(+/-)-6-ACETAMIDO-1,2-ANHYDRO-6-DEOXY-MYO-INOSITOL - A TIGHT-BINDING INHIBITOR AND PSEUDOSUBSTRATE FOR N-ACETYL-BETA-GLUCOSAMINIDASES

A five-step procedure is described for the synthesis of the title compound (N-acetylconduramine B trans-epoxide, 14) from tetra-O-acetylconduritol B [(+/-)-(1,3/2,4)-1,2,3,4-tetra-0-acetyl-5-cyclohexene-1,2,3,4-tetrol]. Inhibition studies with N-acetyl-beta-glucosaminidases from bovine kidney, jack beans, and Helix pomatia gave K(i) values for 14 of 0.50-1.6 muM, i.e., 500-8000-fold lower than the K(i) for 2-acetamido-2-deoxy-D-glucose. The K(i) values for N-acetylconduramine B [(+/-)-(1,3/2,4)-4-acetamido-5-cyclohexene-1,2,3-triol] and its cis-epoxide [(+/-)-1-acetamido-2,3-anhydro-2-deoxy-myo-inositol] were several orders of magnitude larger than for 14. In contrast to the interaction of other glycosidases with anhydro-inositols of appropriate configuration, there was no covalent, irreversible inhibition. Instead, the first two enzymes catalysed a transformation of 14 into a compound (presumably the oxazoline) which underwent spontaneous hydrolysis at pH less-than-or-equal-to 5. No inhibition was observed with the N-acetyl-beta-glucosaminidase from Aspergillus niger.