Synthesis of 2-(N-acetylamino)-2-deoxy-C-glucopyranosyl nucleosides as potential inhibitors of chitin synthases

The C-glucopyranosyl nucleosides (1-4) containing the N-acetyl glucosaminyl and uridine units have been synthesized as nonhydrolyzable substrate analo gues of UDP-GlcNAc aimed to inhibit the chitin synthases: The key intermedi ate, 4-(2'-(N-acetylamino)-3',4',6'-tri-O-benzyl-2'-deoxy-alpha-D-glucopyra nosyl)but-2-enoic acid (5), was prepared from the perbenzylated (N-acetylam ino)-alpha-C-allylglucoside (7), by successive oxidative cleavage, Wittig o lefination, and ester deprotection. The coupling of the acid 5 with the hyd roxyl or amine function of the uridine derivatives (6a or 6b) afforded, res pectively, the ester 12 and amide 14. The dihydroxylation of the conjugated double bond in ester 12 or amide 14 was better achieved with osmium tetrao xide/barium chlorate, leading to the expected diols 13 and 15 as a mixture of two diastereoisomers. The desired compounds 1-4 were obtained after cata lytic hydrogenation of compounds 12-15.