Chemoenzymatic Synthesis of N,N,N‐Trimethyl‐D‐Glucosamine Chitotriomycin and Its Analogues

Abstract

Comprehensive SummaryN,N,N‐Trimethyl‐D‐glucosamine (TMG)‐chitotriomycin, a naturally occurring chitin related oligosaccharide, is a specific β‐N‐acetylhexosaminidases (HexNAcases) inhibitor for insects and fungi. Although TMG‐chitoriomycin holds great promise as a novel class insecticide and fungicide, the limited accessibility of TMG‐chitotriomycin prevents its further biological evaluation. We report herein a simple and eco‐friendly chemoenzymatic approach for the efficient synthesis of TMG‐chitotriomycin and its analogues. In this strategy, the readily available chitosan was enzymatically hydrolyzed and chemically N‐acetylated to afford the chitooligosaccharides ranging from disaccharide to hexasaccharide. These chitooligosaccharides were selectively deacetylated by two different chitin deacetylases followed by chemical N‐trimethylation to obtain the desired TMG‐chitotriomycin and a total of 13 TMG‐chitotriomycin analogues in the longest linear sequence of 4 steps in over 12% total yields.