Fructose-1,6-Bisphosphate Aldolase-Mediated Synthesis of Aminocyclitols (Analogues of Valiolamine) and their Evaluation as Glycosidase Inhibitors
ElBlidi, Lahssen . 2009
A highly stereoselective method for the preparation of nitro and aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldol 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 phosphate hydrolysis, and intramolecular spontaneous nitroaldolization. Two families of nitrocyclitols were obtained depending on the carbon configuration in the b 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 β-glucosidase and β-galactosidase.
Chemoenzymatic dynamic kinetic resolution (DKR) of amines involving sulfanyl radical-induced racemization happened to be the very first switchable DKR process allowing the…
A highly stereoselective method for the preparation of nitro and aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldol reaction of dihydroxyacetone phosphate (DHAP)…