n e d by h e a t i n g  at 116° f o r s e v e r a l days (22).  d i s a c c h a r i d e products were p r e s e n t , one  of which  Two  other  was  c h r o m a t o g r a p h i c a l l y i d e n t i c a l to o£ , c<-trehalose. Condensations temperatures  with B r i g l ' s anhydride  at elevated  give products i n which the oC-isomer predominates.  U n f o r t u n a t e l y , s i d e r e a c t i o n s such as s e l f - c o n d e n s a t i o n of the anhydride  are known to occur under these c o n d i t i o n s .  a r e s u l t , i n a l l cases s t u d i e d , the y i e l d s of d i s a c c h a r i d e were  low.  As  -7-  Anomerization The  anomerization  of a l k y l g l y c o s i d e s was  by Pacsu (23) i n 1928.  Refluxing  first  s o l u t i o n s of  c h l o r i d e or t i t a n i u m t e t r a c h l o r i d e converted  reported  stannic  methyl  O - a c e t y l - j3 -D-glucopyranoside i n t o the corresponding  tetraoC-anoraer.  Although v a r i e d o p i n i o n s e x i s t as to the mechanism of t h i s r e a c t i o n , Lindberg  (24) and Lemieux (25) have shown that  the g l y c o s i d i c l i n k a g e i s not completely anomerization.  Lemieux (16) has  p o s t u l a t e d by Lindberg  broken during  discussed  (24), and has  the  the mechanism  suggested an a l t e r n a t e  mechanism which he f e e l s meets fewer o b j e c t i o n s . A r e f l u x i n g s o l u t i o n of t i t a n i u m t e t r a c h l o r i d e i n chloroform  anomerized g e n t i o b i o s e  anomer, isomaltose pentachloride of the  (26).  octaacetate  to the  oC-  A s i m i l a r r e a c t i o n using antimony  as the c a t a l y s t gave y i e l d s of one  h a l f that  t i t a n i u m t e t r a c h l o r i d e c a t a l y s i s (27).  A unique combination of r e a c t i o n s , i n c l u d i n g  anomerization,  l e d to the s y n t h e s i s of 6-0-(oC-D-glucopyranosyl)-D-galactose (28).  A Koenigs-Knorr condensation of tetra-O-acetyl-OC-D-  glucopyranosyl  bromide and  gave o n l y the j3 - 1 , 6 - l i n k e d of the d i s a c c h a r i d e  1,2:3,4-diisopropylidene disaccharide.  octaacetate  galactose  Anomerization  with t i t a n i u m t e t r a c h l o r i d e  y i e l d e d an e q u i l i b r i u m mixture of the oL - and & - g l y c o s i d i c  -8-  forms.  D e - O - a c e t y l a t i o n and  ^-glucosidase  left  o n l y the  Anomerization has of  ai.-disaccharides  that recent not  d i g e s t i o n of the mixture with  not been w i d e l y used i n the  f o r two  extension  c^-l,6-disaccharide.  reasons.  allowed time f o r the f u l l u t i l i z a t i o n reaction  disaccharides  i n which the  hydroxyl.  It i s possible  developed.  Modification  to  g l y c o s i d i c bond i s to a primary t h a t new  catalysts for  the  l i n k e d i n secondary p o s i t i o n s  Such an advancement would enable  to d i f f i c u l t i e s i n v o l v e d i n the  o^-glucosyl-disaccharides  sugar u n i t r e q u i r e  means of a c h i e v i n g of b l o c k i n g  synthesis  of  cC-  the p o s s i b i l i t y of modifying n a t u r a l l y  M o d i f i c a t i o n s which allow  The  of t h i s procedure.  Reactions  disaccharides, occurring  has  of a l l types of oC - d i s a c c h a r i d e s .  preparation  Due  of these i s  seems g e n e r a l l y a p p l i c a b l e o n l y  anomerization of d i s a c c h a r i d e s w i l l be  first  of anomerization to d i s a c c h a r i d e s  Secondly, the  the  The  synthesis  the  was  investigated.  a l t e r a t i o n of a p o s i t i o n on  the r e a c t i o n to be  specific.  The  t h i s s p e c i f i c i t y u s u a l l y r e q u i r e s the  use  groups on a l l p o s i t i o n s where r e a c t i o n i s u n d e s i r e d .  j u d i c i o u s choice  of b l o c k i n g  groups may  p r e f e r e n t i a l removal, thus p e r m i t t i n g r e a c t i o n s to be  allow  a s e r i e s of  their consecutive  c a r r i e d out on d i f f e r e n t p o s i t i o n s .  f o l l o w i n g d i s c u s s i o n o u t l i n e s the  d i f f e r e n t types of  The blocking  groups and  describes  disaccharide  their synthetic applications i n  chemistry.  P r o t e c t i o n of the Reducing The  reducing  Function  f u n c t i o n of a d i s a c c h a r i d e  u s u a l l y e x i s t i n g i n a hemiacetal form. of o x i d a t i o n and  reduction  Chemically,  f u n c t i o n can be  aldehyde or hemiacetal d e r i v a t i v e s . r i n g s t r u c t u r e of the  blocking  described  The  as e i t h e r  l a t t e r r e t a i n s the  sugar, whereas the former opens the  r i n g to give an a c y c l i c placed  extreme ease  of t h i s group n e c e s s i t a t e s i t s  p r o t e c t i o n during most r e a c t i o n s . groups f o r the r e d u c i n g  The  i s an aldehyde  derivative.  Emphasis w i l l not  on t h i s d i s t i n c t i o n however, since the  p r o p e r t i e s of the members w i t h i n these two  be  chemical  groups vary  so  widely. The  benzyl  group has been most f r e q u e n t l y used i n s y n t h e t i c  a l t e r a t i o n s of d i s a c c h a r i d e s because of i t s s t a b i l i t y ease of removal.  B e n z y l g l y c o s i d e s are base s t a b l e  r e s i s t a n t to m i l d l y a c i d i c c o n d i t i o n s . g l y c o s i d e i s g e n e r a l l y achieved  Synthesis  of  and  and the  by Koenigs-Knorr condensation  and removal i s e a s i l y accomplished by hydrogenation under mild conditions.  In h i s s t u d i e s on the p a r t i a l l y methylated  d e r i v a t i v e s of maltose and group to b l o c k the r e d u c i n g obtained  very  c e l l o b i o s e (29), Hess used the function.  Jayme and  Demmig  benzyl (30)  c e l l o b i o u r o n i c a c i d , 4-0-(£ -B-glucopyranosyl u r o n i c  -10-  acid)-D-glucose,  by c a t a l y t i c  c e l l o b i o s i d e and  subsequent cleavage of the  Kremer and  o x i d a t i o n of b e n z y l ( 5 -  Gundlach (31) used b e n z y l  glycoside.  ^-maltoside  as  starting  m a t e r i a l i n the s y n t h e s i s of a branched t e t r a s a c c h a r i d e . Although a great v a r i e t y of other  g l y c o s i d e s of  have been prepared (see f o r example 32), few as s y n t h e t i c i n t e r m e d i a t e s .  to the  and  disaccharide linkages.  have been used  Workers have g e n e r a l l y regarded  g l y c o s i d e s such as methyl b i o s i d e s as poor due  disaccharides  intermediates,  s i m i l a r i t y i n ease of h y d r o l y s i s of the g l y c o s i d i c  t h a t a c e t o l y s i s of the  Compton (33) has  shown, however,  g l y c o s i d e i s c o n s i d e r a b l y f a s t e r than  the cleavage of the d i s a c c h a r i d e .  The  s y n t h e s i s of  cello-  biomethylose  (4-0-(6-deoxy--D-glucopyranosyl)-6-deoxy-glucose)  was  i n good y i e l d from the a c e t o l y s i s of the methyl  achieved  ^3-glycoside  (33).  Other than t h i s s y n t h e s i s and  t h a t of  sophorose ( 2 - 0 - ( ^ -D-glucopyranosyl)-D-glucose) (34), a c e t o l y s i s has been d i s r e g a r d e d  i n s y n t h e t i c procedures.  Caution  be employed when the r e a c t i o n i s to be a p p l i e d to l i n k e d i n the primary p o s i t i o n , i . e . 1 — 6 ,  should  disaccharides  as Matsuda  and  co-workers (35) have shown t h a t d i s a c c h a r i d e s with 1 — 2 , and  1—4  1—3,  l i n k a g e s are c o n s i d e r a b l y more s t a b l e to a c e t o l y s i s  than are 1 — 6  linkages.  A l k a l i n e degradation  of a r y l b i o s i d e s has been shown to  y i e l d 1,6-anhydro r i n g s (36), which may  be  then  hydrolyzed  -11-  under weakly a c i d i c c o n d i t i o n s to give the parent  sugars.  At p r e s e n t , no s y n t h e t i c route has u t i l i z e d the a r y l g l y c o s i d e as a b l o c k i n g group with removal v i a the anhydro Two  important  syntheses have proceeded  b l o c k e d with a 1,6-anhydro r i n g .  sugar.  from a d i s a c c h a r i d e  1,6-Anhydro-^3-cellobiose  has been the s t a r t i n g m a t e r i a l f o r the s y n t h e s i s of both cellobiouronic acid 4-G-(  (37) and p s e u d o - c e l l o b i o u r o n i c a c i d ,  -D-glucopyranosyl)-D-glucuronic The 1,6-anhydride of maltose  was  acid first  (38). r e p o r t e d by P i c t e t  and M a r f o r t (39) as a product of the thermal decomposition maltose.  Karrer and Kamienski (40) l a t e r r e p o r t e d i t s s y n t h e s i s  from the base e l i m i n a t i o n of the methiodide amino h e p t a - 0 - a c e t y l - ^ 3 - m a l t o s i d e . s y n t h e s i z e d the hexaacetate hepta-0-acetyl-^3 - m a l t o s i d e . maltose  of  was  of N,N-dimethyl-  Asp and Lindberg  (41)  by a base e l i m i n a t i o n of phenyl A c e t o l y s i s of  f i r s t r e p o r t e d by Freudenberg  l,6-anhydro-|S-  and S o f f (48).  authors showed t h a t the anhydro l i n k a g e was  These  c l e a v e d much  f a s t e r than the d i s a c c h a r i d e l i n k a g e . It  should be noted t h a t although a n i l i d e s (43)  d i t h i o a c e t a l s (44, 45) of d i s a c c h a r i d e s have been  and  prepared,  these d e r i v a t i v e s have not been used as s y n t h e t i c i n t e r m e d i a t e s . There e x i s t s an ample s e l e c t i o n of g l y c o s i d i c b l o c k i n g groups t h a t can be removed under a v a r i e t y of  experimental  -12  conditions.  J u d i c i o u s choice of these b l o c k i n g agents  the r e a c t i o n of other p o r t i o n s of the molecule d e s t r u c t i o n of the r e d u c i n g  permits  without  group.  Use of Anhydro Rings Anhydro d e r i v a t i v e s may be u s e f u l as b l o c k i n g groups as w e l l as r e a c t i v e c e n t e r s .  The opening of a c e t y l a t e d 1,6-  anhydrides with t i t a n i u m t e t r a c h l o r i d e c h l o r i n a t e s on the C - l p o s i t i o n , g i v i n g an <^-chloride with a f r e e C-6 h y d r o x y l (46).  Opening of ethylene oxide type anhydro r i n g s can be  accomplished  with a v a r i e t y of r e a g e n t s .  The c h e m i s t r y of  the anhydro sugars was reviewed i n 1946 by Peat  (47) and more  r e c e n t l y by Newth ( 4 8 ) . The  s y n t h e s i s of 1,6-anhydro- ^ - m a l t o s e  (41) was d e s c r i b e d  e a r l i e r i n the d i s c u s s i o n on b l o c k i n g groups f o r the r e d u c i n g function. maltose  Formation  of 1,2,2»,3,3',4 ,6•-hepta-0-acetyl-^3 1  through opening of the anhydride with t i t a n i u m  t e t r a c h l o r i d e , and subsequent  r e a c t i o n of the c h l o r i d e with  mercuric a c e t a t e has l e d to the s y n t h e s i s of branched  tri-  s a c c h a r i d e s (41, 4 9 ) . Methyl 5,6 1 3 ,6 ' -di-anhydro-/3-maltoside 1  and / 3 - c e l l o b i o s i d e  have been prepared by the a c t i o n of base on t h e i r d i - m e s y l a t e s (50).  In s p i t e o f the i n t e r e s t i n g r e a c t i o n s undergone by  3,6-anhydrides,  t h e i r use i n the s y n t h e s i s of m o d i f i e d  -13-  disaccharides i s severely r e s t r i c t e d .  The  opening of  the  anhydride r e q u i r e s c o n d i t i o n s so severe t h a t cleavage of d i s a c c h a r i d e would s u r e l y r e s u l t The  s y n t h e s i s of ethylene  disaccharide  s e r i e s may  (51,  oxide  provide  the  52). type r i n g s i n the  a route  for configurational  change i n the c o n s t i t u e n t monosaccharides, e s p e c i a l l y those on the non-reducing p o r t i o n of the molecule.  Such syntheses  must await the f r e e i n g of a s p e c i f i c hydroxyl  within  molecule, as the anhydride i s u s u a l l y prepared by of a s u l p h o n y l Use  e s t e r with  the  treatment  alkali.  of E s t e r s  There e x i s t many examples of the use  of a c e t a t e s  b l o c k i n g groups i n d i s a c c h a r i d e i n v e s t i g a t i o n s . examples have a l r e a d y been d e s c r i b e d .  Two  as  Three such  of these i n v o l v e d  the opening of f u l l y a c e t y l a t e d 1,6-anhydro-disaccharides with C-l  titanium t e t r a c h l o r i d e . with mercuric  the molecule. cellobiose glucose The  acetate  l e a v e s o n l y one  This hydroxyl  (38).  Condensation of the h a l i d e at  at C-6  free hydroxyl  has been o x i d i z e d i n  In maltose, i t has been condensed  to give the anomeric t r i s a c c h a r i d e s (41, i s o l a t i o n of primary hydroxyls  been achieved  through t r i t y l a t i o n ,  This s y n t h e t i c route was  in  49).  in disaccharides  a c e t y l a t i o n , and  used i n two  with  syntheses  has  detritylation.  already  -14-  mentioned: the  s y n t h e s i s of c e l l o b i o u r o n i c a c i d (37),  and  a t e t r a s a c c h a r i d e formed from maltose (31).  The  of c y c l o h e x y l 4-0-( o^-D-glucopyranosyluronic  acid)-/-? -D-  glucopyranosiduronic (53).  a c i d v i a this d i t r i t y l  synthesis  ether was  reported  To prepare the 6 , 6 - d i - 0 - t o s y l e s t e r of oC ,oC-trehalose, 1  Bredereck (54) f i r s t prepared In 1923,  B r i g l and  the d i t r i t y l  ether.  M i s t e l e (55) r e p o r t e d t h a t the a c t i o n  of phosphorus p e n t a c h l o r i d e  on octaacetyl-yS -maltose produced  hexa-0-acetyl-2-trichloroacetyl-y8 -maltosyl c h l o r i d e .  No  f u r t h e r work seems to have been r e p o r t e d on t h i s compound which would be expected to undergo r e a c t i o n s s i m i l a r to i t s glucose  analog.  From these r e a c t i o n s , the s y n t h e s i s of the  1,2-anhydro d e r i v a t i v e as w e l l as 1,2',3,3 ,4•,6,6'-hepta1  0-acetyl-o(-maltose.could  be expected.  By the r e a c t i o n of  aqueous sodium acetate with acetobrom sugars, a c e t a t e s the  cx!-series with o n l y the 2 hydroxyl u n s u b s t i t u t e d have  been prepared  (56,  57).  In p a r t i a l l y a c e t y l a t e d sugars,  the m i g r a t i o n  groups occurs r e a d i l y i n d i l u t e base (58). r e p o r t e d to be migration to  of  provide  (59).  of  acetate  Soft glass i s  s u f f i c i e n t l y a l k a l i n e to c a t a l y z e t h i s This rearrangement c o u l d probably be  utilized  d i s a c c h a r i d e s with only the 4' p o s i t i o n f r e e as i s  r e p o r t e d f o r monosaccharide d e r i v a t i v e s (60).  -15  Examples i n the d i s c u s s i o n above have i l l u s t r a t e d use  of a c e t a t e s  as a b l o c k i n g  group only.  been made to i n c l u d e a review of acetate A r t i c l e s on the p r o p e r t i e s and published  (61, 62).  No  attempt  The  has  or benzoate d e r i v a t i v e s .  r e a c t i o n s of e s t e r s have been  General methods f o r the p r e p a r a t i o n  removal of c a r b o x y l i c a c i d e s t e r s have r e c e n t l y been (63).  the  c h e m i s t r y of t r i f l u o r o a c e t a t e e s t e r s as  to carbohydrate c h e m i s t r y has  and  described  applied  been r e c e n t l y reviewed  (64).  Sulphonyl e s t e r s are unique because of t h e i r manner of r e a c t i o n with n u c l e o p h i l e s .  Whereas c a r b o x y l i c a c i d e s t e r s  undergo acyl-oxygen f i s s i o n upon r e a c t i o n , sulphonyl undergo alkyl-oxygen  cleavage.  at the a l k y l carbon causing that  Nucleophilic attack  esters occurs  i n v e r s i o n of c o n f i g u r a t i o n at  center. Reactions of sulphonate e s t e r s of secondary a l c o h o l s  proceed much slower than those of primary. reaction conditions d i d not  Under c l a s s i c a l  ( r e f l u x i n g acetone) secondary e s t e r s  g e n e r a l l y undergo replacement, but with the use  high d i e l e c t r i c a p r o t i c s o l v e n t s used more f r e q u e n t l y .  such r e a c t i o n s have been  A short d i s c u s s i o n of SJJ^  replacements has been p u b l i s h e d  of  recently  sulphonyl  (65).  Replacement of sulphonates with a v a r i e t y of reagents has  l e d to the  synthesis  of s u b s t i t u t e d deoxy sugars.  example, replacement with azide  i o n f o l l o w e d by  For  reduction  -16-  y i e l d s an amine.  Replacement with i o d i d e and  subsequent  r e d u c t i o n g i v e s the u n s u b s t i t u t e d deoxy sugar.  Coupled  with t h e i r a b i l i t y to i n v e r t c o n f i g u r a t i o n s , replacement r e a c t i o n s undergone by sulphonates h o l d u n l i m i t e d p o s s i b i l i t i e s f o r m o d i f i c a t i o n s i n d i s a c c h a r i d e molecules. Although  sulphonates  show some s p e c i f i c i t y i n r e a c t i n g  p r e f e r e n t i a l l y with primary h y d r o x y l s , the presence  of so  many h y d r o x y l groups i n d i s a c c h a r i d e s does not allow s e l e c t i v i t y to be o p e r a t i v e .  In the d i r e c t  of a d i s a c c h a r i d e , a complex mixture  this  esterification  of sulphonates i s o b t a i n e d .  For t h i s reason many workers p r e f e r to i s o l a t e the f r e e primary h y d r o x y l by formation of the t r i t y l e t h e r .  The  6 , 6 ' - d i - O - t o s y l e s t e r of hexa-O-acetyl-</,oC -trehalose 1  prepared i n t h i s manner (54).  was  Replacement of the t o s y l a t e s  with i o d i d e gave the 6,6'-diiodo  compound which upon  with s i l v e r f l u o r i d e i n p y r i d i n e y i e l d e d the  treatment  di-5,6-^-D-  glucopyranoseen. Benzyl h e x a - 0 - a c e t y l - 6 - O - t o s y l - ^ - m a l t o s i d e 1  with sodium i o d i d e i n acetone Reduction  reacted  to give the 6-iodo compound (66).  with Raney n i c k e l reduced and d e a c e t y l a t e d the iodo  a c e t a t e to y i e l d b e n z y l 6 -deoxy- ^ - m a l t o s i d e . 1  was  was  The  latter  not r e a d i l y c l e a v e d by a brewers yeast p r e p a r a t i o n which  r a p i d l y s p l i t benzyl of the 6'-OH  - m a l t o s i d e , i n d i c a t i n g the  i n the enzyme h y d r o l y s i s .  importance  -17-  By treatment of the 6,6'-di-O-mesylates with a l k a l i ,  the  3,6:3',6'-di-anhydro d e r i v a t i v e s of methyl /3 - c e l l o b i o s i d e and  f3 -maltoside were prepared  (50).  