Inhibition of glycosidases by aldonolactones of corresponding configuration: Preparation of (1→5)-lactones by catalytic oxidation of pyranoses and study of their inhibitory properties

Abstract

1. A method was devised for the preparation of (1-->5)-lactones from pyranose sugars and uronic acids by platinum-catalysed oxidation with gaseous oxygen in aqueous solution at acid pH. It was applied to mannose, N-acetylglucosamine, N-acetylgalactosamine, glucuronic acid, galacturonic acid, galactose, l-arabinose and d-fucose. 2. Only the first three yielded products that could be obtained in the solid state without decomposition. In every case, however, the oxidation product in aqueous solution behaved as the aldono-(1-->5)-lactone, and was more inhibitory towards the appropriate glycosidases than any aldonolactone preparation hitherto examined. 3. The stabilities of the oxidation products were studied, and their interconversion with the (1-->4)-lactones was demonstrated. Ring-opening does not appear to be mandatory for this isomeric change, which in some instances is very rapid. 4. To explain all the inhibitory effects observed with aldonolactones on glycosidases of corresponding configuration, it is tentatively postulated that inhibition may be due entirely to the (1-->5)-lactone, and that any inhibitory effect seen with the (1-->4)-lactone is a measure of the extent and speed of its conversion into the (1-->5)-lactone in aqueous solution.