Fructose-1,6-bisphosphate aldolase-mediated synthesis of aminocyclitols (analogues of valiolamine) and their evaluation as glycosidase inhibitors

Lahssen El Blidi (1) , Zeinab Assaf (1) , Flora Camps Bres (1) , Henri Veschambre (1) , Vincent Thery (1) , Jean Bolte (1) , Marielle Lemaire (1)

1 SEESIB - Synthèse et étude de systèmes à intêret biologique

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 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 -glucosidase and -galactosidase

Mots clés: cyclitols; enantioselectivity; enzymes; glycosylation; inhibitors

Lahssen El Blidi, Zeinab Assaf, Flora Camps Bres, Henri Veschambre, Vincent Thery, et al.. Fructose-1,6-bisphosphate aldolase-mediated synthesis of aminocyclitols (analogues of valiolamine) and their evaluation as glycosidase inhibitors. ChemCatChem, 2009, 1, pp.463-471. ⟨hal-00438420⟩