Although m e s y l a t i o n  gave a product which c o u l d be r e c r y s t a l l i z e d , the t o s y l a t i o n product was  amorphous.  An e x c e l l e n t review on s u l p h o n y l e s t e r s was Tipson i n 1953  (67).  Due  prepared  to the many advances i n the  the review i s u n f o r t u n a t e l y out of date.  by  field,  In s p i t e of the  e x t e n s i v e use of sulphonates i n r e c e n t monosaccharide c h e m i s t r y , there are few examples of t h e i r use i n the d i s a c c h a r i d e f i e l d . The development of s p e c i f i c a l l y b l o c k e d d i s a c c h a r i d e s w i l l undoubtedly  awaken i n t e r e s t i n such e s t e r s and t h e i r  reactions.  Use of E t h e r s The  g e n e r a l use of e t h e r s as b l o c k i n g groups i s l i m i t e d  by the severe c o n d i t i o n s g e n e r a l l y necessary f o r t h e i r Two  removal.  types of e t h e r s , b e n z y l and t r i t y l , are u s e f u l because  of c h a r a c t e r i s t i c chemical p r o p e r t i e s which allow t h e i r removal  under m i l d c o n d i t i o n s .  hydrogenation  i n the presence  B e n z y l ethers are removed by of a p a l l a d i u m c a t a l y s t .  e t h e r s are removed under weakly a c i d i c c o n d i t i o n s . e t h e r s may  be used advantageously  Trityl  These  i n m o d i f i c a t i o n s of d i s a c c h a r i d e s .  The c h e m i s t r y of the b e n z y l e t h e r s has been reviewed McCloskey (68).  two  by  This a r t i c l e d e s c r i b e s the general methods  -18-  of s y n t h e s i s and the s t a b i l i t y of the e t h e r s to c e r t a i n reagents.  The  s y n t h e s i s of 3-0-benzyl-D-glucose  r e p o r t e d by b e n z y l a t i o n of  has been  1,2:5,6-di-0-isopropylidene-D-  glucose with b e n z y l bromide and s i l v e r oxide.  More r e c e n t l y  (69), b e n z y l a t i o n has been achieved with b e n z y l c h l o r i d e sodium hydride at 130°  (70).  t h i n l a y e r chromatographic  and  This l a t t e r paper d e s c r i b e s a  system f o r these d e r i v a t i v e s , as  w e l l as a spectrophotometric method of determining the number of b e n z y l r e s i d u e s per molecule. of carbohydrate  One  unfortunate p r o p e r t y  b e n z y l e t h e r s seems to be t h e i r r e l u c t a n c e to  crystallize. McCloskey has s t a t e d t h a t b e n z y l a t i o n appears to be somewhat s e l e c t i v e when b e n z y l c h l o r i d e and hydroxide  are employed.  glucopyranose  B e n z y l a t i o n of 1,6-anhydro-^S-D-  under these c o n d i t i o n s gave v a r y i n g y i e l d s of  the 2,4-di-0-benzyl l i k e l y due  potassium  ether.  This ' s e l e c t i v i t y ' i s more  to s t e r i c hindrance  the 1,6-anhydro b r i d g e .  of the a t t a c k i n g s p e c i e s by  Jeanloz  (71) has shown t h a t  sulphonation of 1,6-anhydro-yS -D-glucopyranose a l s o y i e l d s the 2,4-di-0 s u b s t i t u t e d e s t e r .  S e l e c t i v i t y has been shown  i n the p r e p a r a t i o n of  2-0-benzyl-4,5-0-isopropylidene-D-  fucose dimethyl a c e t a l  (72).  through  The  s y n t h e s i s was  the r e a c t i o n of one mole of sodium and  treatment  achieved subsequent  with b e n z y l c h l o r i d e to give a 42$ y i e l d .  This  r e a c t i o n must be c o n s i d e r e d a p r e f e r e n t i a l a l k o x i d e formation  19-  r a t h e r than s e l e c t i v e b e n z y l a t i o n , since the  sodium r e a c t s  p r e f e r e n t i a l l y with the more a c i d i c h y d r o x y l  group a t carbon  two. Benzyl  e t h e r s have not been used to block p o s i t i o n s  other than the r e d u c i n g in  t h i s c a p a c i t y was H e l f e r i c h has  of t r i t y l in  1948,  ethers  function in disaccharides.  Their  use  outlined e a r l i e r .  reviewed the chemistry  (60).  and a p p l i c a t i o n s  Although t h i s review was  published  the b a s i c a p p l i c a t i o n s of t r i t y l ethers have  remained unchanged. worthy of mention.  Two  new  developments, however, are  Synthesis  of d i s a c c h a r i d e s by  Knorr condensations has been achieved  Koenigs-  by In s i t u replacement  of primary t r i t y l e t h e r s using s i l v e r p e r c h l o r a t e as a catalyst. pyranosyl  Thus the r e a c t i o n of tetra-0-acetyl-o£-D-glucobromide with 1 , 2 , 3 , 4 - t e t r a - 0 - a c e t y l - 6 - 0 - t r i t y l -  ^ - D - g l u c o s e i n nitromethane c o n t a i n i n g s i l v e r gave a c e t y l a t e d g e n t i o b i o s e  i n 55-60$ y i e l d  perchlorate  (75).  An attempt to p r e f e r e n t i a l l y remove a primary  trityl  ether i n the presence of a secondary t e t r a h y d r o p y r a n y l in  a s u b s t i t u t e d r i b o f u r a n o s i d e was  circumvent t h i s problem, Khorana and  unsuccessful  (74).  To  co-workers employed  para-methoxy s u b s t i t u t e d t r i t y l e t h e r s . for  ether  They r e p o r t  that  each methoxyl group s u b s t i t u t e d on the t r i t y l r e s i d u e  r a t e of h y d r o l y s i s i n c r e a s e s by a f a c t o r of about 10.  the  Thus  -20  the t r i s u b s t i t u t e d d e r i v a t i v e , t r i - p - a n i s y l m e t h y l  ether,  h y d r o l a s e s about 1000 times as f a s t as the parent t r i p h e n y l methyl d e r i v a t i v e . the in  t r i t y l residue  Introduction  of p - n i t r o groups i n t o  should i n c r e a s e  i t s resistance  comparison w i t h the parent compound.  a trityl  ether  With such s u b s t i t u t i o n ,  o f any a c i d s t a b i l i t y should be a v a i l a b l e .  Examples of the few uses of t r i t y l ethers of d i s a c c h a r i d e s discussion  to h y d r o l y s i s  have been considered  of e s t e r s .  t h e i r a b i l i t y to r e a c t  i n reactions  p r e v i o u s l y under the  T r i t y l e t h e r s ' major c o n t r i b u t i o n i s s e l e c t i v e l y with primary h y d r o x y l s  even i n the presence of a l a r g e number of secondary The  hydroxyls.  r e a c t i o n of maltose with excess t r i t y l c h l o r i d e gave  6 , 6 ' - d i - O - t r i t y l maltose ( 7 5 ) . Recent workers have shown, however, that i n s u f f i c i e n t t r i t y l c h l o r i d e y i e l d s the 6 ' 0 - t r i t y l d e r i v a t i v e ( 7 6 ) . T r i t y l a t i o n may then l e a d to d i f f e r e n t i a t i o n between not only primary and secondary hydroxyls,but a l s o primary h y d r o x y l s of d i f f e r e n t environments. Use  of A c e t a l s and K e t a l s  Acetals  and k e t a l s d i f f e r from other b l o c k i n g  t h a t they b l o c k  two h y d r o x y l groups s i m u l t a n e o u s l y , and the  f o r m a t i o n of the c y c l i c stereochemistry may c o n t a i n  groups i n  s t r u c t u r e i s h i g h l y dependent on the  of the h y d r o x y l groups i n v o l v e d .  The r i n g  5 or 6 members depending on the c o n f i g u r a t i o n of  the h y d r o x y l s and the reagent employed.  Ketones w i l l not  -21  e a s i l y form s i x membered r i n g s due to the 1 , 3 - d i a x i a l  inter-  a c t i o n between the a l k y l of the ketone and the two a x i a l hydrogens of the sugar.  Benzaldehyde p r e f e r s a s i x membered  r i n g where the l a r g e aromatic p o r t i o n can remain e q u a t o r i a l . In such a compound, the conformation of the fused r i n g s can be c o n s i d e r e d bulky  f i x e d s i n c e f l i p p i n g would n e c e s s i t a t e the  aromatic r i n g to assume an a x i a l o r i e n t a t i o n . Few examples e x i s t of the use of a c e t a l s and k e t a l s i n  d i s a c c h a r i d e chemistry.  Sutra condensed acetaldehyde  with  maltose to form a s i r u p y compound which he regarded as a d i O-acetal  ( 7 7 ) . Under the c o n d i t i o n s r e p o r t e d f o r t h i s  condensation, t h i n l a y e r chromatography i n d i c a t e d the formation of f o u r major products ( 7 8 ) . A c r y s t a l l i n e mono-O-benzylidene compound has been r e p o r t e d  to form by condensation of  benzaldehyde with l a c t o s e d i b e n z y l d i t h i o a c e t a l ( 4 4 ) . No s t r u c t u r e was assigned  to t h i s compound.  most a c e t a l s and k e t a l s can be achieved conditions.  The removal of with weakly a c i d i c  The replacement of 1,2-0-isopropylidene  by a c e t o l y s i s has been r e p o r t e d  (79, 80, 81).  groups  Such m i l d  c o n d i t i o n s should enable the removal of these b l o c k i n g groups without damage to the d i s a c c h a r i d e Epimerizations  structure.  and I n v e r s i o n s  In t h e i r review on the s y n t h e s i s of o l i g o s a c c h a r i d e s , Evans, Reynolds, and T a l l e y (4) give a d e s c r i p t i o n of the v a r i o u s  -22-  methods of changing c o n f i g u r a t i o n s w i t h i n the monosaccharide units.  A l l of these methods i n v o l v e change of c o n f i g u r a t i o n  of the C=2  or C-5  hydroxyl  of the r e d u c i n g  sugar.  In a r e c e n t  paper d e s c r i b i n g the i n v e r s i o n of carbohydrates upon a c e t o l y s i s of i s o p r o p y l i d e n e  d e r i v a t i v e s (82), the author i n d i c a t e s the  s i m i l a r i t y of the a c i d induced i n v e r s i o n s to the aluminum c h l o r i d e and  hydrogen f l u o r i d e e p i m e r i z a t i o n s .  Although  a c i d c a t a l y z e d rearrangements of t h i s type are now  more  f u l l y understood (85), no major developments a p p l i c a b l e to disaccharides The  have been r e p o r t e d  since the review was  written.  j u d i c i o u s a p p l i c a t i o n of the r e a c t i o n s d e s c r i b e d  above  w i l l undoubtedly l e a d to the i s o l a t i o n of many important disaccharides. synthesis  Because of the d i f f i c u l t i e s  of glucose d i s a c c h a r i d e s  m o d i f i c a t i o n o f f e r s a p r a c t i c a l and way  of o b t a i n i n g these compounds.  of  i n v o l v e d i n the  ^-configuration,  chemically i n t e r e s t i n g  -23-  METHODS OF SYNTHESIS Maltobiouronic Acid  4-0-(o^-D-Glucopyranosyluronic  Acid)-D-  glucose. Jayme and Demmig (30) s y n t h e s i z e d c e l l o b i o u r o n i c  acid  by c a t a l y t i c a e r i a l o x i d a t i o n of b e n z y l y 3 - c e l l o b i o s i d e .  The  c a t a l y t i c o x i d a t i o n of carbohydrates has r e c e n t l y been reviewed  (84).  The  o x i d a t i o n has been shown to be  o x i d i z i n g primary hydroxyls f a s t e r than secondary, hydroxyls more r a p i d l y than e q u a t o r i a l . mational a n a l y s i s has been developed these p r i n c i p l e s  (85).  and  axial  A system of c o n f o r -  from the a p p l i c a t i o n of  Since c a t a l y t i c  dependent on s t e r e o c h e m i s t r y , i t was  stereospecific,  oxidation i s highly  i n t e r e s t i n g to compare  the o x i d a t i o n product of b e n z y l y_?-maltoside with t h a t of b e n z y l ft - c e l l o b i o s i d e  (Fig. l ) .  Benzyl hepta-O-acetyl-yd?-maltoside  was  s y n t h e s i z e d from  acetobromomaltose (86) and b e n z y l a l c o h o l by the method d e s c r i b e d by H e l f e r i c h a n d Berger with methanolic maltoside acidic  (87).  condensation  Deacetylation  ammonia gave the c r y s t a l l i n e b e n z y l  (88).  C a t a l y t i c o x i d a t i o n gave a mixture  /3of  sugars, which upon e s t e r i f i c a t i o n with diazomethane  and a c e t y l a t i o n gave c r y s t a l l i n e methyl ( b e n z y l hexa-O-acetylP-maltosid)uronate. i n 40$  y i e l d , based  S a p o n i f i c a t i o n was hydroxide  The methyl e s t e r hexaacetate on the b e n z y l  ^-maltoside  was  obtained  consumed.  achieved by warming with aqueous barium  to y i e l d the barium  ( b e n z y l /S - m a l t o s i d ) u r o n a t e .  -24-  -25-  Hydrogenolysis using p a l l a d i u m on barium  sulphate ( 8 9 ) ,  f o l l o w e d by a c i d i f i c a t i o n with Amberlite IR 120 ( H ) y i e l d e d +  maltobiouronic acid.  E s t e r i f i c a t i o n of m a l t o b i o u r o n i c a c i d  with diazomethane, f o l l o w e d by a c e t y l a t i o n with a c e t i c anhydride  i n p y r i d i n e , y i e l d e d the c r y s t a l l i n e methyl e s t e r  heptaacetate• Borohydride  r e d u c t i o n of a sample o f the a c i d , f o l l o w e d  by a c i d h y d r o l y s i s i n d i c a t e d o n l y g l u c u r o n i c a c i d and s o r b i t o l upon paper chromatography.  The s t r u c t u r e of the s y n t h e t i c  uronic a c i d i s t h e r e f o r e 4-0-(oC-B-glucopyranosyluronic  acid)-  D-glucose. The i s o l a t i o n of m a l t o b i o u r o n i c a c i d from the c a t a l y t i c o x i d a t i o n of b e n z y l  ^ - m a l t o s i d e i n d i c a t e s t h a t the d i f f e r e n c e  between the oC - g l u c o s i d i c glucosidic derivative  derivative  ( c e l l o b i o s e ) i s not s u f f i c i e n t t o  change the s i t e of o x i d a t i o n .  The 6 ' - p o s i t i o n i s p r e f e r e n t i a l l y  o x i d i z e d i n both compounds, y i e l d i n g the r e s p e c t i v e a l d o biouronic  acids.  4-0(ol -D-Glucopyranosyluronic Due t o t h e importance  Acid)-D-xylose.  of a l d o b i o u r o n i c a c i d s , e s p e c i a l l y  those c o n t a i n i n g D-glucuronic a c i d and D-xylose, i n s t r u c t u r a l i n v e s t i g a t i o n s o f n a t u r a l p r o d u c t s , the f o l l o w i n g scheme f o r the s y n t h e s i s of 4-0-(oC-D-glucopyranosyluronic x y l o s e was proposed  (Fig. 2).  acid)-D-  Fig.  2  -27  Prolonged  c a t a l y t i c o x i d a t i o n of b e n z y l  /s-maltoside  or  permanganate o x i d a t i o n of b e n z y l 2,2',3,3' ,4-penta-O-acetyl-yS maltoside  should give the d i - u r o n i c a c i d .  Removal of the  b e n z y l g l y c o s i d e by c a t a l y t i c hydrogenation 4-0-(oC-D-glucopyranosyluronic  would r e s u l t i n  acld)-D-glucuronic a c i d .  Treatment of t h i s d i - a c i d with n i c k e l acetate i n p y r i d i n e a t 80° as o u t l i n e d by Z w e i f e l and Deuel (90) should cause d e c a r b o x y l a t i o n of the r e d u c i n g  sugar r e s i d u e , y i e l d i n g  the d e s i r e d compound. The  c r u c i a l step of t h i s s y n t h e t i c route i s the  d e c a r b o x y l a t i o n r e a c t i o n which, although 1956,  has not been u t i l i z e d  since.  f i r s t reported i n  Although hot p y r i d i n e  has been used to e f f e c t rearrangements i n sugars epimers and corresponding  ketoses  to t h e i r  (91), these authors  employed  p y r i d i n e s o l u t i o n s of n i c k e l s a l t s at 80° f o r d e c a r b o x y l a t i o n . S u b s t i t u t i o n of the uronate at C - l as a g l y c o s i d e  prevents  the d e c a r b o x y l a t i o n , but e s t e r i f i c a t i o n of the a c i d i s r e p o r t e d not to hinder the r e a c t i o n . The mechanism of the r e a c t i o n i s suggested  to be a  complexing of the C - l oxygen lone p a i r by the metal i o n employed as a c a t a l y s t  (90).  I t i s then p o s t u l a t e d t h a t  the hydrogen of the C - l hydroxyl can p a r t i c i p a t e i n an e l e c t r o n t r a n s f e r i n which the c a r b o x y l f u n c t i o n i s e l i m i n a t e d .  28  Although Z w e i f e l and Deuel were able to crystalline  L - a r a b i n o s e from the d e c a r b o x y l a t i o n of D -  galacturonic  a c i d , no arabinose was d e t e c t a b l e by paper  chromatography upon r e p e t i t i o n reported conditions.  of t h i s experiment  under  S e v e r a l more attempts to repeat  work were u n s u c c e s s f u l ,  and f o r t h i s reason  s y n t h e s i s of 4 - Q - ( o i - D - g l u c o p y r a n o s y l u r o n i c was  isolate  the  the  this  proposed  acid)-D-xylose  discontinued.  4-0-(6-Amino-6-deoxy-oC-D-glucopyranosyl)-D-glucose. A possible  synthetic  route to 6 *-amino-6•-deoxy-maltose  (4-0-(6-amino-6-deoxy-^-D-glucopyranosyl)-D-glucose) l i n e d below ( F i g . 3 ) . glycoside,  out-  The methyl e s t e r hexaacetate b e n z y l  an i n t e r m e d i a t e  i n the  s y n t h e s i s of m a l t o b i o u r o n i c  a c i d , upon treatment with methanolic and form the amide.  is  ammonia would d e a c e t y l a t e  Reduction of the amide with l i t h i u m  0  Fig.  3  -50  aluminum hydride would give the primary amine (92), from which the amino sugar c o u l d be i s o l a t e d by  catalytic  debenzylation. Although b e n z y l ethers are s t a b l e to l i t h i u m aluminum hydride under moderate c o n d i t i o n s (95), the r e a c t i o n of b e n z y l g l y c o s i d e s under s i m i l a r c o n d i t i o n s has not been investigated.  For t h i s r e a s o n , the a c t i o n of l i t h i u m  aluminum hydride i n r e f l u x i n g ether on b e n z y l |8-maltoside  was  investigated.  hepta-O-acetyl-  A c e t y l a t i o n of the r e a c t i o n  product a f t e r one hour y i e l d e d m a t e r i a l which i n d i c a t e d  two  major components on s i l i c a g e l t h i n l a y e r chromatography (94). The f a s t e r spot corresponded  to the s t a r t i n g m a t e r i a l , b e n z y l  hepta-O-acetyl-|3-maltoside,  and the slower  presumably n o n a - O - a c e t y l - m a l t i t o l .  spot  The presence  was of compounds  other than b e n z y l h e p t a - O - a c e t y l - |3 -maltoside i n d i c a t e d t h a t the b e n z y l g l y c o s i d e was  unstable to c o n d i t i o n s necessary  f o r the r e d u c t i o n of the amide. route was  For t h i s r e a s o n , t h i s s y n t h e t i c  not c o n s i d e r e d p r a c t i c a l and was  abandoned.  An a l t e r n a t e r o u t e f o r the s y n t h e s i s of 6'-amino-6 f  deoxy-maltose i s the azide replacement ester.  Reduction  of a primary azide y i e l d s a primary amine.  1,6-Anhydro- |S-maltose was I t was  of a 6'-O-sulphonate  s e l e c t e d as the s t a r t i n g m a t e r i a l .  