Inhibition of N-Acetylglucosaminyltransfer Enzymes: Chemical-Enzymatic Synthesis of New Five-Membered Acetamido Azasugars

Article abstract of DOI:10.1021/jo00070a013

Two new acetamido azasugars have been synthesized and tested as inhibitors of β-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 dephospharylated 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 β-N-acetylglucosaminidase with K_i values of 1.9 and 3.6 μM, respectively, and could be useful for the synthesis of N-acetylglucosaminyltransferase inhibitors.