Chemical synthesis of UDP-4-O-methyl-GlcNAc, a potential chain terminator of chitin synthesis

Abstract

Chitin synthase converts uridine diphosphoryl-N-acetylglucosamine (UDP-GlcNAc) to chitin (poly-beta-(1-->4)-GlcNAc). During polymerization, elongation occurs at the 4-OH (nonreducing) terminus of the growing chitin chain. Blockage of the 4-OH via incorporation of UDP-N-acetyl-4-O-methylglucosamine (UDP-4-OMe-GlcNAc, 3) can potentially terminate chitin polymerization, and represents a novel strategy for chitin synthase inhibition. The chemical synthesis of 3 and preliminary evaluation of its possible incorporation by chitin synthase are reported herein.