hoped that t o s y l a t i o n of t h i s m a t e r i a l would give  p r e f e r e n t i a l l y the 6'-O-tosylate.  Unfortunately t o s y l chloride  Fig, 4  -32-  was  not s u f f i c i e n t l y s p e c i f i c and t h i n l a y e r  chromatography  i n d i c a t e d two monotosylates and s e v e r a l d i t o s y l a t e s i n a d d i t i o n to s t a r t i n g m a t e r i a l .  T r i t y l a t i o n f o l l o w e d by a c e t y l a t i o n  and d e t r i t y l a t i o n with 80$ a c e t i c a c i d gave 2,2*,3,3',4'p e n t a - 0 - a c e t y l - l , 6 - a n h y d r o - p -maltose. s u b s t r a t e was  T o s y l a t i o n of t h i s  then c a r r i e d out q u i c k l y and i n good y i e l d  the use of excess t o s y l c h l o r i d e . t o s y l e s t e r was  Replacement of the  accomplished by h e a t i n g the e s t e r with  azide i n N,N-dimethylformamide.  by  sodium  D e a c e t y l a t i o n f o l l o w e d by  c a t a l y t i c r e d u c t i o n y i e l d e d c h r o m a t o g r a p h i c a l l y pure araino-l,6-anhydro-6'-deoxy-p -maltose.  6'-  The a b i l i t y of the  6-amino group to hinder a c i d h y d r o l y s i s (95) would be expected to s t a b i l i z e the g l y c o s i d i c l i n k a g e of a 6-amino g l u c o s i d e . This has, i n f a c t , been r e p o r t e d by Cramer and co-workers  (96).  Thus m i l d a c i d h y d r o l y s i s should open the 1,6-anhydro r i n g without cleavage of the d i s a c c h a r i d e , y i e l d i n g 6'-amino-6*deoxy-maltose. 4-0-(6-Deoxy-6-mereapto-ol-D-glucopyranosyl)-D-glucose The replacement of s u l p h o n y l e s t e r s by potassium was  thiolacetate  i n v e s t i g a t e d by Chapman and Owen (97) and found to be a  convenient method of i n t r o d u c i n g a s u l f h y d r y l group i n t o a molecule.  R e a c t i o n of 2,2» j S ^ , . ' - p e n t a - 0 - a c e t y l - l , 6 - a n h y d r o 1  6 ' - 0 - t o s y l - p -maltose with potassium t h i o l a c e t a t e i n  N,N-  -33-  KSAc DMFA  H S0 2  4  A c 0 , Ac OH 2  CH SAc  CH_OAc  2  ISSaOMe MeOH  Pig.  5  &-  -34-  dimethylformamide  gave  2,2',3,3',4'-penta-0-acetyl-6'-S-  acetyl-l,6-anhydro-/#-maltose i n good y i e l d .  Acetolysis  was used to open the 1,6-anhydro r i n g without cleavage of the d i s a c c h a r i d e l i n k a g e .  D e a c e t y l a t i o n of the o c t a a c e t a t e  y i e l d e d the f r e e t h i o sugar, which o x i d i z e d v e r y r a p i d l y with atmospheric oxygen to give the d i s u l p h i d e .  A d d i t i o n of  excess 2-mercaptoethanol regenerated the 6'-deoxy-6 -mercapto 1  maltose. 4-0-(6-De6xy-g<!-D-glucopyranosyl)-D-glucose Although b e n z y l 6 -deoxy-^3-maltoside 1  had been  synthesiz  (66) f o r enzyme s t u d i e s , the removal of the b e n z y l g l y c o s i d e was not attempted.  An attempt to prepare 6-deoxy-,  deoxy-, and 6,6'-dideoxy-maltose  6'-  v i a t o s y l a t i o n of methyl  ^ - m a l t o s i d e f a i l e d to y i e l d c h a r a c t e r i z a b l e products (98). The s y n t h e s i s of 6 * -deoxy-maltose g l u c o p y r a n o s y l ) - D - g l u c o s e ) was of the 6 - 0 - t o s y l a t e by i o d i d e . 1  the i o d i d e y i e l d e d  attempted by the replacement The c a t a l y t i c r e d u c t i o n of  2,2*,3,3',4*-penta-O-acetyl-1,6-anhydro-  6 ' -deoxy- {$>-maltose. 6'-deoxy-maltose.  (4-0-(6-deoxy-<X^-D-  A c e t o l y s i s and d e a c e t y l a t i o n  yielded  -35-  Fig. 6  -36-  4-0-(5-AmiDO-3-deoxy-o<-D-glycopyranosyl)-D-glucose A general s y n t h e s i s of 3-amino-3-deoxy-sugars was  first  i n t r o d u c e d t o carbohydrate chemistry by Baer and F i s c h e r (99) and has been i n v e s t i g a t e d i n a very thorough manner by Baer i n subsequent  p u b l i c a t i o n s (100).  r e c e n t l y reviewed by L i c h t e n t h a l e r  The s u b j e c t has been  (101).  The s y n t h e s i s i s  a m o d i f i c a t i o n of the Sowden-Fischer s y n t h e s i s i n which two aldehyde  groups w i t h i n the same molecule r e a c t with  methane i n a t y p i c a l a l d o l condensation. i s produced  nitro-  The dialdehyde  from g l y c o l o x i d a t i o n with p e r i o d a t e or l e a d  tetraacetate  ( F i g . 7).  nitromethane  under the i n f l u e n c e of base l e a d s to a C - n i t r o  alcohol.  Condensation  Upon a c i d i f i c a t i o n , the n i t r o group i n v a r i a b l y  takes up an e q u a t o r i a l o r i e n t a t i o n . carbons  of the dialdehyde with  The c o n f i g u r a t i o n s o f  2 and 4 can give r i s e to f o u r p o s s i b l e isomers but  i n p r a c t i c e , manipulation of the condensation c o n d i t i o n s allows the p r e f e r e n t i a l formation of c e r t a i n of the c o n f i g u r a t i o n s . Subsequent r e d u c t i o n of the C - n i t r o - a l c o h o l y i e l d s the 3-amino3-deoxy-glycoside. Recent  n u c l e a r magnetic  resonance  work (102) has shown  2!,3 4-tri-0-acetyl-l,6-anhydro-^-D-glucose e x i s t s p r i m a r i l y f  i n a IC r a t h e r than a 3B conformation.  that  -37  -38-  AcO OF\c  0(\c  3B  IC  Replacement of the r e l a t i v e l y b u l k y a c e t y l groups with hydrogen, would s t a b i l i z e the IC conformation as there would be l e s s crowding  of the a x i a l C3 s u b s t i t u e n t a g a i n s t the 1,6-  anhydro b r i d g e and l e s s C2, C4 1 , 3 - d i a x i a l i n t e r a c t i o n . 1,6-Anhydro-^-D-glucose would be expected then, to possess the IC conformation. Reeves (103) has deduced from the o p t i c a l r o t a t i o n of cuprammonium s o l u t i o n s of l,6rra"nhydro-y5 -D-glucose sugar does indeed e x i s t i n a IC conformation. little  t h a t the  There i s  d i f f e r e n c e i n the o p t i c a l r o t a t i o n of the complex  formed from e i t h e r l,6-anhydro-3-0-methyl- ^-D-glucose or /  i t s parent 1,6-anhydro-^-D-glucose.  This i n d i c a t e s t h a t  h y d r o x y l groups 2 and 4 are i n v o l v e d i n the complex formation which they c o u l d o n l y do i f they are i n a d i a x i a l conformation.  ( i . e . IC)  1 , 2 - B i o l s are o x i d a t i v e l y c l e a v e d by l e a d at a r a t e which i s dependent system  (104).  tetraacetate  upon the geometry of the  The c l o s e r the two hydroxyl groups  each other the f a s t e r the r a t e of o x i d a t i o n .  diol  approach  For example,  c i s - c y c l o h e x a n d i o l i s o x i d i z e d 23 times more q u i c k l y than t r a n s - c y c l o h e x a n d i o l (105) and 1,6-anhydro- /3 -D-glucofuranose i s not a t t a c k e d at a l l (106).  In the l a t t e r the 1 , 2 - d i o l  system i s l o c k e d and the p r o j e c t e d bond angle between the hydroxyl groups i s very near 120°. From the i n f o r m a t i o n d i s c u s s e d above, a s y n t h e s i s of 4-0-(3-amino=3-deoxy-o(-D-glycopyranosyl)-D-glucose proposed  ( F i g . 8).  was  Lead t e t r a a c e t a t e o x i d a t i o n a t 5° of  1,6-anhydro^ f& -maltose prepared by d e a c e t y l a t i o n of the known hexaacetate (41), should give the d i a l d e h y d e , as the h y d r o x y l groups on the non-reducing r e s i d u e being t r a n s d i e q u a t o r i a l should o x i d i z e more q u i c k l y than the t r a n s d i a x i a l o r i e n t a t i o n of h y d r o x y l s on the anhydro p o r t i o n of the molecule  glucose  ( F i g . 9).  Condensation of the dialdehyde with nitromethane then give a C-3'  n i t r o - d i s a c c h a r i d e which a f t e r  would  reduction  c o u l d be hydrogenolyzed to the f r e e amino sugar. Before attempting the t e t r a a c e t a t e o x i d a t i o n of anhydro- ^ - m a l t o s e , the o x i d a t i o n of model compounds attempted.  1,6was  The two compounds s e l e c t e d as models of both  -41-  p o r t i o n s of the 1,6-anhydro- p-maltose molecule were methyl O^-D-glucoside and I t was  rather  l,6-anhydro-^_? -D-glucose ( F i g . 9  ).  s u r p r i s i n g , t h e r e f o r e , to f i n d t h a t  1,6-  anhydro- fZ -D-glucose o x i d i z e d at a f a s t e r r a t e than methyl o_-D-glucoside ( F i g . 10).  From c o n s i d e r a t i o n  of  the  e x i s t i n g data o u t l i n e d above, 1,6-anhydro-y_?-D-glucose would be expected to o x i d i z e at ^ / ^ Q or l e s s the r a t e of methyl  oL-D-glucoside hydroxyl  due  groups.  to the o r i e n t a t i o n s of the Such i s not  the case, i n f a c t , the  molecules o x i d i z e at e s s e n t i a l l y the Three p o s s i b i l i t i e s allow  respective two  same r a t e .  explanation  of the  oxidation  results; a) Lead t e t r a a c e t a t e o x i d a t i o n i s not o x i d i z e s g l y c o l groups without regard  specific  and  to t h e i r geometry.  While t h i s p o s s i b i l i t y must be kept i n mind i t i s extremely unlikely.  The  b a s i s f o r the use  of l e a d t e t r a a c e t a t e  has  depended on the s p e c i f i c i t y of i t s o x i d a t i v e cleavage  and  i t i s d i f f i c u l t to see why pose an b)  l,6-anhydro-y3-D-glucose  exception. The  1,6-anhydro-linkage i s hydrolyzed  g l a c i a l a c e t i c a c i d , which i s the tetraacetate oxidations, then be  should  attacked  very q u i c k l y i n  s o l v e n t used f o r l e a d  g i v i n g D-glucose.  very q u i c k l y by the oxidant  D-Glucose would with a t o t a l  Catalyzed  Lead Tetraacetate  Oxidation  -44-  r a t e f o r the the  two  glycoside.  observing  the  |S-C-glucose occurred  reactions  s l i g h t l y greater  than the r a t e f o r  This a t t r a c t i v e p o s s i b i l i t y was  eliminated  by  o p t i c a l r o t a t i o n of a s o l u t i o n of 1,6-anhydroin glacial acetic acid.  I f any  hydrolysis  the r o t a t i o n would change from a s t r o n g l y negative  value ( c a . -70°)  to a p o s i t i v e value ( c a .  +53°).  In  24  hours no change i n r o t a t i o n of the l e v o r o t a t o r y s o l u t i o n  was  observed. c) l,6-Anhydro-/5-D-glucose i n g l a c i a l a c e t i c a c i d a c t u a l l y e x i s t s i n a 3B conformation. tetraacetate of methyl  oxidation  Such a conformation would  to proceed at a r a t e equal to  o(-D-glucopyranoside.  of o x i d a t i o n  of the  glucoside  The  may  allow  that  s l i g h t l y slower r a t e  p o s s i b l y be e x p l a i n e d  by  the f o r m a t i o n of a 6-0-formyl e s t e r which slows the r a t e oxidation  of formic  a c i d to carbon d i o x i d e .  This  esterification  cannot occur i n 1,6-anhydro-^-D-glucose because the linkage blocks  the  6-position.  s o l v e n t i s not  a common occurrence but  has been observed i n However, i n these  compounds, the r i n g remains i n a c h a i r with o n l y  The  substituents  proposed s y n t h e s i s  discontinued  anhydro  Change i n conformation with  methyl 2-deoxy- c/-D-ribopyranoside (107).  d i s p o s i t i o n of the  the  varying.  of the amino d i s a c c h a r i d e  at t h i s p o i n t due  of  to the  l a c k of  was  information  -45-  on the o x i d a t i o n step.  F u r t h e r work i s to be c a r r i e d out i n  an e f f o r t to determine the cause of the anomalous o x i d a t i v e behaviour  of l,6-anhydro-/3-D-glucose.  Attempts to Synthesize  4-0-( oC -D-Glucopyranosyl)-6-deoxy-6-  substituted-D-glucose D e r i v a t i v e s In an attempt to s y n t h e s i z e 6 - s u b s t i t u t e d d e r i v a t i v e s of maltose,  b e n z y l 4 *,6 -O-benzylidene-j5 -maltoside was  employed.  1  In t h i s molecule  o n l y one primary hydroxyl remains f r e e and  attempts to s e l e c t i v e l y t o s y l a t e t h i s hydroxyl group were unsuccessful.  The  r e a c t i o n of a more s p e c i f i c  trityl  c h l o r i d e , was  investigated.  trityl  i n the presence  Although removal of  of benzylidene would not have been  p o s s i b l e , the use of a trimethoxy  t r i t y l derivative  have p e r m i t t e d such a m a n i p u l a t i o n . in  reagent,  Had  (74) would  tritylation  proceeded  a normal f a s h i o n , the corresponding methoxy d e r i v a t i v e  would have been prepared. p o s i t i o n was  not achieved.  t r i t y l c h l o r i d e may  S p e c i f i c t r i t y l a t i o n of the The l a c k of r e a c t i o n of the  have been due  t h i s reason mesylation was  to s t e r i c hindrance  attempted.  M e s y l a t i o n was  most e f f e c t i v e of the three methods t r i e d . r e a c t i o n was  6-  and f o r the  However, the  abandoned as a p r e p a r a t i v e method, because  sulphonation o c c u r r e d i n only about 50$ y i e l d as i n d i c a t e d by t h i n l a y e r chromatography.  -46-  BISCUSSION Maltobiouronic Acid The s y n t h e s i s of m a l t o b i o u r o n i c a c i d by the c a t a l y t i c o x i d a t i o n of b e n z y l |3 -maltoside was accomplished i n advance of t h i s work by Hirasaka (108).  slightly  Knowledge  of h i s  r e s u l t s was obtained s h o r t l y a f t e r p u b l i c a t i o n of our work e a r l y t h i s year  (109).  The p h y s i c a l constants of a l l  compounds common to both p u b l i c a t i o n s were i n agreement. Hirasaka  (110)  r e p o r t e d , a t the same time, the s y n t h e s i s  of m a l t o b i o u r o n i c a c i d by the permanganate 2' ,3,3 ,4* , 6 - h e p t a - 0 - a c e t y l - [3 -maltose. 1  o x i d a t i o n of 1,2,  This acetate was  also  t r e a t e d i n a c e t i c a c i d with chromium t r i o x i d e f o l l o w e d by permanganate.  A c i d chrornate o x i d a t i o n of the a l c o h o l i s  presumably f a s t e r than permanganate, whereas the r e v e r s e i s true of the o x i d a t i o n of the aldehyde. a f a s t e r o v e r a l l o x i d a t i o n was  By u s i n g both  reagents  accomplished.  M a l t o b i o u r o n i c a c i d would be expected  to be one of the  products obtained from the p a r t i a l a c i d h y d r o l y s i s of o x i d i z e d amylose.  P a r t i a l l y a c e t y l a t e d amylose was prepared from  amylose by t r . i t y l a t i o n , a c e t y l a t i o n and d e t r i t y l a t i o n .  Chromate-  permanganate o x i d a t i o n of t h i s s u b s t r a t e y i e l d e d m a t e r i a l o x i d i z e d a t 50% of the primary a l c o h o l i c p o s i t i o n s Although  (111).  p a r t i a l h y d r o l y s i s was not r e p o r t e d , the authors  -47-  s t a t e d that the o x i d i z e d amylose had p h y s i c a l constants q u i t e d i f f e r e n t from n i t r i c a c i d o x i d i z e d amylose. The non-reducing r e s i d u e i n maltose has been assigned both skew (112) and c h a i r (113) conformations by v a r i o u s authors.  Had c a t a l y t i c o x i d a t i o n of b e n z y l  ^ - m a l t o s i d e given  a major product other than m a l t o b i o u r o n i c a c i d , a conformation might have been assigned to the s t a r t i n g m a t e r i a l .  With  the i s o l a t i o n of m a l t o b i o u r o n i c a c i d as the major product nothing can be s a i d r e g a r d i n g the conformation of b e n z y l ^S-maltoside. A c i d H y d r o l y s i s of  1,6-Anhydrides  A c i d h y d r o l y s i s of 1,6-anhydro r i n g s has been r e p o r t e d i n a number of communications (114, 115, 116).  0.2N  H y d r o c h l o r i c a c i d f o r 4 hours on a steam bath (115) the s e v e r i t y of c o n d i t i o n s necessary to e f f e c t hydrolysis. of the 1,4-/2  indicates  this  Under such c o n d i t i o n s the r a t e s of h y d r o l y s i s l i n k a g e and the anhydro r i n g of l,6-anhydro-/3 -  c e l l o b i o s e were found to be n e a r l y equal (116).  In s t u d i e s  of 6-amino-6-deoxy-D-glucose (96), methyl 6-amino-6-deoxyo^-D-glucoside was  not h y d r o l y z e d by 0.2N  a t 100° f o r 8 hours.  hydrochloric  acid  Extending these c o n d i t i o n s to e'-amino-  l,6-anhydro-6'-deoxy-^S-maltose,  the anhydro r i n g should  h y d r o l y z e while the g l y c o s i d i c l i n k a g e should not, because the s t a b i l i z a t i o n by the 6-amino f u n c t i o n .  of  -48-  H y d r o l y s i s of with 0.15N  6 -amino-l,6-anhydro-6•-deoxy-/3 -maltose 1  h y d r o c h l o r i c a c i d f o r 13 hours at 100°  yielded,  as i n d i c a t e d by paper chromatography, glucose, the  expected  amino d i s a c c h a r i d e , some degradation p r o d u c t s , and a small amount of s t a r t i n g m a t e r i a l . somewhat mysterious  The presence  of glucose  was  as there d i d not appear to be an equal  amount of 6-amino-6-deoxy-glucose present i n the h y d r o l y s a t e . The r e l u c t a n c e of the anhydro r i n g to open may  be a f u r t h e r  example of the d i f f i c u l t y with which amino sugars are h y d r o l y z e d (95).  This i s probably due to the n e c e s s i t y of  double p r o t o n a t i o n f o r h y d r o l y s i s , as the amine r e a d i l y accepts the i n i t i a l proton and f u r t h e r p r o t o n a t i o n i s hindered by the molecule's of  p o s i t i v e charge.  The  isolation  a f r a c t i o n r e c o g n i z a b l e as the amino-disaccharide  indicates  a d e f i n i t e s t a b i l i z a t i o n of the g l y c o s i d i c l i n k a g e by the  6-  amino f u n c t i o n . A c e t o l y s i s of 1,6-Anhydrides A c e t o l y s i s of 1,6-anhydro r i n g s was Freudenberg  and S o f f (42).  These authors showed t h a t the  r e a c t i o n gave an e q u i l i b r i u m mixture with the oL predominating  f i r s t r e p o r t e d by  of the  (88$ f o r D-glucose).  and  £  forms  Haskins, Hann  and Hudson showed t h a t the 1,6-anhydro l i n k a g e was  acetolyzed  much f a s t e r than the 1,4-^6 d i s a c c h a r i d e l i n k a g e .  These  procedures  were i n c o r p o r a t e d i n the chemical syntheses  cellobiose  (117) and l a c t o s e (118).  of  -49-  Thin l a y e r chromatography of carbohydrate a c e t a t e s has been d e s c r i b e d by a number of authors (94, 119). attempt  In an  to f o l l o w the a c e t o l y s i s of 1,6-anhydro d e r i v a t i v e s  by t h i n l a y e r chromatography, samples were removed d u r i n g the course of the r e a c t i o n and layer plates. p l a t e was The  thin  The a d d i t i o n of two drops of p y r i d i n e to the  s u f f i c i e n t to  spot was  spotted d i r e c t l y onto  n e u t r a l i z e the s u l p h u r i c a c i d p r e s e n t .  