Modifications of lincomycin involving the carbohydrate portion. Part II. Analogues with D-gluco- and D-ido-stereochemistry

Abstract

Preferential O-butyroylation of the antibiotic lincomycin followed by O-methylsulphonylation led to the 2,3,7-tri-O-butyrate 4-O-methanesulphonate. Reaction with sodium benzoate in NN-dimethylformamide occurred with inversion of configuration at C-4; transesterification gave the gluco-analogue of the antibiotic. Protection of the hydroxy-groups of lincomycin at C-3 and C-4 by acetonide formation and at C-7 by O-triphenylmethylation, followed by O-methylsulphonylation and mild acidic hydrolysis, gave lincomycin 2-O-methanesulphonate. This sulphonate reacted with basic nucleophiles, via the talo-epoxide, to yield exclusively analogues of ido-stereochemistry. The influence of such stereochemical changes on antibacterial activity in this series is discussed.