Amino acid-catalyzed asymmetric carbohydrate formation: Organocatalytic one-step de novo synthesis of keto and amino sugars

A direct de novo synthesis of ketoses and amino sugars by amino acid-catalyzed asymmetric aldol, Mannich and Michael reactions with dihydroxyacetone phosphate mimics as donors is presented. Proline, proline derivatives and thiazolidine-4-carboxylic acids catalyzed the asymmetric assembly of keto sugars and amino sugars in high yield with up to > 99% ee. The organocatalytic C-3+C-n, methodology presented herein is a direct entry to the de novo synthesis of orthogonally protected C-4, C-5, and C-6 ketoses, carbohydrate derivatives, amino and aza sugars and the total synthesis of polyoxamic acids. The addition of water significantly accelerated and improved the enantioselectivity of the proline-mediated biomimetic asymmetric C-C bond-forming reactions.