then d r i e d a t room temperature.  The  plates  were developed with e t h y l e t h e r - t o l u e n e (2:1, v/v., s o l v e n t D),  a s o l v e n t d e s c r i b e d by Gee  (120) f o r t h i n  chromatography of f u l l y methylated  sugars.  layer  The a c e t a t e s  were d e t e c t e d by s p r a y i n g with s u l p h u r i c a c i d and h e a t i n g . A t y p i c a l p a t t e r n observed i n the a c e t o l y s i s of  penta-0-  acetyl-6'-S-acetyl-l,6-anhydro-6'-deoxy-jS-maltose  i s shown  i n F i g u r e 11. Obviously, two The f i r s t  consecutive r e a c t i o n s are t a k i n g p l a c e .  i s the a c e t o l y s i s of the anhydro r i n g to an  equal mixture  of the c£ and  /3 a c e t a t e s .  The  second  i s the anomerization of the two a c e t a t e s to give an mixture  i n which the oC predominates.  second r e a c t i o n was  approximately reaction  equilibrium  The i d e n t i t y of the  confirmed by the formation of the  e q u i l i b r i u m mixture upon d i s s o l v i n g i n the a c e t o l y s i s s o l u t i o n .  octa-O-acetyl-yS-maltose  I t i s q u i t e l i k e l y the  opening  of the anhydro r i n g i s i n i t i a t e d by the formation of a  -50-  \  Reaction Time (min.) Fig.  II  -51-  1,6"p  - D - e y c l i c i o n which r e a r r a n g e s to a more s t a b l e  carboniura i o n .  This i o n r e a c t s with a molecule of a c e t i c  a c i d to form an equal mixture of the  and  /3 anomers.  Anomerization, c a t a l y z e d by the s u l p h u r i c a c i d , then  shifts  the r a t i o of isomers to the e q u i l i b r i u m value ( F i g . 12). Mercapto  Sugars  Although the replacement  of sulphonates by  thiolacetate  i s a convenient method of i n t r o d u c i n g sulphur i n t o a sugar, c o m p l i c a t i o n s a r i s e upon d e a c e t y l a t i o n . to undergo atmospheric  T h i o l s are known  o x i d a t i o n and t h i s r e a c t i o n i s  a c c e l e r a t e d i n the presence of a l k a l i . d e a c e t y l a t i o n has been suggested  Acid  catalyzed  (121) but these c o n d i t i o n s  do not seem a d v i s a b l e f o r d i s a c c h a r i d e d e r i v a t i v e s . Regeneration of the t h i o l from the d i s u l p h i d e can be accomplished by a d d i t i o n of excess 2-mercapto-ethanol  (122).  S e v e r a l a l t e r n a t e methods e x i s t f o r the i n t r o d u c t i o n of sulphur i n t o sugar molecules and these have been reviewed Hutson and Horton  (65).  P o s s i b l y the most promising method  i s the replacement  of sulphonates by t h i o s u l p h a t e s forming  the 'Bunte s a l t .  As t h i s molecule now  1  by  possesses a negative  charge, i o n exchange chromatography can be c o n v e n i e n t l y c a r r i e d out.  Generation of the f r e e mercapto sugar i s  accomplished by a d d i t i o n of excess low molecular t h i o l s such as 2-mercapto-ethanol.  weight  The use of t h i o s u l p h a t e  CH OAc  H 0Ac-  2  2  ™ ° 0  PAc-  AcO'X.OAc  H S0 2  AcOH  OAc  4  AcO' X i O A c  H,OAc 'OAc  cI  F i g . 12  -53-  d e r i v a t i v e s was of sulphur  first  i n t r o d u c e d by Swan (122)  f o r the  study  containing proteins.  Comparative R e a c t i v i t y of Primary Hydroxyl Groups As i n v e s t i g a t i o n s on d i s a c c h a r i d e s continue, one becoming apparent.  The  reducing r e s i d u e of 1,4  primary hydroxyl l i n k e d glucose  group on  fact i s  the  disaccharides i s less  r e a c t i v e than the other primary h y d r o x y l . Lindberg  (38) has remarked on the d i f f i c u l t y of o x i d i z i n g  the 6 - p o s i t i o n with r e s p e c t to the 6 ' - p o s i t i o n .  The  partial  t r i t y l a t i o n of maltose g i v e s only the 6 ' - d e r i v a t i v e , and 6 - s u b s t i t u t e d d e r i v a t i v e (110).  C a t a l y t i c o x i d a t i o n of  maltose or c e l l o b i o s e d e r i v a t i v e s l e a d to products  (30, 108,  109).  The  no  6'-oxidized  u n s u c c e s s f u l attempts to  prepare 6 - s u b s t i t u t e d d e r i v a t i v e s as d e s c r i b e d i n t h i s work serve as a d d i t i o n a l examples of what may i n 1,4  linked disaccharides.  be a general  effect  -54-  EXPERIMENTAL Evaporations were c a r r i e d out under reduced pressure at a bath temperature  of 40-45°.  O p t i c a l r o t a t i o n s are e q u i l i b r i u m  values measured on a B e n d i x - E r i c s o n ETL-NPL Automatic P o l a r i m e t e r (Type 143A) are  uncorrected.  a t 21- - 2 ° .  Melting points  quoted  Chromatograms were run by the descending  technique i n the f o l l o w i n g s o l v e n t s : (A) e t h y l a c e t a t e a c e t i c a c i d - formic a c i d - water ethanol - water water  (18:7:8).  (18:3:1:4);  (B) 1-butanol -  (4:l:5)j  (C) e t h y l acetate - a c e t i c a c i d -  Silica  g e l t h i n l a y e r p l a t e s were run by the  ascending technique i n the f o l l o w i n g s o l v e n t s : (D) e t h y l ether - toluene ( 2 : l ) j (F)  (E) benzene - methanol  butanone - water azeotrope;  e t h y l ether - water  (9:6:3:1).  (19:l)j  (G) 1-butanol - a c e t i c a c i d Sugars were d e t e c t e d on  paper chromatograms by the p - a n i s i d i n e - t r i c h l o r o a c e t a t e (123) f o r r e d u c i n g sugars and periodate-permanganate (124) f o r non-reducing sugars. l a y e r p l a t e s was  spray  spray  D e t e c t i o n of sugars on t h i n  accomplished by s p r a y i n g with c o n c e n t r a t e d  s u l p h u r i c a c i d and h e a t i n g the p l a t e at 150°. Benzyl H e p t a - O - a c e t y l - p -maltoside To acetobromomaltose  (16.6  g) prepared from maltose  by the method of B a r c z a i - M a r t o s and Korosy (86), was  (10 g)  added  f r e s h l y d i s t i l l e d b e n z y l a l c o h o l (32 ml) and mercuric cyanide (6  g).  The mixture was heated to 85° on a water bath and  -55-  stirred was  v i g o r o u s l y f o r 45 minutes.  poured  with s t i r r i n g  5° f o r 3 hours.  solution  i n t o ethanol (90 ml) and c o o l e d to  The crude product  acetobrom sugar) was  The r e s u l t i n g  (10.5  g, 61% based on the  c o l l e c t e d by s u c t i o n f i l t r a t i o n .  R e c r y s t a l l i z a t i o n from e t h a n o l y i e l d e d m a t e r i a l m e l t i n g a t 124-125!  L i t . (88), m.p.  125°.  Benzyl j3 - M a l t o s i d e D e a c e t y l a t i o n of b e n z y l h e p t a - O - a c e t y l - ^ - m a l t o s i d e  was  accomplished with methanol s a t u r a t e d with ammonia as d e s c r i b e d by F i s c h e r and Kogl (88).  R e c r y s t a l l i z a t i o n from methanol -  e t h y l a c e t a t e gave the c r y s t a l l i n e g l y c o s i d e , m.p. Lit.  (87), m.p.  148-149°.  147-148.°  Platinum Oxidation C a t a l y s t M o d i f i c a t i o n of a method of Brown (125) f a c i l i t a t e d p r e p a r a t i o n of an a c t i v e platinum c a t a l y s t .  To carbon  the  (10 g,  Darco G-60), d i g e s t e d o v e r n i g h t i n 6N h y d r o c h l o r i c a c i d , washed f r e e of c h l o r i d e with d i s t i l l e d water and d r i e d a t for  f o u r hours, a s o l u t i o n of c h l o r o p l a t i n i c a c i d  5 0 % aqueous e t h a n o l (50 ml) was s o l u t i o n of sodium borohydride added s l o w l y with s t i r r i n g . acid  (10 ml) was  added.  (5 g) i n  To t h i s mixture, a  (2.5 g) i n e t h a n o l (100 ml)  was  A f t e r 5 minutes 6N h y d r o c h l o r i c  added and the suspension s u c t i o n  The p r e c i p i t a t e was  120°  filtered.  washed f r e e of c h l o r i d e with d i s t i l l e d  -56-  water and d r i e d i n vacuum over phosphorus pentoxide. product  (12 g) was  d r y i n g was  p y r o p h o r i c and i n l a t e r  The  experiments  not c a r r i e d out and the product was  kept as a  moist p a s t e . C a t a l y t i c O x i d a t i o n of B e n z y l To a s o l u t i o n of b e n z y l  |4-Maltoside ^ - m a l t o s i d e (5 g) and  b i c a r b o n a t e (1 g) i n d i s t i l l e d water (100 ml) was platinum c a t a l y s t  (5 g ) .  sodium  added  The mixture was maintained a t 65°  and m a g n e t i c a l l y s t i r r e d f o r 6 hours during which time a stream of oxygen was gas d i s p e r s i o n tube.  passed i n t o the s o l u t i o n through a A f t e r c o o l i n g the mixture was  through C e l i t e , a c i d i f i e d with Amberlite IR 120 s l o w l y through a column of D u o l i t e A-4 r e s i n was  (0H~).  filtered  (H ) and  passed  The D u o l i t e  washed with water (500 ml) and the combined e l u a t e s  evaporated to r e c o v e r unreacted b e n z y l The D u o l i t e r e s i n was  ^ - m a l t o s i d e (3-4 g ) .  e l u t e d with N NaOH (15 m l ) , washed  with water (100 ml) and the combined e l u a t e a c i d i f i e d passage through Amberlite IR-120 ( H ) . V  obtained was  The a c i d  by  mixture  evaporated to a brown s i r u p ( l g ) .  Methyl(Benzyl Hepta-O-acetyl- ^°maltosid)uronate I To the a c i d mixture  (1.5 g) d i s s o l v e d i n methanol (15  excess diazomethane i n ether was the excess diazomethane was  added.  ml)  A f t e r ten minutes  decomposed with g l a c i a l a c e t i c  acid,  and the s o l u t i o n evaporated  to a s i r u p .  This m a t e r i a l was  a c e t y l a t e d i n p y r i d i n e (20 ml) with a c e t i c anhydride overnight.  Recovery i n the normal way y i e l d e d a s i r u p which  crystallized.  R e c r y s t a l l i z a t i o n from ethanol or methanol  y i e l d e d the methyl e s t e r hexaacetate 2.04 i n CHC1 ). 3  C, 55.95j  H, 5.62#.  Barium (Benzyl  (0.8 g) m.p. 164-165°,  Calculated f o r 3„ 4o°l8 c  Found: C, 53.80;  H  !  H, 5.71#.  ^-Maltosid)uronate  To a s o l u t i o n of the methyl e s t e r hexaacetate i n methanol (20 ml) a s a t u r a t e d aqueous barium solution  (50 ml)  (415 mg)  hydroxide  (40 ml) was added and the s o l u t i o n r e f l u x e d on a  steam bath f o r 90 minutes.  The s o l u t i o n was n e u t r a l i z e d  with carbon d i o x i d e , f i l t e r e d , and the p r e c i p i t a t e washed with water (15 ml).  The combined f i l t r a t e s were a c i d i f i e d by  passage through Amberlite glassy s o l i d .  IR-120 ( H ) and evaporated +  to a  The s o l i d was d i s s o l v e d i n water (2 ml) and  n e u t r a l i z e d with s a t u r a t e d aqueous barium hydroxide.  The  p r e c i p i t a t e obtained upon the a d d i t i o n of ethanol (30 ml) was c e n t r i f u g e d , washed with ethanol (10 ml) and was d r i e d by s o l v e n t exchange with ether to give a white powder (300 mg) 1.53 i n H 0 ) . g  -58-  Maltobiouronic Acid A small s c a l e experiment (8.25 mg  of barium s a l t )  conducted i n a Warburg type microhydrogenator. was  was  Hydrogenolysis  complete a f t e r two hours with the hydrogen uptake constant  at 1.04  moles.  To a s o l u t i o n of the barium s a l t (202 mg)  i n water  (10 ml)  was added p a l l a d i u m oxide on barium sulphate c a t a l y s t (270  mg).  The mixture was hydrogenolyzed a t room temperature i n a Paar apparatus at a pressure of one atmosphere. the  mixture was  A f t e r two hours  f i l t e r e d , the p r e c i p i t a t e washed with water  (10 ml) and the combined  f i l t r a t e s a c i d i f i e d by passage  through Amberlite IR-120 ( H ) and evaporated to a s i r u p (138 +  mg).  F r e e z e - d r y i n g y i e l d e d a product which analyzed as a monohydrate. A f t e r d r y i n g overnight i_n vacuo  (0.02 mm)  a t 80° the product  had l o s t a weight e q u i v a l e n t to 1.2 moles of water.  Upon  d r y i n g a t 100° f o r 36 hours a f u r t h e r 0.5 moles of water was l o s t .  Drying was  d i s c o n t i n u e d at t h i s stage as the a c i d  began to darken i n d i c a t i n g decomposition. equivalent: calculated for ig 2g°_3 c  D  found 367, L ^ J C  12 22°13 H  H, 5.76$. ' system A.  (  m  o  n  o  h  y  d  1  r  1  a  t  6  e  ° )  2  J  c  »  (  H  ,  5  2  i n  38.50;  H  m o n o n  2 )« 0  Neutralization y d r a t e ) , 374;  Calculated for  H, 5.88$.  Found: C, 38.26;  R 0.051, R 0.33, R 0.90, —± —glucose ' —maltose f  9  solvent  -59-  Methyl  (Hepta-O-acetyl- j2 - m a l t o s i d j u r o n a t e  To m a l t o b i o u r o n i c a c i d  (55 mg)  i n methanol (5 ml)  was  added excess diazomethane i n e t h e r , and a f t e r 10 minutes the s o l u t i o n was  evaporated  to dryness.  A c e t i c anhydride  and anhydrous sodium acetate (0.5 g) were added and mixture was  heated on a steam bath f o r two hours.  poured  C r y s t a l s (50 mg)  the mixture  were obtained which  upon r e c r y s t a l l i z a t i o n from methanol melted D  ml)  i n t o i c e water and e x t r a c t e d i n t o c h l o r o f o r m i n  the u s u a l manner.  [o£\  The  (10  77° ( c , 0.54  i n CHC1 ).  a t 197-198°.  Calculated for C g H  3  7  3 6  0  1 9  J  C, 48.80} H, 5.42$. Found: C, 4 9 . 2 9 j H, 5.53$. Hydrogenolysis of methyl ( b e n z y l - h e x a - O - a c e t y l - p - m a l t o s i d ) uronate catalyst  (145 mg) (75 mg)  i n glacial acetic acid  (5 ml) with  f o r 10 hours a t atmospheric  Pd/C  pressure gave  a m a t e r i a l which upon a c e t y l a t i o n as d e s c r i b e d above gave methyl ( h e p t a - O - a c e t y l - p - m a l t o s i d ) u r o n a t e  (43 mg).  Melting  p o i n t and mixed m e l t i n g p o i n t 197-198 o . C o n s t i t u t i o n of M a l t o b i o u r o n i c A c i d To m a l t o b i o u r o n i c a c i d borohydride  (30 mg)  room temperature  added.  to dryness.  i n methanol ( 3 x 5  i n water (5 ml)  After  the s o l u t i o n was  a c i d and evaporated with 3$ HC1  was  (6 mg)  seventeen  hours a t  n e u t r a l i z e d with The  s i r u p was  sodium  acetic  evaporated  ml) and the r e s i d u e d i s s o l v e d  -60-  i n water (5 ml), passed through Amberlite IR-120 (H ) +  evaporated to dryness. in N H S0  The r e s u l t i n g m a t e r i a l was  and  dissolved  4  (3 ml) and h y d r o l y z e d at 100° i n a s e a l e d tube  overnight.  N e u t r a l i z a t i o n of the h y d r o l y z a t e with washed  2  barium  carbonate  gave a f i l t r a t e  which upon a c i d i f i c a t i o n  p a s s i n g through Amberlite IR-120 (H ) +  a c i d and  s o r b i t o l upon paper  indicated only glucuronic  chromatography.  Reaction of Benzyl H e p t a - O - a c e t y l - ^ - m a l t o s i d e  To a suspension of L i A l H (5 ml) was  4  with L i A l H ^  (0.2 g) i n dry t e t r a h y d r o f u r a n  added a s o l u t i o n of b e n z y l hepta-O-acetyl-(?> -  m a l t o s i d e (54 mg) i n t e t r a h y d r o f u r a n (5 ml).  The mixture  s t i r r e d under r e f l u x f o r 1 hour, a f t e r which time LiAlH  4  by  was  destroyed with e t h y l a c e t a t e .  was  excess  The mixture  was  then n e u t r a l i z e d with g l a c i a l a c e t i c a c i d and evaporated to dryness.  To the r e s i d u e anhydrous sodium acetate (0.2  and a c e t i c anhydride at  room temperature  (5 ml) were added and the mixture overnight.  g) left  The a c e t y l a t i o n mixture  was  poured i n t o i c e water (50 m l ) , e x t r a c t e d with c h l o r o f o r m (3 x 20 m l ) , e x t r a c t s washed i n the u s u a l way e x t r a c t evaporated to a s i r u p .  The  and the d r i e d  s i r u p upon s i l i c a g e l  t h i n l a y e r chromatography ( s o l v e n t E) i n d i c a t e d two components.  The f a s t e r of the two  corresponded  m a t e r i a l , benzyl hepta-O-acetyl-^ -maltoside. was  more i n t e n s e and was  major  to the The  presumably nona-O-acetyl  starting  second  spot  maltitol.  -61-  1,6-Anhydro-^3 -maltose To a suspension of h e x a - 0 - a c e t y l ~ l , 6 - a n h y d r o - ^ - m a l t o s e (41) (7 g) i n methanol (95 ml) was added a s o l u t i o n of sodium methoxide i n methanol (5 ml).  0.1M  A f t e r 4 hours the  a c e t a t e had d i s s o l v e d , and a f t e r a f u r t h e r 14 hours the s o l u t i o n was n e u t r a l i z e d with IR 120 ( H ) . f  The s o l u t i o n  f i l t e r e d and evaporated to give a s i r u p which was i n r e f l u x i n g methanol (50 m l ) . with e t h y l a c e t a t e  M.p.  156-158°. [_o£~\  m.p.  150°.  H, 6.17$.  D  The hot s o l u t i o n was  7  _ 108° ( c , 7.3 i n H 0 ) . 2  9  thinned  The c r y s t a l s  and r e c r y s t a l l i z e d i n the same manner.  °'  C  a  l  Found: C, 44.02;  Direct Tosylation  dissolved  (100 ml) and allowed to c o o l .  (5.2 g) were f i l t e r e d  was  c  u  l  a  t  e  d  f  o  r  C  L i t . (40),  12 20°10 H  :  G  »  4 4  *  4 4  5  H, 5.93$.  of 1,6-Anhydro-^-maltose  To 1,6-anhydro-^-maltose (1 ml) was added t o s y l c h l o r i d e The s o l u t i o n was l e f t  (100 mg) d i s s o l v e d i n p y r i d i n e (53 mg) i n p y r i d i n e  ( l ml).  17 hours at 5°, a f t e r which time t h i n  l a y e r chromatography ( s o l v e n t F) i n d i c a t e d three monotosylates and two d i t o s y l a t e s i n a d d i t i o n to s t a r t i n g m a t e r i a l . the  Varying  temperature of the r e a c t i o n and c o n c e n t r a t i o n of the  reagents d i d not seem to change the r e l a t i v e amounts of the products as i n d i c a t e d by t h i n l a y e r chromatography.  Direct  a c e t y l a t i o n of the t o s y l a t i o n mixture i n d i c a t e d o n l y two t o s y l a t e d products on t h i n l a y e r chromatography i n solvent  D,  -62-  presumably to  due to the i n a b i l i t y of the chromatographic  separate i n d i v i d u a l isomers.  by s p r a y i n g with diphenylamine ultraviolet radiation  system  Tosyl e s t e r s were i d e n t i f i e d i n e t h a n o l and viewing under  (126).  