UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Glycos-3-Y1 amino acids : synthetic studies of structural analogs of the polyoxin complex Dooley, Kent Cosford


The syntheses of glycos-3-yl amino acids, 2-deoxy glycos-3-yl amino acids,and deoxy amino uronic acid derivatives (homologous of the sugar moiety of the polyoxins) are reported. 5,3-Spiro-pyrrolidone carbohydrate derivatives, formed by intramolecular cyclization from doubly branched-chain a, y-diami.no acids, are also described. The ketose, 1,2:5,6-di-O-isopropylidene-a-D-ribo-hexofuranos-3-ulose (8)'', was condensed with 2-phenyl-5 (4)-oxazolinone (89), in the presence of lead (II) acetate as catalyst, to yield (E)-and (Z)-2-phenyl-4- (1,2:5,6-di-O-isopropylidene-a-D-ribo-hexofuranos-3-ylidene)-5(4) oxazolone (143) and (144), as a 1:1 mixture,in a 75% yield. The stereo-specific synthesis of 143 was achieved by changing the reaction solvent from dimethoxyethane to tetrahydrofuran. Methanolysis of a mixture of 143 and 144 afforded a mixture of (E)- and (Z)-methyl-N-benzamido-a-(1,2:5,6-di-O-isopropylidene-a-D-ribo-hexofuranos-3-ylidene)glycinate (145) and (146) in a 90% yield. Catalytic hydrogenation of the mixture of 145 and 146 afforded methyl-D-2 (and L-2) -3-deoxy-1,2 :5 ,6-di-0_-isopropylidene-a-D-allofuranos-3-yl)-N-benzoylglycinate (147) and (148) which were separated by silica gel chromatography. Methyl 4,6-0-benzylidene-2-deoxy-q-D-erythro-hexopyranoside-3-ulose (153), was allowed to react with 2-phenyl-5(4)-oxazolone (89) to yield (E)- and (Z)-2-phenyl~4-(methyl-4,6-0-benzylidene-2,3-dideoxy-a-D-erythro-hexopyranos-3-ylidene)-5(4)-oxazolone (154) and (155) in 13% and 27% yields, respectively. Methanolysis of 154 and 155_ afforded (Eland (Z)-methyl-N-benzamido-a-(methyl-4,6-0-benzylidene-2,3-dideoxy-a-D-erythro-hexopyranos-3-ylidene)glycinate (156) and (157) in quantitative yields. Compound 156 was catalytically"hydrogenated to afford methyl-D-2-(methyl-4,6-0-cyclohexylmethylidene-2,3-dideoxy-q-g-arabino-hexopyranos-3-yl)-N-cyclohexylcarboxylglycinate (167) in a 71% yield. Similarly, _15_7 afforded methyl-D-2- (methyl-4 ,6-0-cyclohexylmethylidene-2 , 3-dideoxy-q-D-ribo-hexopyranos- 5-yl) -N-cyclohexylcarboxylglycinate (170) in a 68% yield. 2-Phenyl-5(4)-oxazolone (89) was condensed with 3-0-benzyl-l,2-O-isopropylidene-q-g-xylo-pentodialdo-1,4-furanose (173), prepared by known procedures, to afford a mixture of (E)- and (Z)-4-(3-0_-benzyl-5-deoxy-1,2-0-isopropylidene-q-D-xylofuranos-S- ylidene)-2-phenyl-5(4)-oxazolone (174) and (175) in a 45% yield. Methanolysis of the mixture of 174 and 175 afforded (E)- and (Z)-methyl-6-N-benzamido-3-0-benzyl-5,6-dideoxy-l,2-0-isopropylidene-q-D-xylo-heptofur-5-enuronate (176) and (177) in an 85% yield. Hydrogenation followed by hydrogenolysis of the mixture of 176 and 177 gave a mixture of methyl-6-N-benzamido-5,6-dideoxy - 1,2-0-isopropy'lidene-a-D-gluco (and g-L-ido) -heptofuranuronat (180) and (181) . Transesterification of 180 and 181 afforded the ethyl esters which were separated into pure ethyl-6-N-benzamido-5,6-dideoxy-1,2-0-isopropylidene-a-D-gluco (and g-L-ido)-heptofuranuronate (182) and (183) by fractional crystallization. Compound 183 was hydrolyzed in hot aqueous ethanolic barium hydroxide solution to afford 6-amino-5,6-dideoxy-1,2-0-isopropylidene-g-L-ido-heptofuranuronic acid (184) in a 77% yield. The 1,3-dipolar addition of diazomethane to (Z)-3-deoxy-1,2:5,6-di-0-isopropylidene-3-C-methoxycarbonylmethylene-a-g-ribo-hexofuranose (13) , prepared from 8_ by application of the Wittig reaction, afforded a mixture of spiro-AA- and A^-pyrazolines, which were hydrogenated at high pressure with Raney nickel, to afford spiro-3,4'-S_- (3,3-dideoxy-1,2:5,6-di-O-isopropylidene-q-p-ribo-hexofuranose)-3'-R-amino-2'-pyrrolidone (192) , spiro-3,4'-S~(3,3-dideoxy-l,2:5,6~di-0-isop ropy lidene-a-D-ribo--hexo furanose)-3'-S_-amino-2'pyrrolidone (195) , spiro- 3,4' - R- (3, 3-dideoxy-l ,2 :5 ,6-di-^-isopi'opylidene-a-D-ri_bo_-hexofuranose)-3'-R-amino-2'-pyrrolidone (194) , and spiro-3,4*-R-(3, 3-dideoxy-1,2:5,6-di-0-isopropylidene-a-p-ribo-hexofuranose)- 3'-S-amino-2'-pyrrolidone (195) in yields of 16, 32, 14, and 18%^respectively. Compounds 192, 195, 194, and 195 were acetylated to yield the crystalline derivatives 196, 197.. 198, and 199, Selective de-0-i sop ropy l.i den at ion of compound 196 followed by oxidative cleavage with sodium meta-periodate gave an aminal 200 which was acetylated to afford spiro-3,4' -S_- (3, 3-dideoxy- 1,2-0-isopropylidene-a-D-erythro-pentodia.ldo-1,4-furanose)-3'-R-acetamido-2'-pyrrolidone 3',5 - R-aminal-5,1'-diacetate (202). Compound 19 7 was^selectively de-O-isopropylidenated and oxidized with periodate to yield spiro-3 ,4 '-S-(3,3-dideoxy--1,2-0-isopropylidene-a-D-erythro-pentodialdo-1,4-furanose) -3' -S_- acetamido-2 ' -pyrrolidone (201) . Complete de-0_-isopropylidenation of 197 afforded spiro- 3,4'-S_~ (3,3-dideoxy-g-D-ribo-hexopyranose) -3' -S_-acetamido-2 ' -pyrrolidone (203) in a 30% yield. An optically active amino acid Wittig reagent was prepared as follows. L-Cystine diethyl ester dihydrochloride (205) was chlorinated to yield 3-chloro-L-alanine ethyl ester hydrochloride (206) which was converted to N-acetyl-g-chloro-L-alanine ethyl ester (207). Compound 207 was reacted with tr:i phenyl nhosplunc and sodium iodide to afford cthyl-N-acetyl-3- (triphenyJphosphoniuiniodo)-a-L-a] an ate (204) in a 51% yield.

Item Media

Item Citations and Data


For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.