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

Comprehensive Summary N , 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.