l,6-Anhydro-6'-O-trityl-^-maltose To 1,6-anhydro-^3-maltose (2.2 g) powdered and over PgOg i£ vacuo f r e s h l y d i s t i l l e d p y r i d i n e added. to  dried  (25 ml)  was  The mixture was warmed to e f f e c t s o l u t i o n and c o o l e d  room temperature.  1.5 mole equiv.) was temperature  Recrystallized t r i t y l  dropwise to i c e water  The p y r i d i n e s o l u t i o n was  (500 ml) with continuous  g.,  added  stirring.  then e x t r a c t e d with c h l o r o f o r m (2 x 100 ml),  and the c h l o r o f o r m e x t r a c t s were amalgamated and through C e l i t e .  (2.85  added and the s o l u t i o n l e f t at room  f o r 5 hours.  The mixture was  chloride  The c l e a r s o l u t i o n was  filtered  thinned w i t h an equal  volume of petroleum ether (30-60°) and the p r e c i p i t a t e c o l l e c t e d (1.9 g).  The t r i t y l ether was r e c r y s t a l l i z e d three  times from ethanol-water (1*2, 75 ml/g) to y i e l d m a t e r i a l J  m e l t i n g a t 141-142°.  D  40.8° ( c , 2.53  i n MeOH).  C a l c u l a t e d f o r monohydrate C3iH3 Oio*HgO: C, 63.70j 4  Found: C, 63.78j  H, 6.16$.  H, 6.26$.  Penta-0-acetyl-l,6-anhydro-6'-O-trityl-^-maltose To l , 6 - a n h y d r o - 6 - O - t r i t y l - ^ 3 - m a l t o s e 1  (1.5 g) d i s s o l v e d  -63-  in pyridine  (15 ml) was  added and  the s o l u t i o n l e f t o v e r n i g h t at room temperature.  Dropwise  addition  (15 ml) a c e t i c anhydride  of the a c e t y l a t i o n  gave the a c e t y l a t e d  s o l u t i o n i n t o i c e water (1 L)  ether (2.2 g ) .  e t h a n o l - water (3:1, 30 ml/g) ^c^J  101-102°. for  C  4i 44°i5 H  :  c  D >  S 5  gave m a t e r i a l  « ° ° (c> 1-55  63.40j  H,  Recrystallization  i n CHClg).  5.67$.  from  m e l t i n g at Calculated  Found: C, 62.98j  H,  5.84$. 2,2',3,5',4'-Penta-0-acetyl-l,6-anhydro-^ff -maltose Penta-0-acetyl-l,6-anhydro-6 »-0-trityl-^_t-maltose was  dissolved  solution  was  i n 80$ aqueous a c e t i c a c i d kept 3 hours a t 50°.  water (90 ml) was hours.  (40 ml) and  added and the mixture kept at 5° f o r 18  The mixture  was  filtered,  the p r e c i p i t a t e washed with  (10 m l ) , and the combined  evaporated  Crystals  to a s i r u p .  (665 mg)  d i s s o l v i n g the s i r u p i n hot 2-propanol from the same s o l v e n t  C  j^o-J  22 30°15 H  :  C  »  4  9  Penta-0-acetyl-l  (40 ml/g)  43.4° ( c , 2.43  D  «  4  4  J  H  »  5.62$.  filtrates  were obtained by  (25 ml).  Recrystallization  gave c r y s t a l s m e l t i n g a t i n CHC1 ). 3  Calculated  Found: C, 49.87;  for  H, 5.70$.  ,6-anhydro-6 ' -0-tosyl-y£?-maltose  To the pentaacetate tosyl chloride  the  To the warm s o l u t i o n ,  25$ aqueous a c e t i c a c i d  82-83°.  ( l g)  (4 g) d i s s o l v e d  (7.5 g) was  added.  After  i n dry pyridine 5 hours a t room  (18  ml)  -64-  temperature,  3 drops of water were added to hydrolyze excess  t o s y l c h l o r i d e and the s o l u t i o n was (80 m l ) .  This mixture was  poured  i n t o i c e water  e x t r a c t e d with c h l o r o f o r m (3 x 100 m l ) ,  and the c h l o r o f o r m e x t r a c t s were combined and washed with water (7 x 100 ml). chloride, f i l t e r e d  The  s o l u t i o n was  and evaporated to give a s i r u p which,  when d i s s o l v e d i n hot 2-propanol crystalline tosylate  (4.25  same s o l v e n t (36 ml/g) 1.00 H , 5.23j  C, 50.58;  d r i e d with calcium  S,  g).  (155 m l ) , gave the R e c r y s t a l l i z a t i o n from  gave m a t e r i a l m e l t i n g a t i n CHC1 ). 3  4.65$.  the  170-171°.  Calculated for  c  j?9  H,  Found: C, 50.48;  H  °i7 * S  5 6  5.11j  S, 4.36$. Penta-0-acetyl-l,6-anhydro-6'-azido-6 -deoxy-p-maltose 1  P e n t a - O - a c e t y l - l , 6 - a n h y d r o - 6 ' - 0 - t o s y l - p -maltose d i s s o l v e d i n N, N-dimethylformamide (75 ml) was  (1.5  heated  a steam bath with sodium azide (1.5 g) f o r one hour and stirred frequently.  A f t e r c o o l i n g , the s o l u t i o n was  g)  on was  poured  i n t o an equal volume of water and the mixture e x t r a c t e d with c h l o r o f o r m (4 x 100 ml). e x t r a c t was  The combined c h l o r o f o r m  thoroughly washed with water (8 x 200 m l ) , d r i e d  over c a l c i u m c h l o r i d e , f i l t e r e d , and evaporated to a s i r u p . The  s i r u p was  d i s s o l v e d i n hot 2-propanol  c o o l e d to give c r y s t a l s lization  (1.06  and the  g) of the 6'-azide.  from the same s o l v e n t (50 ml/g)  yielded  solution Recrystalcrystals  -65-  m e l t i n g at 151-152°.  47.9° ( c , 2.55  \j>C^\  C a l c u l a t e d f o r C g H g 0 N 3 : C, 47.23j 2  9  Found: C, 47.68;  H,  14  H, 5.49;  i n CHClg).  5.19;  N, 7.51$.  N, 7.58$.  6'-Amino-6'-deoxy-maltose To a s o l u t i o n of deoxy- ^-maltose 0.1  penta-0-acetyl-l,6-anhydro-6•-azido-6 1  (560 mg)  i n methanol (20 ml) was  M sodium methoxide i n methanol (4 ml).  at room temperature, IR 120  (H ) +  the s o l u t i o n was  and evaporated  A f t e r 18 hours  n e u t r a l i z e d with  to a s i r u p which p l a i n l y showed  an i n f r a r e d a b s o r p t i o n band near 2100 of the azide group (127).  The  ora"^ c h a r a c t e r i s t i c  s i r u p was  dissolved i n ethanol  (15 ml) and 10$ p a l l a d i u m on c h a r c o a l (300 mg) The mixture  was  maintained  while a f i n e stream solution.  was  of hydrogen was  bubbled  through  continued f o r a f u r t h e r 2 hours.  removed by f i l t r a t i o n  the The  catalyst  and the s o l u t i o n evaporated  a c h r o m a t o g r a p h i c a l l y pure s i r u p R^ with n i n h y d r i n .  the  made s l i g h t l y  a c i d i c with 3$ hydrogen c h l o r i d e i n methanol and  was  added.  at 65° by means of a water bath  A f t e r 45 minutes the s o l u t i o n was  hydrogenation  added  T h i s m a t e r i a l was  to  give  0.054, s o l v e n t B, d e t e c t e d d i s s o l v e d i n 0.15N  hydrochloric o  a c i d and heated i n a s e a l e d tube h y d r o l y s a t e was  f o r 13 hours at 100  n e u t r a l i z e d with s i l v e r carbonate,  and a d j u s t e d t o pH  5 with 0.3N  s o l v e n t B i n d i c a t e d o n l y two  HC1.  .  The  filtered  Chromatography i n  ninhydrin positive materials  -66  Rf 0.041  and  0.054.  However p - a n i s i d i n e - t r i c h l o r o a c e t a t e  spray i n d i c a t e d glucose,  the m a t e r i a l  showing R  slower running degradation products. was  The  C, and  solvent  G.  a l s o by  t h i n l a y e r chromatography (128)  Preparative  0.041  material.  of  6'-araino-6•-deoxy-maltose.  The  f  0.041  co-workers  very low  y i e l d prevented  1 2  3.97$.  Potassium  Thiolacetate  2 3  0  To a s o l u t i o n of potassium carbonate (36  evaporated to dryness and  e x t r a c t e d with ethanol f i l t e r e d and  (2 x 250  the r e s i d u e The  evaporated to dryness.  d i s s o l v e d i n hot absolute carbon (1 g) was  ml).  ethanol  added, the  3.70$.  g) i n water  added r e d i s t i l l e d t h i o l a c e t i c a c i d (22 ml).  s o l u t i o n was  any  D  C a l c u l a t e d f o r C H 0 _ N » H C 1 : N,  Found: N,  was  material  material i s  attempts to prepare s u i t a b l e d e r i v a t i v e s . i n HgO).  3MM  6-amino-6-deoxy-glucose, i d e n t i c a l  This i n d i c a t e s that the R  ( c , 0.3  in  the  of a sample of t h i s  to m a t e r i a l prepared by the method of Cramer and (96).  systems  paper chromatography on Whatman  Hydrolysis  i n d i c a t e d glucose and  was  and  presence of glucose  paper i n s o l v e n t B gave a small amount (10 mg)  ml)  0.041  i n d i c a t e d by comparison with standards i n s o l v e n t  A, B,  R^  f  (500  The was  combined e x t r a c t The  (150 ml),  residue  was  decolourizing  s o l u t i o n f i l t e r e d and  allowed to  -6 7off cool.  A f t e r 4 hours a t 5°, the s a l t was  over c a l c i u m c h l o r i d e .  T i e l d 14.6  filtered/and dried  g (129).  P e n t a - O - a c e t y l - 6 - S - a c e t y l - l , 6 - a n h y d r o - 6 ' - d e o x y - ^ -maltose 1  To a s o l u t i o n of p e n t a - 0 - a c e t y l - l , 6 - a n h y d r o - 6 - O - t o s y l 1  ^-maltose  (500 mg)  i n N,N-dimethylformamide (5 ml)  added potassium t h i o l a c e t a t e  (220 mg).  The mixture  heated on a steam bath f o r h a l f an hour. water (50 ml) was chloroform was  After  added and the mixture e x t r a c t e d  (4 x 50 ml).  The  was was  cooling, with  combined chloroform s o l u t i o n  t h o r o u g h l y washed with water (7 x 100 m l ) , d r i e d  over  calcium c h l o r i d e , f i l t e r e d and evaporated to a s i r u p . s i r u p was cooling lization  dissolved  i n hot 2-propanol  gave c r y s t a l s (300 mg) of t h i s m a t e r i a l  Calculated  Found; C, 48.74;  H,  of the S-acetate.  from 2-propanol  c r y s t a l s m e l t i n g a t 219-220°. CHGlg).  (45 ml) which  \^oC~\  for C^H^O^-Si 5.57;  D  upon  Recrystal-  (80 ml/g)  yielded  34.6° (c_, 0.72  C, 48.66j H,  The  in  5.41j  S, 5.41$.  S, 5.24$.  H e p t a - O - a c e t y l - 6 ' - S - a c e t y l - 6 - d e o x y - Q^-maltose 1  Penta-O-acetyl-6'-S-acetyl-l,6-anhydro-6 -deoxy-^-maltose 1  (150 mg)  was  dissolved  i n the a c e t o l y s i s mixture  (HgS0 :Ac20:AcOH = 1:70:30). 4  the s o l u t i o n was  After  added dropwise  white powder so o b t a i n e d was  (3 ml)  3 hours a t room  temperature  to i c e water (25 ml).  f i l t e r e d and a p o r t i o n  The  recrystallized  -6 8  from ethanol-water (1:5, 100 ml/g).  Further  recrystallization  d i d not remove a small amount of the /& -anomer which was apparent on t h i n l a y e r chromatography i n s o l v e n t D. 115° (c, 0.79 i n C H C l j ) .  D  C  28 58°18 H  S :  C  »  4 8  '  4 2  ?  H  »  5.49$.  M.p.  Calculated f o r  Found: C, 48.67j  H, 5.79$.  6'-Deoxy-6'-mercapto-maltose To hepta-O-acetyl-6'-S-acetyl-6'-deoxy-0(-maltose (120 i n methanol (4 ml) was added a s o l u t i o n of 0.1M methanol (1 m l ) .  mg)  sodium methoxide  A f t e r the s o l u t i o n had been kept at room  temperature o v e r n i g h t , i t was n e u t r a l i z e d with IR 120 (H*), f i l t e r e d and evaporated to a s i r u p . showed two products R^ 0.018  Chromatography i n s o l v e n t A  and 0.25 which were the d i s u l p h i d e  and the f r e e t h i o l r e s p e c t i v e l y .  When excess 2-mercapto-ethanol  and 1 drop of concentrated ammonia were added, only the more mobile compound was p r e s e n t .  Chromatography of the a c i d  h y d r o l y s a t e of 6'-deoxy-6 -mercapto-maltose 1  and 6-deoxy-6-mercapto-glucose.  i n d i c a t e d glucose  The l a t t e r was prepared by  a route s i m i l a r to t h a t employed by Akagi, Tejima and Haga (150). Borohydride r e d u c t i o n f o l l o w e d by h y d r o l y s i s s o r b i t o l and 6-deoxy-6-mercapto-glucose. crystallize  indicated  Attempts to  the c h r o m a t o g r a p h i c a l l y pure d i s a c c h a r i d e were  unsuccessful.  I n s u f f i c i e n t m a t e r i a l was recovered to obtain  suitable analyses.  D  1 5 7  » ° 6  (£>  2  *  0 2  i n  H  p ^* 0  -69-  Penta-0-acetyl-l,6-anhydro-6 -deoxy-6 ' -iodo-^p -maltose 1  To a s o l u t i o n of the 6'-O-tosylate (1.2 g) i n dimethylformamide iodide  (4 g ) .  1_- hours. water  (50 ml) was  added f i n e l y powdered  sodium  The s o l u t i o n was heated on a steam bath f o r  A f t e r c o o l i n g , the s o l u t i o n was  d i l u t e d with  (100 m l ) , and e x t r a c t e d w i t h c h l o r o f o r m (4 x 50 ml).  The combined chloroform e x t r a c t was  washed with water  100 m l ) , d r i e d over calcium c h l o r i d e , f i l t e r e d The s i r u p obtained was from which c r y s t a l s  (1.04  Calculated f o r C^H  Found; C, 41.09;  (100  ml)  g) were obtained on c o o l i n g .  m a t e r i a l m e l t i n g at 194-195°. _J>^ CHC1 ).  (6 x  and evaporated.  d i s s o l v e d i n hot 2-propanol  R e c r y s t a l l i z a t i o n from the same solvent  5  N,N-  3  O Ii u  42 D  (100 ml/g)  «° 0  1  C, 40.99j  «  gave 05  i n  H, 4.50$.  H, 4.58$.  Penta-0-acetyl-l,6-anhydro-6'-deoxy- j$ -maltose To a s o l u t i o n c o n t a i n i n g  penta-O-acetyl-1,6-anhydro-6'-  deoxy-6*-iodo-^S-maltose (0.5 g) and p y r i d i n e ethanol (10 ml) was The mixture was  added 10$ p a l l a d i u m on c h a r c o a l (0.5 g). o  kept at 60  stream of hydrogen  was  b y means of a water bath and a  i n t r o d u c e d through a c a p i l l a r y .  A f t e r f o u r hours the c a t a l y s t was f i l t e r e d evaporated.  The r e s u l t i n g s i r u p was  (30 ml) washed with 1$ sodium washed with water  (0.1 ml) i n  (4 x 30 ml).  and the  solution  dissolved i n chloroform  thiosulphate  (15 ml) and  The c h l o r o f o r m s o l u t i o n  finally was  -70-  d r i e d over c a l c i u m c h l o r i d e and evaporated to give a f a i n t l y yellow s i r u p .  The s i r u p was  (25 ml) which upon c o o l i n g (252 mg).  dissolved  gave the c r y s t a l l i n e  deoxy sugar  R e c r y s t a l l i z a t i o n from 2-propanol (40 ml/g)  material  m e l t i n g a t 141-142 . [ j ^ l  CHC1 ).  Calculated  3  i n hot 2-propanol  Found: C, 50.87;  for 0  H,  2 2  H  3 0  0  1 4  :  D 4«5° 4  C, 50.96J  gave  ( c , 0.88 i n H, 5.77$.  5.89$.  6 -Deoxy-maltose 1  Penta-0-acetyl-l,6-anhydro-6'-deoxy- p - m a l t o s e (485 was  dissolved  i n the a c e t o l y s i s mixture (10 ml)  (5 min) to 138.8°  The f l a s k was added.  (H S0 :AcgO: 2  4  The o p t i c a l r o t a t i o n v a r i e d from £ j ^ J  AcOH = 1:70:30). 89.2°  mg)  (2 h) a f t e r which time i t was c o n s t a n t .  c o o l e d i n i c e a f t e r 3 hours and i c e (5 g)  The s u l p h u r i c  a c i d was  was  n e u t r a l i z e d by the a d d i t i o n  M barium a c e t a t e and the p r e c i p i t a t e removed by The s o l u t i o n was  D  of  centrifugation.  evaporated to give a s i r u p which was evaporated  to dryness with e t h a n o l (3 x 10 ml).  The hepta-O-acetate  c o u l d be o b t a i n e d as an amorphous powder on p r e c i p i t a t i o n from alcohol-water.  dissolved  i n methanol  (10 ml) and a s o l u t i o n of 0.1 M sodium methoxide  i n methanol  (2 ml) was  The s i r u p y acetate was  added.  s o l u t i o n was  A f t e r 17 hours a t room temperature the  n e u t r a l i z e d with IR 120  evaporated to a s i r u p .  (H*), f i l t e r e d  and  The s i r u p , which was c h r o m a t o g r a p h i c a l l y  pure, c o u l d not be induced to c r y s t a l l i z e even a f t e r  chromatography  -71-  on Dowex 50 ¥ x 2 ( L i  v  s a l t ) (131).  of the sugar with 2 N s u l p h u r i c material  H y d r o l y s i s of a sample  a c i d i n d i c a t e d glucose and  i d e n t i c a l to 6-deoxy-glucose  of F i s c h e r  and Zach  (132).  prepared by the procedure  A second sample, which had been  reduced with sodium borohydride b e f o r e h y d r o l y s i s ,  A portion in pyridine  of the 6'-deoxy-maltose (23.3 mg)  i n t o i c e water  water  was  (1 ml) and a c e t i c anhydride (4 ml) was  The s o l u t i o n was  30 m l ) .  indicated  left  dissolved  added.  30 hours a t room temperature,  poured  (40 m l ) , and e x t r a c t e d with c h l o r o f o r m (3 x  The combined e x t r a c t was  washed t h o r o u g h l y with  (6 x 50 m l ) , d r i e d over c a l c i u m c h l o r i d e , f i l t e r e d  evaporated.  The r e s u l t i n g s i r u p was  d i s s o l v e d i n hot ethanol  (2 ml) and the s o l u t i o n , upon c o o l i n g , y i e l d e d hepta-0-acetyl-6 '-deoxy-  a  64 (£, 0.68 H, 5.80$.  i n CHC1 ). 3  B  -maltose.  Calculated  Found: C, 49.57;  and  M.p.  183-185°.  for 26 36°17 C  crystalline  H  :  C  »  ("(^"1 5 0  »  3 2  n  J  H, 5.55$,  C a t a l y z e d Lead T e t r a a c e t a t e O x i d a t i o n s Methyl  o^-D-Glucopyranoside  To a s o l u t i o n of methyl  ^-D-glucopyranoside  (26.4  mg.,  -72-  1.36 x 10""* moles) i n g l a c i a l a c e t i c a c i d  (5 ml) was added  50$ aqueous potassium a c e t a t e (0.2 ml) and 0.0622 M l e a d tetraacetate i n g l a c i a l acetic acid. consumption  Lead  tetraacetate  was estimated by i o d i m e t r y as o u t l i n e d by P e r l i n  (104).  1,6-Anhydro- ji -D-glucose 1,6-Anhydro- j§-D-glucose m.p. 174°, l i t .  (133), m.p.  172°, (19.0 mg., 1.17 x 1 0 ~ moles) was o x i d i z e d u s i n g the 4  same q u a n t i t i e s as f o r methyl  ^-D-glucopyranoside.  Table 1 Time  Methyl  (min)  o(-D-glucopyranoside  1,6-Anhydro-^-D-glucose  moles of t e t r a a c e t a t e consumed per mole of sugar  30  0.07  0.03  120  0.34  0.33  300  0.66  0.75  420  0.91  1.04  1500  2.02  2.12  Benzyl 4 ' , 6 - 0 - B e n z y l i d e n e - 6 - 0 - t o s y l - ^ - m a l t o s i d e t  To a s o l u t i o n of b e n z y l 4 , 6 - O - b e n z y l i d e n e - ^ - m a l t o s i d e 1  (650 mg) (134) i n d r y p y r i d i n e tosyl chloride  1  (5 ml) was added r e c r y s t a l l i z e d  (286 mg) i n d r y p y r i d i n e  (5 ml).  The r e a c t i o n  proceeded 40 hours, d u r i n g which time samples were removed f o r  73-  t h i n l a y e r chromatography ( s o l v e n t indicated  that  F).  Chromatography  three major products were formed.  the products t r a v e l l e d a t a r a t e  Two  corresponding to mono-  t o s y l a t e s , the other corresponding to a d i t o s y l a t e . obvious that specific  the s e l e c t i v i t y of t o s y l a t i o n was  to o b t a i n the 6 - t o s y l  of  not  I t was sufficiently  derivative.  B e n z y l 4 ' , 6 ' - O - B e n z y l i d e n e - 6 - 0 - t r i t y l - y f f -maltoside To a s o l u t i o n of b e n z y l 4 ' ,6 ' - O - b e n z y l i d e n e - ^ - m a l t o s i d e (35 mg)  i n dry p y r i d i n e  (25 mg).  The r e a c t i o n  i n solvent  (0.35 ml) was was  added t r i t y l  f o l l o w e d by t h i n l a y e r  D, which i n d i c a t e d no r e a c t i o n  a f t e r 3 days a t room  chloride chromatography  had o c c u r r e d even  temperature.  Benzyl 4',6 -0-Benzylidene-6-0-mesyl-^ 1  -maltoside  To a s o l u t i o n of b e n z y l 4 ,6 ' - O - b e n z y l i d e n e - ^ - m a l t o s i d e 1  (300 mg)  i n dry c h l o r o f o r m (25 ml) was  and the s o l u t i o n c o o l e d to 5°. then added.  