65(P40) 分子内グリコシル化反応を利用したヌクレオシド抗生物質の合成(ポスター発表の部)

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The synthesis of cytosamine, a common skeleton of the amicetin family of antibiotics, is described herein. Amicetin was isolated from the fermentation broth of various species of Streptomyces and Aethrobactor in the early 1950s. At present, a total of about ten compounds bearing closely related structures have been found. However, as for the synthetic approach to these compounds, only one total synthesis of plicacetin, one of the amicetin family, was accomplished by Stevens et al. in 1972. Our synthetic study of cytosamine was undertaken to develop the stereoselective formation of 2',3'-dideoxyhexopyranosyl nucleoside employing intramolecular glycosylation. The substrates for the intramolecular glycosylation, 6a and 6b, were prepared starting from commercially available glucal 1 as illustrated in Scheme 1. Using thus obtained 6a, the intramolecular glycosylation was conducted by activation with Me_2S(SMe)BF_4 in the presence of MS4A in MeCN at -20℃. After basic hydrolysis, the desired nucleoside 7a was obtained in 56% yield along with 23% of a C1-hydrolyzed by-product 8a (Scheme 2). By contrast, with starting from 6b, the hydrolysis at C1 was suppressed and the yield of nucleoside 7b was improved to 79%. Next, deoxygenation of the 6' position of 7a and 7b was examined (Scheme 3). The best result was obtained from a reaction sequence starting with the 4-O-MPM derivative 7b. That is, treatment of 7b with I_2-PPh_3 in pyridine provided a 6'-iodo derivative 10b, which was then reduced with Bu_3SnH in the presence of AIBN in refluxing toluene to afford 11b in 70% overall yield. Removal of the MPM group in 11b using DDQ led to compound 12 in 93% yield. Phenyl 4-azido-4,6-dideoxy-1-thio-D-glucoside 18 was synthesized from galactose pentaacetate 13 in 9 steps with 43% overall yield (Scheme 4). Compound 18 was converted into glycosyl fluoride 19, which was then subjected to glycosylation of nucleoside 12 in the presence of AgOTf-SnCl_2 as a promoter to provide disaccharide nucleoside 20 in 50% yield with an α-configuration. Since compound 20 is convertible into cytosamine according to the literature, the formal synthesis of cytosamine was accomplished.
1997-07-20

65(P40) 分子内グリコシル化反応を利用したヌクレオシド抗生物質の合成(ポスター発表の部)

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