Fructose-1,6-Bisphosphate Aldolase-Mediated Synthesis of Aminocyclitols (Analogues of Valiolamine) and their Evaluation as Glycosidase Inhibitors

摘要

A highly stereoselective method for the preparation of nitro-and aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldoi reaction of dihydroxyacetone phosphate (DHAP) on hydroxynitrobutanals, is reported. The key part of the synthesis is based on a one-pot /two-enzyme process whereby three reactions take place; rabbit muscle aldolase (RAMA) catalyzed aldolization, phytase-catalyzed phos- phate hydrolysis, and intramolecular spontaneous nitroaldoliza-tion. Two families-of nitrocyclitols were obtained depending on the carbon configuration in the β position to the nitro group. Reduction of the latter afforded the aminocyclitols. Evaluation of the inhibition properties of the amines towards five commercially available glycosidases has shown selectivity for |3-glucosidase and β-galactosidase.