The  Mesyl c h l o r i d e  The s o l u t i o n remained  drop of water was s o l u t i o n was  added dry p y r i d i n e (0.06 ml)  (5 ml) was  at 5° f o r 5 hours, and a  then added to hydrolyze any excess reagent. e x t r a c t e d with water (6 x 30 m l ) , d r i e d  calcium c h l o r i d e , and evaporated.  over  C r y s t a l s which melted at  86-89° were o b t a i n e d from e t h y l acetate - petroleum ether (30-60°).  The c r y s t a l l i n e product was  shown by t h i n  layer  -74-  chromatography to be composed of about 70$ s t a r t i n g The minor component appeared c h r o m a t o g r a p h i c a l l y and was presumably the 6-0-mesyl  derivative.  material.  homogeneous  BIBLIOGRAPHY 1.  R. L. W h i s t l e r and B. Shasha.  2.  M. L. Wolfrom, M. I . Taha and D. Horton. 28, 3553 (1963).  3.  W. Koenigs and E. Knorr.  4.  W. L. Evans, D. D. Reynolds and E. A. Talley. Carbohydrate Chem. £ , 27 (1951).  5.  M. G. B l a i r  6.  R. W. B a i l e y and J . B. Pridham. Chem. 17, 121 (1962).  7.  S. B l a c k , G. G. S. Dutton and K. N. S l e s s o r . A Tabular L i s t of S y n t h e t i c D i s a c c h a r i d e s . Department of Chemistry, U n i v e r s i t y of B r i t i s h Columbia, Vancouver, B. C.  8.  R. U. Lemieux and B. F r a s e r - R e i d . (1964).  9.  P. A. J . Gorin and A. S. P e r l i n . (1961) .  and W. Pigman.  J . Org. Chem. 29, 880 (1964). J . Org. Chem.  Ber. 3 4 , 957 (1901). Advan.  Angew. Chem. £ 9 , 422 (1957). Advan. Carbohydrate  Can. J . Chem. 42, 532 Can. J . Chem. 39, 2474  10.  M. L. Wolfrom, A. 0. P i t t e t and I . C. G i l l a m . Acad. S c i . 47, 700 (1961).  Proc. N a t l .  11.  D. R. Lineback. (1962) .  University,  12.  H. Bredereck, A. Wagner, D. G e i s s e l and H. O t t . Chem. Ber. £ 5 , 3064 (1962).  13.  R. U. Lemieux and B. F r a s e r - R e i d . (1964).  14.  W. J . Hickinbottom.  15.  P. B r i g l .  16.  R. U. Lemieux.  17.  W. N. Haworth and W. J . Hickinbottom. 2847 (1951).  18.  R. U. Lemieux.  Ph.D. T h e s i s .  The Ohio State  Can. J . Chem. 42, 539  J . Chem. Soc. 3140 (1928).  Z. physioO. Chem. 122, 245 (1922). Advan. Carbohydrate Chem. 9, 1 (1954). J . Chem. Soc.  Can. J . Chem. 51, 949 (1955).  -76-  19.  R. U. Lemieux and G. Huber. (1953).  J . Am. Chem. Soc. 75, 4118 —  20.  A. P i c t e t and H. Vogel.  21.  A. P i c t e t .  22.  S. Haq and W. J . Whelan.  23.  E. Pacsu.  24.  B. L i n d b e r g .  25.  R. U. Lemieux, G. Huber and W. P. Shyluk. 33, 148 (1955).  26.  B. L i n d b e r g .  27.  I . Karasawa and R. O n i s h i . £ 5 , 813 (1961).  28.  I . J . G o l d s t e i n and W. J . Whelan. (1963).  29.  K. Hess, H. Hammerstein and W. Gramberg. (1937).  30.  G. Jayroe and W. Demmig.  31.  A. Klemer and F. Gundlach.  32.  S. Matsubara.  33.  J . Compton.  34.  0. T. Schmidt. (1962).  35.  K. Matsuda, H. Watanabe, K. Fujimoto and K. Aso. 191, 278 (1961).  36.  E. M. Montgomery, N. K. Richtmeyer and C. S. Hudson. Am. Chem. Soc. 6_5, 1848 (1943).  37.  B. Lindberg and L. S e l l e b y . (1960).  38.  I . Johanson, B. Lindberg and 0. Theander. Scand. 17, 2019 (1963).  Ber. 62, 1418 (1929).  Helv. Chira. A c t a . 16, 144 (1933). Nature 3_78, 1222 (1956).  B e r . 61, 137, 1508 (1928). A c t a . Chem. Scand. 3, 1153 (1949). Can. J . Chem.  A c t a . Chem. Scand. _3, 1355 (1949). J . Agr. Chem. Soc. (Japan) J . Chem. Soc. 4264 B e r . 70, 1134  Chem. Ber. j93, 356 (1960). Chem. Ber. j_5, 1765 (1963).  B u l l . Soc. Chem. (Japan) 34, 718 (1961). J . Am. Chem. Soc. 60, 1203 (1938). Methods i n Carbohydrate Chem. 1, 349 Nature J.  A c t a . Chem. Scand. 14, 1051 A c t a . Chem.  -77-  39.  A. P i c t e t and A. M a r f o r t .  40.  P. Karrer and C. Kamienski. (1932).  41.  L. Asp and B. Lindberg.  42.  K. Freudenberg  43.  S. T s u i k i . Tohuku. J . E x p t l . Med. 61, 267 (1955). C.A. _50, 4043 (1956).  44.  J. Stanek and J . Sada. C o l l . Czech. Chem. C o l l . 14, 540 (1949). C.A. 44, 5820 (1950).  45.  Z et.  46.  G. Zemplen and Z. Csuros.  47.  S. Peat.  48.  F. H. Newth.  49.  R. de Souza and I . J . G o l d s t e i n . 1215 (1964).  50.  F. H. Newth, S. D. N i c h o l a s , F. Smith and L. F. Wiggins. J. Chem. Soc. 2550 (1949).  51.  T. L. C o t t r e l l and E. G. V. P e r c i v a l . (1942).  52.  T. J. P a i n t e r .  53.  B. Lythgoe  54.  H. Bredereck.  55.  P. B r i g l and P. M i s t e l e .  56.  B. H e l f e r i c h and W. Ost. Chem. Ber. j95, 2616 (1962).  57.  B. H e l f e r i c h and J . Z i r n e r .  58.  E. F i s c h e r , M. Bergmann and A. Rabe.  59.  B. H e l f e r i c h and W. K l e i n .  60.  B. H e l f e r i c h .  Heweihi.  Helv. Chim. A c t a .  j6, 129 (1923).  Helv. Chim. A c t a . 15, 739 —  A c t a . Chem. Scand. 6, 941 (1952).  and K. S o f f .  Ber. 69, 1245 (1936).  Chem. Ber. 86, 862 (1953). Ber. 62, 993 (1929).  Advan. Carbohydrate Chem. 2, 37 (1946). Quart. Rev. 13, 50 (1959). Tetrahedron L e t t e r s  J . Chem. Soc. 749  J . Chem. Soc. 1596 (1964).  and S. T r i p p e t t .  J . Chem. Soc. 1985 (1950).  Ber. 65, 959 (1930). Z. p h y s i o l Chem. 126, 120 (1923).  Chem. Ber. JJ6, 385 (1963). Ber. J55, 2562 (1920).  Ann. £ 5 0 , 219 (1926).  Advan. Carbohydrate Chem. 5, 79 (1948).  -78-  61.  A. Thompson and M. L. Wolfrom. " E s t e r s " i n "The Carboh y d r a t e s " ( e d i t e d by W. Pigman), Academic Press Inc., New York, N. Y., p. 138 (1957).  62.  F. M i c h e e l . Chemie Der Zucker und P o l y s a c c h a r i d e Akademische V e r l a g s g e s e l l s c h a f t . L e i p z i g p. 102 (1956).  63.  M. L. Wolfrom and A. Thompson. Chemistry 2, 211 (1963).  64.  T. G. Bonner.  65.  D. Horton and D. H. Hutson. 18, 162 (1963).  66.  B. H e l f e r i c h and W. S p e i c h e r .  67.  R. S. Tipson.  68.  C. M. McCloskey.  69.  I . Croon and B. L i n d b e r g .  70.  M. E. Tate and C. T. Bishop.  71.  R. W. J e a n l o z , A. M. C. Rapin, and S. Hakomori. Chem. 26, 3939 (1961).  72.  0. T. Schmidt  73.  H. Bredereck, A. Wagner, G. Faber, H. Ott and J . Rauther. Chem. Ber. 92, 1135 (1959).  74.  M. Smith, D. H. Rammler, I . H. Goldberg and H. G. Khorana. J. Am. Chem. Soc. 84, 430 (1962).  75.  K. Josephson.  76.  Y. H i r a s a k a , I . Matsunaga, K. Umemoto and M. Sukegawa. Yakugaku Z a s s h i . 83, 966 (1963).  77.  R. S u t r a .  78.  G. G. S. Dutton and K. N. S l e s s o r .  79.  H. B o r j e s o n , P. Jerkeman and B. L i n d b e r g . Scand. 17, 1705 (1963).  80.  P. Jerkeman and B. L i n d b e r g . 1709 (1963).  Methods of Carbohydrate  Advan. Carbohydrate Chem. 1J3, 59 (1961). Advan. Carbohydrate Chem. Ann. 579, 106 (1953).  Advan. Carbohydrate Chem. 8, 107 (1953). Advan. Carbohydrate Chem. 1Z,  137 (1957).  A c t a . Chem. Scand. 1Z,  and E. Wernicke.  593 (1959).  Can. J . Chem. 41, 1801 (1963). J . Org.  Ann. 558, 70 (1947).  Ann. 472, 230 (1929).  B u l l . Soc. Chim. 9, 794 (1942). Unpublished R e s u l t s . A c t a . Chem.  A c t a . Chem. Scand. 17,  -79-  81.  H. H. Schlubach, W. Rauchenberger and A. S c h u l t z e . Ber. £ 6 , 1248 (1933).  82.  P. Jerkeman.  83.  E. J . Hedgley and H. G. F l e t c h e r , J r . 84, 3726 (1962).  84.  K. Heyns and H . Paulsen. 169 (1962).  85.  K. Heyns.  86.  M. B a r c z a i - M a r t o s and F. Korosy.  87.  B. H e l f e r i c h and A. Berger.  88.  H. F i s c h e r and F. Kogl.  Ann. £ 3 6 , 219 (1924).  89.  R. Kuhn and H. J . Haas.  Angew. Chem. £ 7 , 785 (1955).  90.  G. Z w e i f e l and H. Deuel.  91.  H. 0. L. F i s c h e r , C. Taube and E. Baer. Ber. £ 0 , 479 (1927).  92.  N. G. G a y l o r d .  93.  R. A l l e r t o n and H. G. F l e t c h e r , J r . J . Am. Chem. Soc. _76, 1757 (1954).  94.  M. E. Tate and C. T. Bishop.  95.  R. W. Jeanloz and A. M. C. Rapin. (1962).  96.  F. Cramer, H. Otterbach and H. Springmann. 92, 384 (1959).  97.  J . H. Chapman and L. N. Owen.  98.  M. A b d u l l a h .  99.  H. H. Baer and H. 0. L. F i s c h e r . 44, 991 (1958).  A c t a . Chem. Scand. .17, 2769 (1963). J . Am. Chem. Soc.  Advan. Carbohydrate Chem. 17,  Staerke 15, 425 (1964). Nature 165, 369 (1950).  Chem. Ber. £ 0 , 2492 (1957).  Helv. Chim. A c t a . 39, 662 (1956).  E x p e r i e n t i a 10, 423 (1954).  Ph.D. T h e s i s .  100.  H. H. Baer and A. Ahammad.  101.  F. ¥. L i c h t e n t h a l e r .  Can. J . Chem. 40, 1043 (1962). J . Org. Chem. "28, 2978 Chem. Ber.  J . Chem. Soc. 579 (1950). U n i v e r s i t y of London  (1960).  Proc. Nat. Acad. S c i .  Can. J . Chem. 41, 2931 (1963).  Angew. Chem. 76, 84 (1964).  -80-  102.  L. D. H a l l and L. Hough.  Proc. Chem. Soc. 382 (1962).  103.  R. E. Reeves.  J . Am. Chem. Soc. ll  104.  A. S. P e r l i n .  Advan. Carbohydrate Chem. 14, 9 (1959).  105.  Ibid.  106.  R. J . Dimler.  107.  R. U. Lemieux and S. L e v i n s .  108.  T. H i r a s a k a .  109.  G. G. S. Dutton and K. N. S l e s s o r . 1110 (1964).  110.  Y. H i r a s a k a , I . Matsunaga, K. Umemoto and M. Sukegawa. Yakugaku Z a s s h i £ 3 , 971 (1963).  111.  Ibid.  112.  R. B e n t l e y , J . Am. Chem. Soc. 81, 1952 (1959).  113.  V. S. R. Rao and J . F. F o s t e r . (1963).  114.  A. E. Knauf, R. M. Hann and C. S. Hudson. Soc. £ 3 , 1447 (1941).  115.  R. M. Hann and C. S. Hudson. (1941).  J . Am. Chem. Soc. 63, 2241  116.  K. Freudenberg and W. Nagai.  Ber. £ 6 , 27 (1933).  117.  W. T. Haskins, R. M. Hann and C. S. Hudson. Soc. £ 4 , 1289 (1942).  118.  ¥ . T. Haskins, R. M. Hann, and C. S. Hudson. Soc. £ 4 , 1852 (1942).  119.  M. L. Wolfrom, R. M. de Lederkremer and L. E. Anderson. A n a l . Chem. £ 5 , 1357 (1963).  120.  M. Gee.  121.  Y. U. Zhdanov, G. A. Korol'chenko and G. N. Dorofeenko. Dokl. Akad. Nauk. SSSR. 143, 852 (1962). C.A. 57, 4747 (1962).  y  2116 (1949).  p. 12. Advan. Carbohydrate Chem. 7, 37 (1952). Can. J . Chem. 4_2, 1473 (1964).  Yakugaku Z a s s h i . £ 3 , 960 (1963). Can. J . Chem. 42,  pp. 1073, 1078.  J . Phys. Chem. 67, 951 J . Am. Chem.  J . Am. Chem. J . Am. Chem.  A n a l . Chem. 35, 350 (1963).  81  122.  J . M. Swan.  Nature 180, 643 (1957).  123.  L. Hough, J . K. N. Jones and ¥. L. Wadman. Soc. 1702 (1950).  124.  R. U. Lemieux and H. F. Bauer.  125.  H. G. Brown and C. A. Brown. (1962).  126.  M. Jackson and L. D. Hayward.  127.  R. D. Guthrie and D. Murphy.  128.  G. W. Hay, B. A. Lewis and F. Smith. 479 (1963).  129.  B. B a n n i s t e r and F. Kagan. (1960).  130.  M. A k a g i , S. Tejima and M. Haga. (Tokyo) 10, 562 (1962).  131.  J . K. N. Jones, R. A. Wall and A. 0. P i t t e t . Chem. J58, 2285 (1960).  132.  E. F i s c h e r and K. Zach.  133.  R. B. Ward.  134.  A. Klemer.  J . Chem.  A n a l . Chem. 2_3, 920 (1954). J . Am. Chem. Soc. 84, 2827 J . Chromatog. _5, 166 (1961). J . Chem. Soc. 5288 (1963). J . Chromatog. 11,  J . Am. Chem. Soc. 82, 3363 — Chem. Pharm. B u l l . Can. J .  Ber. _U5, 3761 (1912).  Methods i n Carbohydrate Chem. 2, 394 (1963). Chem. Ber. 92, 218 (1959).  SYNTHESIS OF THE 2,4-DI-0-METHYL TETROSES  -82-  INTRODUCTION Purpose The  aim of preparing  to f a c i l i t a t e  p a r t i a l l y methylated t e t r o s e s  the i d e n t i f i c a t i o n of small  q u a n t i t i e s of  p a r t i a l l y methylated sugars by c h a r a c t e r i z a t i o n periodate oxidation not  only i n f o r m a t i o n  products.  of t h e i r  Periodate o x i d a t i o n  may supply  on the number of f r e e v i c i n a l h y d r o x y l s  p r e s e n t , but a l s o , a n a l y s i s of the products f o r formic and  formaldehyde gives  information  acid  as to t h e i r l o c a t i o n .  Formaldehyde then, i n d i c a t e s the presence of a primary in a 1,2-glycol  was  alcohol  system, whereas formic a c i d i n d i c a t e s a  secondary a l c o h o l f l a n k e d by two other a l c o h o l  groups.  I d e n t i f i c a t i o n of the fragments might allow f u l l  characterization  of the sugar. Two r e c e n t reference  communications have emphasized the need f o r  compounds i n the t e t r o s e  series.  Had i d e n t i f i c a t i o n  of the t e t r o s e s produced by p e r i o d a t e o x i d a t i o n the  intensive  been p o s s i b l e ,  i n v e s t i g a t i o n necessary to determine the parent  sugar would not have been necessary. Stephen ( l ) , i n h i s s t r u c t u r a l i n v e s t i g a t i o n of V i r g i n i a oroboides gum, used p e r i o d a t e o x i d a t i o n  to e s t a b l i s h the  p o s i t i o n s of s u b s t i t u t i o n on p a r t i a l l y methylated sugars.  -83-  S e v e r a l c h r o m a t o g r a p h i c a l l y f a s t running products were obtained which, from c o n s i d e r a t i o n of the assigned s t r u c t u r e of the parent  sugar, were b e l i e v e d to be of the t e t r o s e s e r i e s .  Stephen a s s i g n e d probable  s t r u c t u r e s f o r these  only a f t e r extensive i n v e s t i g a t i o n of the parent sugar.  products,  to e s t a b l i s h the s t r u c t u r e  P a r t i a l l y methylated  obtained from h y d r o l y s i s of a methylated upon p e r i o d a t e o x i d a t i o n , methylated  glucoses,  glucan  reducing  ( 2 ) , gave, fragments,  b e l i e v e d to be t e t r o s e s . To provide r e f e r e n c e compounds f o r s t r u c t u r a l  determinations  of t h i s type, the s y n t h e s i s of the 2,4-di-0-methyl t e t r o s e s was  undertaken.  Background Tetrose i s the generic name d e s c r i b i n g f o u r carbon The  sugars.  c l a s s of compounds b e l o n g i n g to t h i s f a m i l y , which c o n t a i n  a s t r a i g h t carbon group, possess  chain terminated by an a l d e h y d i c  two asymmetric carbon  functional  atoms and t h e r e f o r e  c o n s i s t s of four s t e r e o i s o m e r i c compounds. The  s y n t h e s i s of t e t r o s e s can be approached from two  directions.  S t a r t i n g with D or L - g l y c e r a l d e h y d e , an ascent  of the s e r i e s can be c a r r i e d out through carbon  a d d i t i o n of a f u r t h e r  atom by v a r i o u s chemical means, i n c r e a s i n g the l e n g t h  of the three carbon  sugar by one.  The other major approach  -84-  is  through degradation of higher carbon  a carbon-carbon  sugars by cleavage of  bond.  Ascent of the s e r i e s can be accomplished by the c l a s s i c a l K i l i a n i s y n t h e s i s ( 3 ) , i n which the aldose i s t r e a t e d with hydrogen cyanide forming a n i t r i l e , which, through and r e d u c t i o n , regenerates an aldehyde  c o n t a i n i n g one more  hydroxy-methylene group than i t s p r e c u r s o r . developed by Sowden and F i s c h e r  hydrolysis  A newer method,  (4, 5 ) , i n v o l v e s the  condensation of the aldose with nitromethane.  Subsequent  h y d r o l y s i s of the n i t r o compound gives the new aldehyde i n good y i e l d . of  An i n h e r e n t drawback i n any method f o r ascent  the s e r i e s i s the i n t r o d u c t i o n of a f u r t h e r  asymmetric  carbon atom i n t o the molecule, g i v i n g r i s e to the p o s s i b i l i t y of  two p r o d u c t s .  G e n e r a l l y , both p o s s i b l e products are  formed, one u s u a l l y i n h i g h e r y i e l d . epimers  The s e p a r a t i o n of these  c o n s t i t u t e s the major drawback to  methods which  i n v o l v e ascent of the s e r i e s . S e v e r a l methods are a v a i l a b l e f o r the degradation of the carbon c h a i n of a sugar. Wohl degradation  A c l a s s i c a l method such as the  (6) r e q u i r e s the e l i m i n a t i o n of hydrogen  cyanide from the oC-hydroxyl n i t r i l e .  A newer method (7)  i n v o l v e s the o x i d a t i o n of d i e t h y l d i t h i o a c e t a l s with p e r acids.  Subsequent treatment with base e l i m i n a t e s the d i s u l f o n e ,  -8 5-  y i e l d i n g an aldehyde of one carbon l e s s .  P r o b a b l y one of  the most u s e f u l and h i g h e s t y i e l d i n g methods i s degradation through g l y c o l cleavage.  Cleavage between s u i t a b l y d i s p o s e d  1.2- d i o l systems by p e r i o d a t e ( 8 ) , or l e s s f r e q u e n t l y l e a d t e t r a a c e t a t e , r e s u l t s i n two aldehydes.  The use of both  of these reagents has been r e c e n t l y reviewed (9, 10).  The  y i e l d s from p e r i o d a t e cleavage are q u a n t i t a t i v e , i n f a c t Malaprade  (8) o r i g i n a l l y i n t r o d u c e d t h i s r e a c t i o n as a method  of q u a n t i t a t i v e l y e s t i m a t i n g p e r i o d a t e .  Limitations i n  degradative methods are r e a l i z e d when i t i s seen that a s u i t a b l y o r i e n t a t e d and s u b s t i t u t e d pentose must be used i n the s y n t h e s i s of a t e t r o s e by the C - l e l i m i n a t i o n method, and t h a t contiguous h y d r o x y l groups should not be p r e s e n t i n a product expected to be produced by g l y c o l cleavage. The chemistry of the twenty-four p a r t i a l l y t e t r o s e s has o n l y been b r i e f l y i n v e s t i g a t e d .  O-methylated  P r i o r to t h i s  work, o n l y three r e p o r t s of s y n t h e t i c p a r t i a l l y methylated t e t r o s e s had been p u b l i s h e d . methyl-D-xylose  P e r i o d a t e o x i d a t i o n of  gave 2-0-methyl-D-threose  (11), and  3-0similarly  2.3- d i - O - m e t h y l - D - a r a b i n i t o l gave 2,3-di-0-methyl-D-threose Although the p r e p a r a t i o n of 3-0-methyl-L-threose has been described  (13), no p h y s i c a l p r o p e r t i e s of the product were  d e s c r i b e d a t t h a t time.  P r e v i o u s workers i n t h i s group have  attempted s y n t h e s i s of 2,3-di-O-methyl-L-threose  (14),  (12).  -86-  2,3-di-O-methyl-D-erythrose (14), 2-0-inethyl-D-erythrose (15), and 2,4-di-O-methyl-L-erythrose (16).  -87-  METHODS OF SYNTHESIS 2,4-Di-O-methyl-D-erythrose The  s y n t h e s i s of 2,4-di-O-methyl-D-erythrose  was  achieved  by p e r i o d a t e o x i d a t i o n of 4 , 6 - d i - O - m e t h y l - D - g l u c i t o l . g l u c i t o l was  prepared by borohydride r e d u c t i o n of  The  4,6-di-0-  methyl-D-glucose. 