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UBC Theses and Dissertations

Branched-chain sugar nucleosides Nguyen, Laure Marie Kim-Khanh


A new route to branched-chain sugars by application of a modified Wittig reaction to ketoses has been developed. 3-Deoxy-3-C-(2'-hydroxyethyl)-1,2:5,6-di-O-isopropylidene-α-D-allofuranose (LXVII) was prepared from 1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose (I) and subsequently used as key intermediate in the synthesis of two novel branched-chain sugar nucleosides. Selective hydrolysis of (LXVII) to the 1,2-0-monoisopropylidene derivative (LXXII) followed by benzoylation and acetolysis yielded 1,2-di-0-acetyl-2’ ,5,6-tri-0-benzoyl-(2'-hydroxyethyl)-β-D-allofuranose (LXXIV). Condensation of this compound with chloromercuri-6-benzamidopurine in the presence of titanium tetrachloride and subsequent deblocking with methanolic sodium methoxide afforded the branched-chain sugar nucleoside 9-[3'-deoxy-3'-C-(2"-hydroxyethyl)-β-D-allofuranosyl]-adenine (LXXXIII) in 48% yield based on (LXXIV). In a separate procedure, 3-C-(carbomethoxymethyl)-3-deoxy-l, 2 :5,6-di-O-isopropylidene-α-D-allofuranose (LXI) was selectively hydrolyzed to afford 3-C-(carbomethoxymethyl)-3-deoxy-l,2-0-isopropylidene-α-D-allofuranose (LXXXIV). Sodium metaperiodate degradation of the latter followed by reduction with sodium borohydride yielded 3-deoxy-3-C-(2'-hydroxyethyl)-1,2-O-isopropylidene-α-D-ribofuranose (LXXXV). In a procedure parallel to that used for the preparation of nucleoside (LXXXIII) compound (LXXXV) was converted to the branched-chain nucleoside 9-[3'-deoxy-3'-C-(2"-hydroxyethyl)-β-D-ribofuranosyl]-adenine (LXXXVIII) in 37% yield based on the diacetate. The oxo reaction was applied to the unsaturated sugar 3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-erythro-hex-3-enose (II) in an attempt to prepare a branched-chain sugar having a hydroxymethyl group on C-3. In an endeavor to find a better method for the synthesis of compound (II), 1,2:5,6-di-0-isopropylidene-3-0-p-tolylsulfonyl-α-D-glucofuranose (XXIV) was reacted with a tetramethylammonium hydroxide solution in dimethyl sulfoxide and shown to yield quantitatively 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose. Under similar conditions, the 3-0-p-nitrobenzenesulfonate ester of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (LXXXIX) gave 3-0-[p- (3-deoxy-1,2:5,6-di-0-isopropylidene-α-D-glucofuranose-3-yl) oxyphenylsulfonyl]-1,2:5,6-di-0-isopropylidene-α-D-glucofuranose (XC) and l,2:5,6-di-0-isopropylidene-3-0-p-nitrophenyl-α-D-glucofuranose (XCI). A discussion of the probable mechanism of this reaction is based on a study of the products obtained by application of the same reaction to ethyl p-nitrobenzenesulfonate. The reaction of 3-deoxy-1,2:5,6-di-0-isopropylidene-α-D-erythro-hex-3-enose (II) with carbon monoxide and hydrogen (in the ratio of 1:3) in the presence of dicobalt octacarbonyl gave eight products. Hydrogenolysis of the 5,6-0-isopropylidene group occurred as evidenced by n.m.r. and g.l.c. of the volatile portion of the oxo mixture. When (II) was allowed to react with carbon monoxide and hydrogen (6:1), part of the starting material rearranged to afford a substance (XCIX) in 25% yield which was presumed to be a 2,3-ene. Reduction of the remaining oxo product with sodium borohydride followed by acetylation gave after separation by g.l.c. two crystalline components in a ratio of 1:6.

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