INHIBITION OF N-ACETYLGLUCOSAMINYLTRANSFER ENZYMES - CHEMICAL-ENZYMATIC SYNTHESIS OF NEW 5-MEMBERED ACETAMIDO AZASUGARS

Two new acetamido azasugars have been synthesized and tested as inhibitors of beta-N-acetylglucosaminase. Ozonolysis of enantiomerically pure N-(4-phenyl-2-azido-3-butenyl)acetamide, derived from cinnamic aldehyde, followed by lipase-catalyzed resolution of the amine intermediate 5, gave 2-azido-3-acetamidopropanal which was then condensed with dihydroxyacetone phosphate by using FDP-aldolase. The condensed product was dephosphorylated and hydrogenated to afford the five-membered acetamido azasugar analogous to N-acetylglucosamine. Compounds 1 and 2 prepared in this manner were new competitive inhibitors of a beta-N-acetylglucosaminidase with K(i) values of 1.9 and 3.6 muM, respectively, and could be useful for the synthesis of N-acetylglucosaminyltransferase inhibitors.