4,6-Di-O-methyl-D-glucose was of  B e l l and Lorber  4,6-benzylidene blockage of  s y n t h e s i z e d by the method  (17) which depends on the formation of a  group on methyl ^ - D - g l u c o s i d e a l l o w i n g  of hydroxyls 2 and 3 as b e n z y l e t h e r s .  The  lability  the benzaldehyde a c e t a l t o weak a c i d allows p r e f e r e n t i a l  removal of t h i s group. di-O-methyl  Subsequent methylation gives the  derivative.  Reductive  cleavage of the b e n z y l  e t h e r s and a c i d h y d r o l y s i s of the g l y c o s i d e y i e l d the f r e e sugar  (Fig. 1). I t i s i n t e r e s t i n g to note t h a t while B e l l and  Lorber*s  method begins with the r e a d i l y a v a i l a b l e methyl  ^-D-glueoside,  the i n t e r m e d i a t e compounds are e i t h e r s i r u p s or  difficultly  c r y s t a l l i z a b l e compounds.  Dennison and McGilvray (18) on  the other hand, s t a r t with the l e s s common methyl  /S -D-  g l u c o s i d e u s i n g the same sequence of r e a c t i o n s to give the ^-glycoside.  In t h i s anomeric s e r i e s a l l the i n t e r m e d i a t e s  were found to be c r y s t a l l i n e .  This f u r t h e r s u b s t a n t i a t e s  -88CH OH  /0CH  2  0CH  ZnCtg HO'X.OH  OCH-  0C  0CH C1 KOH  0CHO  ^ O C H  \  2  2  OCH  3  2  "0,  H*  OCH 0 y»OCH 2  3  t  OCH 0 2  CH 0H  ;H OCH  2  2  ™"o<  Ag 0 2  = =  CH 3«  TOCH 0  CH 0'\0£H|5/ 0CH 1  3  2  2  3  Na/Hg  H  '  3  OCH 0  2  :H OCH EttOH  3  ^O'X^OH  ./10CH  +  3  OH  9 2 H  O C H  0  3  CH O \ OH 3  l  NaBH4  H,OH  |  CH OH 2  L  HOH  OH  0 H 0CH  3  J-OH  CH 0CH 2  104  0 CH  }-OCH  3  f-OH  CH OCH 2  Fig. I  3  3  -89-  Zemplen's statement are more d i f f i c u l t  (19) t h a t compounds c o n t a i n i n g ^ - l i n k a g e s to c r y s t a l l i z e than  the  corresponding  compounds with the j!> - l i n k a g e . P e r i o d a t e o x i d a t i o n of the reduced glucose r e s u l t e d i n a 2.03 mole of sugar.  4,6-di-0-methyl-D-  molar uptake of p e r i o d a t e per  A f t e r p r e c i p i t a t i o n of the i o d a t e and  p e r i o d a t e as barium s a l t s , the  s o l u t i o n was  excess  evaporated  to  give a s i r u p . C h a r a c t e r i z a t i o n was dinitrophenylhydrazone  achieved by formation of the  and measurement of the o p t i c a l  2,4rotation.  2,4-Di-O-methyl-L-erythro se 2.4- Bi-O-methyl-L-erythrose  was  s y n t h e s i z e d by p e r i o d a t e  o x i d a t i o n of 3 , 5 - d i - O - m e t h y l - L - a r a b i n i t o l . obtained through  the borohydride  This a l c o h o l was  r e d u c t i o n of 3,5-di-0-methyl-  L-arabinose. 3.5- Di-O-methyl-L-arabinose to the procedure  was  synthesized according  of H i r s t , Jones and W i l l i a m s  (20).  This  route r e l i e s on the a c i d s t a b i l i t y of the 5 - t o s y l e s t e r formed by t r e a t i n g an  o(,/3  mixture  with t o s y l c h l o r i d e i n p y r i d i n e . the  replacement  without  of methyl a r a b i n o f u r a n o s i d e s  The  acid s t a b i l i t y  of the methyl g l y c o s i d e with  concurrent r i n g expansion.  In t h i s way  allows  1,2-isopropylidene 1,2-isopropy-  -90-  lidene-5-tosyl-arabinose i s isolated.  Removal of the 5-  t o s y l group by r e d u c t i v e cleavage l e a v e s the 3 and 5 h y d r o x y l s f r e e to be methylated.  A c i d h y d r o l y s i s of the i s o p r o p y l i d e n e  group of the methylated d e r i v a t i v e y i e l d s  3,5-di-0-methyl-L-  arabinose ( F i g . 2 ) . A possible  source of 3,5-di-O-methyl-L-arabinose i s  f u l l y methylated mesquite  gum.  S e v e r a l workers (21, 22)  have h y d r o l y z e d t h i s methylated gum with weak a c i d to cleave the arabinofuranose l i n k a g e s .  The dimethyl sugar was i s o l a t e d  from the h y d r o l y z a t e mixture by f r a c t i o n a l d i s t i l l a t i o n of the methyl  glycosides.  U n f o r t u n a t e l y , t r a c e s of 2,5-di-O-  methyl-L-arabinose aire present i n such p r e p a r a t i o n s (23), and cannot e a s i l y be removed. 2,4-Di-O-methyl-L-erythrose  i s i d e n t i c a l to i t s o p t i c a l  isomer 2,4-di-O-methyl-D-erythrose, except o p t i c a l r o t a t i o n .  i n a l l i t s properties  The s p e c i f i c  r o t a t i o n was equal  i n magnitude but opposite i n sign as would be expected. 2,4-Di-O-methyl-D-threose P e r i o d a t e o x i d a t i o n of 3 , 5 - d i - O - m e t h y l - D - x y l i t o l y i e l d e d 2.4- di-O-methyl-D-threose c r y s t a l l i n e product.  which, upon p u r i f i c a t i o n , y i e l d e d a  The p e n t i t o l was obtained from the known  3.5- di-0-methyl-D-xylose  (24) by borohydride r e d u c t i o n .  -91-  1Q  4~  r  0 CH CH3Q-I H0-| CH OCH (  2  Fig. 2  3  -92-  3,5-Di-O-methyl-B-xylose was of  prepared by the method  Levene and Raymond (24) ( F i g . 3).  with two molecules  D-Xylose was  of acetone i n the presence  condensed  of concentrated  s u l p h u r i c a c i d to give 1,2-: 3 , 5 - d i i s o p r o p y l i d e n e - D - x y l o s e . P a r t i a l h y d r o l y s i s of the d i i s o p r o p y l i d e n e compound with d i l u t e aqueous a c i d y i e l d e d furanose which was  1,2-isopropylidene-D-xylo-  r e c r y s t a l l i z e d f o r the f i r s t  time to  give the pure compound. M e t h y l a t i o n of 1,2-isopropylidene-D-xylofuranose method of Kuhn e_t a l (25) y i e l d e d a s i r u p which was by vacuum d i s t i l l a t i o n .  by the  purified  H y d r o l y s i s of the i s o p r o p y l i d e n e  group with 25$ aqueous a c e t i c a c i d y i e l d e d c h r o m a t o g r a p h i c a l l y pure 3,5-di-0-methyl-B~xylose.  Borohydride  reduction followed  by p e r i o d a t e o x i d a t i o n y i e l d e d 2,4-di-0-methyl-D-threose c r y s t a l l i z e d a f t e r p u r i f i c a t i o n by s i l i c a  which  g e l column chromatog-  raphy. 2,4-Di-O-methyl-L-threose 2,4-Di-O-methyl-L-threose was o x i d a t i o n of the borohydride 0-methyl-L-sorbose. of  Schlubach  acetone  obtained from  r e d u c t i o n product of 1 , 4 , 6 - t r i -  This sugar was  and O l t e r s (26).  the p e r i o d a t e  s y n t h e s i z e d by the method  Condensation  of L-sorbose  yielded 2,3:4,6-diisopropylidene-L-sorbose.  acid hydrolysis yielded  with  Partial  2,3-isopropylidene-L-sorbofuranose  which, upon m e t h y l a t i o n , y i e l d e d the  1,4,6-tri-0-methyl  -94-  derivative.  The  t r i m e t h y l ether was  compound, but no attempt was  obtained as a c r y s t a l l i n e  made to r e c r y s t a l l i z e  to i t s low m e l t i n g p o i n t (m. p. 15-17°).  Acid hydrolysis  of 2 , 3 - i s o p r o p y l i d e n e - l , 4 , 6 - t r i - 0 - m e t h y l - L - s o r b o s e the t r i m e t h y l ether as the f r e e Borohydride  r e d u c t i o n of  i t due  liberated  sugar. 1,4,6-tri-O-methyl-L-sorbose  f o l l o w e d by p e r i o d a t e o x i d a t i o n y i e l d e d 2,4-di-0-methyl-Lthreose  (Fig. 4).  The  s i r u p c o u l d not be induced to c r y s t a l l i z e  even when seeded with i t s o p t i c a l I t i s important such as sorbose may  to note  t h a t r e d u c t i o n of a  y i e l d two  1,4,6-tri-O-methyl-L-sorbose,  isomer.  hexitols.  ketose  In the r e d u c t i o n of  1,4,6-tri-0-methyl-L-gulitol  (or 1 , 3 , 6 - t r i - O - m e t h y l - D - g l u c i t o l ) and l , 4 , 6 - t r i - 0 - m e t h y l - L iditol  (or 1 , 3 , 6 - t r i - O - m e t h y l - L - i d i t o l ) may  be formed.  c o n f i g u r a t i o n of the d e r i v e d t e t r o s e has no b e a r i n g on c o n f i g u r a t i o n of the carbon  The the  atom at p o s i t i o n 2, as i t i s  e l i m i n a t e d i n the o x i d a t i v e cleavage. Silica mixture  g e l t h i n l a y e r chromatography of the r e d u c t i o n  i n d i c a t e d o n l y one major component, the  of which can p o s s i b l y be i n f e r r e d . that borohydride through  stereochemistry  Bragg and Hough have shown  r e d u c t i o n of aldoses and ketoses  the a c y c l i c  staggered z i g - z a g conformation  Tri-O-methyl-L-sorbose,  proceeds (27).  when represented i n t h i s f a s h i o n  1,4,6-  -95-  -96-  ( F i g . 5), has the b u l k y paper.  Approach  methoxyl  of the borohydride w i l l come then, predominantly,  from below the plane of the paper. the newly formed The d e r i v a t i v e  above the plane of the  Such a t t a c k w i l l leave  h y d r o x y l group above the plane of the  so formed  r e p r e s e n t e d i n F i g . 5.  paper.  i s 1 , 4 , 6 - t r i - O - m e t h y l - L - i d i t o l as Since evidence of the c o n f i g u r a t i o n  of carbon atom 2 i s not e a s i l y o b t a i n e d , the v a l i d i t y of t h i s p r e d i c t i o n cannot be e v a l u a t e d .  -97-  X0H,CH 0CH  H0  CH OH C 3  0CH  2  2  3  3  CH OCH 2  3  Ho^ hOCH:  HO  CH OCH 2  3  H OCH,  \r  CH,OCH~  ^ c  /  \  C  H OH '  CH OCH 3  /  C  C  \  CH 0CH 2  3  H OH  H  2  9  3  OCH-2  H • OH  „C  C CH OCH  C  2  H OH  H OH  CH OCH T-OH 2  HO'  3  •OCH3 CH OCH 2  3  Fig.  5  3  -98-  DISCUSSION Incomplete P e r i o d a t e Oxidation of Reducing Sugars Incomplete p e r i o d a t e o x i d a t i o n of reducing sugars has been reported  (1) and was  s u b s t a n t i a t e d i n t h i s work.  The  reason  f o r t h i s r e s i s t a n c e to p e r i o d a t e o x i d a t i o n i s l i k e l y due  to  the formation of f o r m y l e s t e r s and c y c l i c i n n e r a c e t a l s . Oxidative cleavage aldofuranose the sugar.  of the C - l carbon  of an aldopyranose  or  sugar y i e l d s a formyl e s t e r s t i l l a t t a c h e d to The removal of t h i s formyl e s t e r must precede  any cleavage  t h a t i n v o l v e s the e s t e r i f i e d h y d r o x y l .  Inner  c y c l i c a c e t a l s have been shown to form (28) whenever a f r e e that i s , the  aldehyde  hemiacetal formed c o n t a i n s a s i x membered r i n g . way  a h y d r o x y l group which would be expected  cyclic  In t h i s  to undergo  p e r i o d a t e o x i d a t i o n can be i n a c t i v a t e d by the formation  of  such an i n n e r a c e t a l . Stephen ( 1 ) , circumvented  the danger of formyl e s t e r  formation by r e d u c t i o n of the f r e e sugar to the hexitol.  corresponding  In a s i m i l a r manner, to o b t a i n t h e o r e t i c a l p e r i o d a t e  uptake values i n the s y n t h e s i s of the 2,4-di-0-methyl t e t r o s e s , i t was  found necessary  to reduce the f r e e sugar to the  a l c o h o l p r i o r to the g l y c o l  cleavage.  -99  One  of the most convenient methods of reducing sugars i s  treatment with aqueous sodium borohydride. earlier  As d i s c u s s e d  (see page 94 ) Bragg and Hough (27) have shown that  borohydride r e d u c t i o n i s preceded by opening of the into i t s acyclic  z i g - z a g conformation.  In t h i s  sugar  conformation  any b u l k y s u b s t i t u e n t i n the p o s i t i o n f u n c t i o n w i l l r e t a r d the r a t e of r e d u c t i o n . t h i s to the s t e r i c hindrance of approach  They a t t r i b u t e  of the borohydride  ion to the 1,3-system. Although 3 - 0 - s u b s t i t u t e d a l d o s e s c o n s t i t u t e the m a j o r i t y of examples of such r a t e r e d u c t i o n , 4 - 0 - s u b s t i t u t e d ketoses belong to t h i s s t e r e o c h e m i c a l c l a s s and T h i s was  show the same e f f e c t .  d i s c u s s e d e a r l i e r i n the r e d u c t i o n of l , 4 , 6 - t r i - 0 -  methyl-L-sorbose. In the p r e p a r a t i o n of 3 , 5 - d i - 0 - m e t h y l p e n t i t o l s from parent pentoses  and l , 3 , 6 - t r i - 0 - m e t h y l h e x i t o l s from 1,4,6-  t r i - O - m e t h y l - L - s o r b o s e , borohydride r e d u c t i o n was a f t e r 24 hours.  not  complete  I f l o n g e r times were used, d e t e c t a b l e amounts  of degradation products were formed; due  the  these were, presumably,  to Lobry de Bruyn - van E k e n s t e i n t r a n s f o r m a t i o n s .  Reductions were c a r r i e d out o v e r n i g h t and subsequent of the product from the unreduced chromatography on a s i l i c a azeotrope as the s o l v e n t .  m a t e r i a l was  separation  effected  by  g e l column u s i n g butanone-water  -100-  Chromatography The use of s i l i c a who  g e l columns o r i g i n a t e d with B e l l (29),  estimated the chain l e n g t h of methylated p o l y s a c c h a r i d e s  by use of t h i s method.  E l u t i o n of the f u l l y  methylated  sugars, f o r m e r l y non-reducing end groups, allowed e s t i m a t i o n of  the r a t i o of non-reducing end group  to backbone r e s i d u e s .  With the advent of c e l l u l o s e chromatography, the use of silica  g e l columns was  neglected.  as d e s c r i b e d i n t h i s work, s i l i c a  In p u r i f i c a t i o n s ,  such  g e l column chromatography  o f f e r s comparable r e s o l u t i o n i n approximately one-fourth of  the time.  I t should be noted that t h i n l a y e r chromatography  i s a f a s t , e f f i c i e n t method of a n a l y z i n g methylated fractions gel  (30) obtained from e i t h e r c e l l u l o s e or  silica  columns. Because the importance  lies  sugar  of p a r t i a l l y methylated  i n t h e i r chromatographic  recognition,  tetroses  and R Q  values were recorded i n a l a r g e number of s o l v e n t systems (Table 1 ) .  -J. CI-  TABLE I Physical properties of 2,4-di-O-methyI tetroses 2,4-Di-O-methyl D-erythrose  2,4-Di-O-methyl L-erythrose  Sirup  Sirup -61.4° (c, 4.< in MeOH)  Melting point [<*]D of free sugar  60.1° (c, 1.4 in MeOH)  2,4-Dinitrophenylhydrazone melting point  105-106°  107-108°  R 0.70, 0.64 Ro 0.86, 0.78  Silica gel T. L. C. R 0.62, 0.50  2,4-Di-O-methyl D-threose 114-116° (dimer?) - 1 4 . 8 ° (e, 1.17 in MeOH) - 9 ° (3 min) -> + 0.9° (15 min)  (c, 0.35 in 1 iVHjSOO  Solvent system Butanone Water Azeotrope  2,4-Di-O-methyl L-threose Sirup - 1 4 . 3 ° (c, 5.7 in MeOH) - 1 7 ° (5 min) -> - 3 ° (15 min)  (c, 0.55 in 1 ATHjSOO  14S-149  149-150°  R 0.66, 0.57 R 0.89, 0.76  Silica gel T. L. C. R 6.65, 0*.50  0  1  Ethyl acetate Pyridine Water (8:2:1)  F  F  0  F  RF 0.77 Ro 0.92  Butan-l-ol RF 0.82 Ethanol Ro 0.96 Water (4:1:5) upper layer Ethyl acetate Acetic acid RF 0.80, 0.75 Formic acid Water Ro 0.95, 0.SS (18:3:1:4)  F  0.81 Ro 0.96 RF  R 0.84 Ro 0.98 F  RF  0.86, 0.75  Ro 1.02, 0.S8  ^Descending paper chromatography was carried out using Whatman No. 1 paper and Ro values are relative to 2.3,4,0 tetra-Omethyl-D-glucose. Sugars were detected by use of p-anisidine trichloracetate spray reagent. Optical isomers showed identical chromatographic patterns in all solvents. RF and Ro values quoted for D-threose refer to the sirup before crystallization. The crystalline modification gave only the slower running component. Ascending silica gel thin-layer chromatography was adopted for rapid examination of column fractions. Detection was achieved by use of 6% H N O i in HiSO*. Subsequent heating at 150 was sufficient for development.  -102-  Anomalous Behaviour of O p t i c a l Isomers Paper chromatography of the t e t r o s e s i n some and  chromatography on a s i l i c a  the e x i s t e n c e  Upon standing  g e l t h i n - l a y e r system i n d i c a t e d  of two m o d i f i c a t i o n s  were i n s e p a r a b l e  by s i l i c a  of the t e t r o s e s , which  g e l column chromatography.  f o r extended lengths  of time (3 months),  s i r u p y t e t r o s e s were observed to become more Infrared  spectra  the c a r b o n y l  of the v i s c o u s  viscous.  s i r u p showed r e d u c t i o n i n  s t r e t c h i n g band a t 1750 cm""^ and enhancement  of the h y d r o x y l band at 3400 cm~^", with respect mobile s i r u p .  to the more  The i n f r a r e d spectrum of the c r y s t a l l i n e  2,4-di-0-methyl-D-threose showed no carbonyl band but contained  stretching  a hydroxyl band which was s p l i t  two e q u a l - i n t e n s i t y absorptions The  solvents  into  a t 3375 and 3480 cm"^.  anomalous o p t i c a l r o t a t i o n of the threose isomers (D,  -14.8°; existence  L, -14.3°) i n methanol i s a t t r i b u t e d to the of two or more m o d i f i c a t i o n s  present i n the  s o l u t i o n of the s i r u p y L-threose compound.  Upon s o l u t i o n  of the isomers i n 1 N s u l p h u r i c a c i d , the r o t a t i o n s dropped to near-zero values with opposite  signs.  These  r e s u l t s suggest that 2,4-di-0-methyltetroses e a s i l y undergo dimerization that from (31)  to a compound of s t r u c t u r e  s i m i l a r to  5 -aldo -l,2-0-isopropylidene-D -xylo pentofuranose  (Fig. 6).  The s t r u c t u r e of the c r y s t a l l i n e  modification  103-  of Z,4-di-0-methyl-D-threose a c e t a l nature ( F i g . 7 ) .  may t h e r e f o r e be of a c y c l i c Thin l a y e r chromatography of  the t e t r o s e s i s o l a t e d as s i r u p s contained a p p r e c i a b l e q u a n t i t i e s of m o d i f i c a t i o n s of t h i s type.  Because of  the small amounts of product, molecular weight and n u c l e a r magnetic resonance s t u d i e s were not undertaken.  -104-  H0^  H  C <\ OH CH 0"i H-C -\ CH OGH J-Q/ 0CH CH OCH 1  3  2  3  2  Fig J  3  '  3  -105-  Derivative s Attempts to prepare  c r y s t a l l i n e d e r i v a t i v e s of the  g l y c i t o l s were u n s u c c e s s f u l . p - n i t r o b e n z o a t e s were prepared  Although  some a c e t a t e s and  and shown to be homogeneous  by t h i n - l a y e r chromatography (32), c r y s t a l l i z a t i o n c o u l d not be  induced. Acceptable  a n a l y t i c a l values were seldom obtained f o r the  sirupy di-O-methyltetroses solvent.  presumably because of occluded  No attempt was made  to d i s t i l them because of the  small amounts obtained and t h e i r v o l a t i l i t y . reagents  Several d i f f e r e n t  were t r i e d f o r c h a r a c t e r i z i n g the t e t r o s e s but o n l y  2,4-dinitrophenylhydrazine  gave s a t i s f a c t o r y  d e r i v a t i v e s i n a l l four cases.  crystalline  T h i s reagent was used i n  n e u t r a l s o l u t i o n to give the phenylhydrazone r a t h e r than the osazone.  In r e t r o s p e c t , the d i f f i c u l t y of making c r y s t a l l i n e  d e r i v a t i v e s may be due to the e q u i l i b r i u m with a dimeric form.  -106-  EXPERIMENTAL Evaporations were c a r r i e d out under reduced pressure at a bath temperature of 40-45°.  O p t i c a l r o t a t i o n s are e q u i l i b r i u m  values measured on e i t h e r a Bendix ETL-NPL Automatic P o l a r i m e t e r (Type 143 A) or a Rudolph P o l a r i m e t e r  (Model 219) a t 21 i 2°.  M e l t i n g p o i n t s quoted are u n c o r r e c t e d .  Periodate  oxidation  e s t i m a t i o n s were c a r r i e d out by quenching o x i d a t i o n  aliquots  i n b u f f e r e d a r s e n i t e and b a c k - t i t r a t i n g with i o d i n e . system A: butanone  Solvent  - water azeotrope.  P r e p a r a t i o n of the S i l i c a Gel Column To s i l i c a  g e l ( F i s h e r S-157, 200 g) that had been  screened to pass through 60 mesh was added butanone azeotrope to  (500 ml) with s t i r r i n g .  The s l u r r y was allowed  s i t f o r 1 hour with o c c a s i o n a l s t i r r i n g .  was then s l u r r i e d i n t o a column  - water  The mixture  (3 x 36 cm), f i t t e d with a  f r i t t e d d i s k , and the s i l i c a was packed t i g h t l y by tapping the  outside of the column  apparent. top  u n t i l no f u r t h e r s e t t l i n g  was  A 1 cm l a y e r of sand was c a r e f u l l y p l a c e d on  of the s i l i c a g e l . The column was e q u i l i b r a t e d by p a s s i n g butanone  azeotrope through the column t h i s time the flow r a t e was  f o r two days.  - water  At the end of  constant at 1.8 ml per minute.  The movement of the s o l v e n t can be approximated with Sudan IV dye which shows an R_> of about 0.95  on t h i n  layer  -107-  plates.  Using t h i s as a marker the f r o n t time f o r the column  was about 1 hour. F r a c t i o n s from the column were analyzed by running samples on s i l i c a  g e l t h i n l a y e r p l a t e s using the same solvent  system as that used on the column. S y n t h e s i s of 2,4-Di-O-methyl-D-erythrose 4,6-Di-O-methyl-D-glucose 4,6-Di-O-methyl-D-glucose was prepared by the method of B e l l and Lorber (17).  A f t e r r e c r y s t a l l i z a t i o n from e t h y l  a c e t a t e the constants were: m.p. 70.5° ( c , 1.23 1 0  8°  154-156  i n HgO). L i t .  °. C°0  n  116°  *  >- 65.7° ( c , 4 i n H 0 ) . g  4,6-Di-O-methyl-D-glucitol 4,6-Di-O-methyl-D-glucose  (1,3-Di-O-methyl-L-gulitol) (2.7 g) was d i s s o l v e d i n water  (50 ml) and sodium borohydride (0.5 g) was added.  The  solution  was n e u t r a l i z e d with a c e t i c a c i d a f t e r 18 hours, and evaporated to dryness.  The r e s u l t i n g s o l i d was  t r e a t e d with Z% HG1 i n  methanol (3 x 15 ml) and evaporated to dryness.  The r e s i d u e  was d i s s o l v e d i n water (25 ml) and the s o l u t i o n d e - i o n i z e d with Amberlite IR-120 ( H ) and D u o l i t e A-4 f  the r e s u l t i n g s o l u t i o n  (0H~).  E v a p o r a t i o n of  gave a non-reducing s i r u p  (2.6 g ) ,  -108-  4,6-Di-0-methyl-D-glucitol  Phenylurethan  To 4,6-di-O-methyl-D-glucitol was  added phenylisocyanate  heated was  (100 mg)  (0.3 ml) and  on a steam bath f o r 3 hours.  i n p y r i d i n e (1  the s o l u t i o n  ml)  was  Anhydrous methanol (1  ml)  added and h e a t i n g continued f o r a f u r t h e r 15 minutes.  The cooled s o l u t i o n was  poured dropwise i n t o c o l d water (25  and the p r e c i p i t a t e f i l t e r e d . acetone  R e c y r s t a l l i z a t i o n from e t h a n o l -  gave a product m e l t i n g a t 195-199°.  l i z a t i o n from e t h y l acetate - petroleum  By  recrystal-  ether (30-60°)  the m e l t i n g p o i n t c o u l d be r a i s e d to 203-205°.  The mixed  m e l t i n g p o i n t with d i p h e n y l u r e a  depressed  (m.p.  n i t r o g e n analyses were always high. N, 8.16$.  Found: N, 9.57,  ml)  238°) was  but  Calculated for 3 g g _ o 4 C  H  0  N  J  3  9.61$.  2,4,Di-0-methyl-D-erythrose 4,6-Bi-0-methyl-D-glucitol (25 ml) was  added to 0.12  The o x i d a t i o n was 2.03 was  (524 mg,  2.5 mmoles) i n water  M sodium p e r i o d a t e (50 ml, 6 mmoles).  complete i n 25 minutes with an uptake of  moles of p e r i o d a t e per mole of h e x i t o l .  The  solution  n e u t r a l i z e d with washed barium carbonate, and d i l u t e d with an  equal volume of methanol, f i l t e r e d and evaporated a mobile silica  to give  s i r u p which was  p u r i f i e d by chromatography on a  g e l column to give  2,4-di-0-methyl-D-erythrose  (297 rag)  1.4  i n MeOH).  -109-  2 ,4-Dinitrophenylhydrazone of 2 ,4-Di-0-methyl-D-erythrose 2.4- Di-O-methyl-D-erythrose  (100rag)was d i s s o l v e d i n 100$  ethanol (5 ml) and r e c r y s t a l l i z e d 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e (110 mg) was added.  The mixture was r e f l u x e d on a steam  bath f o r 5 hours, evaporated to dryness, d i s s o l v e d i n e t h y l acetate  (10 ml) and petroleum ether (30-60°) (10 ml) was added  to p r e c i p i t a t e excess reagent. 10 minutes, the f i l t r a t e chloroform  The mixture was f i l t e r e d  after  evaporated to a s i r u p , d i s s o l v e d i n  (2 ml) and a p p l i e d to an alumina column (3 x 20 cm).  C o l l e c t i o n of the l i g h t yellow band e l u t e d with c h l o r o f o r m a f f o r d e d yellow-orange c r y s t a l s m e l t i n g at 102-103°.  Subsequent  r e c r y s t a l l i z a t i o n from e t h y l acetate - petroleum ether (3060°) gave c r y s t a l s m e l t i n g at 105-106°. C  1 2  H  1 6  0 N : N, 17.07; 7  4  OCHj, 18.90$.  Calculated f o r  Found: N, 17.04;  0CH , 5  19.23$. S y n t h e s i s of 2,4-Di-0-methyl-L-erythrose 3.5- Di-0-methyl-L-arabinose 3,5-Di-O-methyl-L-arabinose  was obtained by the procedure  of H i r s t , Jones and W i l l i a m s (20).  The s i r u p showed o n l y one  component (R^ 0.59) upon paper chromatography 6.7 i n MeOH). 39° (25$ aqueous a c e t i c  acid).  i n solvent  Lit.  (20),  system D  -110-  3,5-Di-O-methyl-L-arabinonolactone 3,5-Di-0-methyl-L-arabinose  (75 mg)  i n water  (4 ml)  was  t r e a t e d with bromine (4 drops) and the mixture l e f t  at room  temperature  silver  overnight.  A e r a t i o n and treatment with  carbonate f o l l o w e d by f i l t r a t i o n  gave a s o l u t i o n which  was  passed through IR-120 (H*), and evaporated to a s i r u p . Sublimation at 65-70° (0.05 mm)  gave c r y s t a l s of 3,5-di-0-  methyl-L-arabinonolactone, m.p.  72-73°.  L i t . (20), m.p.  73°.  3,5-Di-O-methyl-L-arabinonamide 3,5-Di—O-methyl-L-arabinonolactone i n methanol was  left  (6 mg)  was  s a t u r a t e d with ammonia (1 ml) and the  o v e r n i g h t at room temperature.  evaporated to give c r y s t a l s , which a f t e r from acetone, melted at 144°.  dissolved solution  The s o l u t i o n  was  recrystallization  L i t . (20), m.p.  144°.  3,5-Di-O-methyl-L-arabinitol (1,3-Di-O-methyl-L-lyxitol) 3,5-Di-O-methyl-L-arabinose (30 ml) was left  (1.7 g) d i s s o l v e d i n water  t r e a t e d with excess sodium borohydride (1 g) and  at room temperature  overnight.  The s o l u t i o n was  up i n the same manner as d e s c r i b e d f o r glucitol.  The  sirup containing  and 3,5-di-O-methyl-L-arabinose completely on the s i l i c a  worked  4,6-di-0-methyl-D-  3,5-di-0-methyl-L-arabinitol ( c a . 9:1)  g e l column.  was  separated  The arabinose (R_«  0.56  -111-  T.L.C. same s o l v e n t system) was found i n the e l u a t e , 175-300 mis a f t e r the dye marking  the f r o n t .  The a r a b i n i t o l  (R^ 0.40) was found i n the 675-1000 ml f r a c t i o n .  Evaporation  of the f r a c t i o n c o n t a i n i n g a r a b i n i t o l y i e l d e d a non-reducing sirup  (1.4 g)  J  D  -7° ( c , 5.8 i n C H C l j ) .  2.4- Di-O-methyl-L-erythrose 5.5- D i - O - m e t h y l - L - a r a b i n i t o l (527 mg, 2.93 mmoles) i n water  (200 ml) was t r e a t e d with 0.08 M sodium p e r i o d a t e  (50 ml, 4.0 mmoles).  The o x i d a t i o n was complete  i n 10 minutes  and was worked up as d e s c r i b e d f o r i t s o p t i c a l isomer.  The  f i n a l p e r i o d a t e uptake was 1.04 moles per mole of p e n t i t o l . P u r i f i c a t i o n on s i l i c a D  g e l gave a c o l o u r l e s s s i r u p  (365 mg)  -61.4° ( c , 4.85 i n MeOH).  2,4-Dinitrophenylhydrazone of 2,4-Di-0-methyl-L-erythrose The hydrazone  was prepared u s i n g the same q u a n t i t i e s as  that f o r i t s o p t i c a l isomer, g i v i n g c r y s t a l s , which upon r e c r y s t a l l i z a t i o n from e t h y l a c e t a t e - petroleum e t h e r (30-60°), melted a t 107-108°. 0CH , 18.90$. 3  C a l c u l a t e d f o r C_ H_g0_N :  Found: N, 16.97;  2  4  0CH , 19.08$. 3  N, 17.07;  -112-  Synthesis of 2,4-Di-Q-methyl-D-threose l,2-Isopropylidene~D-xylofuranose 1,2-Isopropylidene-D-xylofuranose acid hydrolysis product was  r e c r y s t a l l i z e d from e t h y l acetate 67-69°  in H 0).  41-43°  H 0). 2  L i t . (33), m.p.  Calculated f o r C H g  C, 50.68;  prepared by  of l , 2 : 3 , 5 - d i i s o p r o p y l i d e n e - D - x y l o s e .  ether (30-60°) (1:4) m.p. 2  was  H,  1 4  0 : C, 50.52;  The  petroleum  H, 7.57$.  5  the  Found?  7.65$.  3,5-Di-0-methyl-l,2-isopropylidene-D-xylose 1,2-Isopropylidene-B-xylofuranose method of Kuhn ejb a l (25). s i r u p , which was  The  was  methylated  compound was  by  the  i s o l a t e d as a  d i s t i l l e d under vacuum, c o l l e c t i n g the f r a c t i o n  b o i l i n g a t 80-82° (0.05 rotation  mm).  The mobile 5.2  l i q u i d had a s p e c i f i c  i n CHC1 ).  L i t . (34),  3  3,5-Di-0-methyl-D-xylose 3,5-Di-0=methyl-l,2-isopropylidene-D-xylose dissolved  i n 25$  aqueous a c e t i c a c i d and heated  bath f o r 5 hours a f t e r which time constant.  After  component (Rf 0.57)  was  on a steam  the o p t i c a l r o t a t i o n  evaporation a yellow s i r u p  which showed only one  (5 g)  was.  (2.1 g) remained  upon paper  -113-  chromatography in H 0). 2  i n s o l v e n t system A, Q ^ - ^ ]  L i t . (34),  25° ( c , 1.13  D  p-Bromophenylosazone  of  p 23.5° (£, in  3.9  HO).  5,5-Di-O-methyl-D-xylose  The osazone was prepared by the method of A p p l e g a r t h , Dutton and Tanaka  (55).  5,5-Di-O-methyl-D-xylose  and p-bromophenylhydrazine glacial acetic acid  (280 mg)  (4.5 ml).  (75  mg)  were d i s s o l v e d i n  Water (2.2 ml) was  added  and the s o l u t i o n heated 6 minutes on a steam bath and allowed to c o o l .  A f t e r 2 hours at 5° the c r y s t a l s were f i l t e r e d  and r e c r y s t a l l i z e d from e t h y l acetate - petroleum ether (3060°) (1:7) m.p.  106.5-107.5°.  5,5-Di-0-methyl-D-xylitol 5,5-Di-0-methyl-D-xylose (15 ml) was  L i t . (24), m.p.  107-108°.  (l,3-Di-0-methyl-L-xylitol) (590 mg)  d i s s o l v e d i n water  t r e a t e d with excess sodium borohydride (200  mg).  The s o l u t i o n was l e f t at room temperature o v e r n i g h t , and worked up i n the manner d e s c r i b e d f o r the a r a b i n i t o l . sirup  (550 mg)  ^oC\  The  obtained showed no reducing p r o p e r t i e s  -5.4° ( c , 6.6  i n CHClg).  2.4- Di-0-methyl-D-threose 3.5- D i - 0 - m e t h y l - D - x y l i t o l (212 mg, (40 ml) was mmoles).  1.17  mmoles) i n water  t r e a t e d with 0.203 M p e r i o d i c a c i d  The o x i d a t i o n was  (10 ml,  2.03  complete i n 10 minutes and the  -114-  f i n a l p e r i o d a t e uptake amounted to 0.91 pentitol. for of  Work up was  moles per mole of  i d e n t i c a l to that d e s c r i b e d  the e r y t h r o s e s to give a mobile s i r u p t h i s m a t e r i a l on a s i l i c a  g e l column  ( d i m e r i c ? ) 2,4-di-O-methyl-D-threose.  earlier  (124 mg).  yielded  Purification  crystalline  Recrystallization  e t h y l a c e t a t e - petroleum ether (30-60°) (1:5) gave  ---->• 0.9° C  6 12°4 H  C  :  (15 min)  »  H, 8.22;  4 8  »  6 4  J  H  ( c , 0.35 >  8.11;  i n 1 N HgS0 ). 3  crystals  Calculated f o r  4  0CH , 41.89$.  from  Found:  C, 48.78;  0CH , 41.51$. 3  2,4-Dinitrophenylhydrazone of  2,4-Di-O-methyl-D-threose  The hydrazone was prepared i n the same manner and u s i n g the  same q u a n t i t i e s as f o r the 2,4-di-0-methyl  erythroses.  The d e r i v a t i v e a f t e r r e c r y s t a l l i z a t i o n from e t h y l acetate petroleum ether (30-60°) melted a t 148-149°. C  12 16°7 4 H  N  J  N  >  17.07;  0CH , 18.90$. 3  Calculated f o r  Found: N, 17.26}  0CH , 5  18.43$. S y n t h e s i s of 2,4-Di-0-methyl-L-threose 2,3-Isopropylidene-l,4,6-tri-O-methyl-L-sorbose 2,3-Isopropylidene-l,4,6-tri-0-methyl-_-sorbose was prepared by the method of Schlubach and O l t e r s  (26).  Vacuum  distillation  -115-  (0.05  mm) gave a f r a c t i o n b o i l i n g at 1 0 5 - 1 1 5 ° .  crystallized  upon being kept i n a f r e e z e r  months,  15-17°.  m.p.  CKJ  D  * °  2 9  6  (  -'  1  ,  0  (-10°)  No attempt was made to  t h i s m a t e r i a l . \^<^-J  D  i  n  34.2° C H C 1  (c,  4.05  The s i r u p for  six  recrystallize  i n C;HC1 ).  Lit.  3  (26),  3 * )  1,4,6-Tri-O-methyl-L-sorbose 1,4,6-Tri-O-methyl-L-sorbose hydrolysis (26).  was prepared by m i l d a c i d  of- 2 , 3 - i s o p r o p y l i d e n e - l , 4 , 6 - t r i - 0 - m e t h y l - L - s o r b o s e  The s i r u p showed o n l y one component  (R^ 0.72  paper chromatography i n s o l v e n t system A.^ 3.16° in  (c,  7.2  i n CHC1-).  L i t . (26),  D  3 . 8 ° (c,  1.5  5  or  (1,3,6-Tri-O-methyl-D-glucitol  1,3,6-Tri-O-methyl-L-iditol)  1,4,6-Tri-O-methyl-L-sorbose was t r e a t e d overnight  at room temperature.  resulting silica  (520 mg) i n water (15  with excess sodium borohydride  i s o l a t e d i n the  The methylated  same manner as p r e v i o u s l y  gel  t h i n l a y e r chromatography using  h e x i t o l s were  described.  1.5  in  on  s o l v e n t system A.  was i s o l a t e d by chromatography on a  CHC1-).  The  (R^. 0.45)  column to give a s i r u p (280 mg) having a r o t a t i o n (c,  ml)  (1 g) and l e f t  s i r u p showed o n l y one major component  T h i s component  5.6°  ^ -1.85°—»~  CHC1 ). 1,4,6-Tri-O-methyl-hexitol  gel  upon  silica ^  -116-  2,4-Di-O-methyl-L-threose To the t r i - O - m e t h y l h e x i t o l (650 mg, i n water  (5 m l ) , 0.2  was added.  M sodium p e r i o d a t e  The o x i d a t i o n  an uptake of 0.98  was  (20 ml, 4.0  mmoles)  complete i n 5 minutes with  moles of p e r i o d a t e per mole of h e x i t o l .  Recovery of the t e t r o s e  i n the manner d e s c r i b e d  subsequent p u r i f i c a t i o n on a s i l i c a colourless  2.9 mmoles) d i s s o l v e d  g e l column  above and yielded a  sirup  2,4-Dinitrophenylhydrazone of 2,4-Di-0-methyl-L-threose The hydrazone was prepared using  the same q u a n t i t i e s  as  that of i t s o p t i c a l isomer, g i v i n g the d e r i v a t i v e , which upon r e c r y s t a l l i z a t i o n from e t h y l acetate - petroleum ether (50-60°) melted a t 149-150°. N, 17.07j  0CH , 18.90$. 3  Calculated  for  Found: N, 16.87;  c  ig  H 1 6  °  N 7  4  s  OCHj, 19.16$.  -117BIBLIOGRAPHY 1.  A. M. Stephen.  J . Chem. Soc. 2030 (1962).  2.  G. G. S. Dutton and A. M. Unrau. (1963).  3.  H. K i l i a n i .  4.  J . C. Sowden and H. 0. L. F i s c h e r . 1963 (1947).  5.  J . C. Sowden.  6.  A. Wohl.  7.  D. L. MacDonald and H. 0. L. F i s c h e r . 74, 2087 (1952).  8.  L. Malaprade.  9.  J . M. B o b b i t t .  Can. J . Chem. 41, 2439 —  Ber. 18, 3066 (1885). J . Am. Chem. Soc. 69, —  Advances i n Carbohydrate Chem. 6, 291 (1951).  Ber. _26, 730 (1893).  Bull.  Soc. chim.  J . Am. Chem. Soc.  (France) 43, 683 (1928).  Advances i n Carbohydrate Chem. 11, 1 (1956).  10.  A. S. P e r l i n .  Advances i n Carbohydrate Chem. 14, 9 (1959).  11.  G. W. Huffman, B. A. Lewis, F. Smith and D. R. S p r i e s t e r s bach. J . Am. Chem. Soc. _77, 4346 (1955).  12.  I . J . G o l d s t e i n , H. Sorger-Domenigg and F. Smith. Chem. Soc. 81, 444 (1959).  13.  K. G a t z i .  14.  K. E. P i e r r e . (1962).  15.  S. C. Ho. (1959).  16.  A. E. B a r l a y . M.Sc. T h e s i s . Columbia. (1961).  17.  D. J . B e l l and J . Lorber.  18.  J . C. Dennison (1951).  19.  G. Zemplen and Z. Bruckner. Ber. 64, 1852 (1931) as quoted in: W. L. Evans, D. D. Reynolds anc[ E. A. T a l l e y . Advances i n Carbohydrate Chem. 6, 27 (1951).  Helv. Chim. Acta. M.Sc. T h e s i s .  B.Sc. T h e s i s .  J . Am.  21, 195 (1938). U n i v e r s i t y of B r i t i s h  U n i v e r s i t y of B r i t i s h  Columbia.  Columbia.  U n i v e r s i t y of B r i t i s h  J . Chem. Soc. 453 (1940).  and D. I . M c G i l v r a y .  J . Chem. Soc. 1616  -118-  20.  E. L. H i r s t , J . K. N. Jones and E. W i l l i a m s . Soc. 1062 (1947).  J . Chem.  21.  J . I . Cunneen and F. Smith.  22.  E. V. White.  23.  S. A. Black and G. G. S. Dutton.  24.  P. A. Levene and A. L. Raymond. 331 (1933).  25.  R. Kuhn, I . Low and N. Trischman.  26.  H. H. Schlubach and P. O l t e r s .  27.  P. D. Bragg and L. Hough.  28.  M. Guernet, A. Jurado-Soler and P. Malangeau. Soc. chim. (France) 1183 (1963).  29.  D. J . B e l l .  30.  G. W. Hay, B. A. Lewis and F. Smith. 479 (1963).  31.  R. S c h a f f e r and H. S. I s b e l l . 3864 (1957).  32.  M. E. Tate and C. T. Bishop.  33.  0. Svanberg  34.  R. A. Laidlaw.  35.  D. A. A p p l e g a r t h , G. G. S. Dutton and Y. Tanaka. J. Chem. 40, 2177 (1962).  J . Chem. Soc. 1146 (1948).  J . Am. Chem. Soc. 68, 272 (1946). Unpublished J. B i o l .  results.  Chem. 102,  Ber. j_0, 203 (1957).  Ann. _550, 140 (1942).  J . Chem. Soc. 4347 (1957). Bull.  J . Chem. Soc. 473 (1944).  and K. Sjoberg.  J . Chromatog. 11,  J . Am. Chem. Soc. 79, Can. J . Chem. 40, 1043 (1962), Ber. j56, 863 (1923).  J . Chem. Soc. 2941 (1952). Can.  

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0062249/manifest

Comment

Related Items