Aldolase-catalyzed C-C bond formation for stereoselective synthesis of nitrogen-containing carbohydrates

Abstract

Rabbit muscle aldolase was found to catalyze stereoselective aldol addition of dihydroxyacetone phosphate (1) to 3-azido-2-hydroxypropana(2 ). The ketose 1-phosphates were isolated as barium salts, 4a/4b, and hydrolyzed with acid phosphatase. The mixture of 6-azido-6-deoxy-D-fructose(5) and 6-azido-6-deoxy-L-sorbose thus obtained was separated by anion-exchange chromatography. Reductive amination of 5 and 6 yielded, respectively, 1-deoxymannojirimycin (7) and 1-deoxynojirimycin (8), with high diastereoselectivity (>98:2). Analogous aldol addition of 1 to 3-azido-2-hydroxybutanal( 9)( E:Z = 92:8) afforded a mixture of the 6-azido-6,7-dideoxyheptuloses 12 and 13, which contained 88% of 6-azido-6,7-dideoxy-D-altro-heptulose(13 ). After anion-exchange chromatography, 13 was isolated as a 18:82 mixture of the β/α anomers. Reductive amination of pure 13 gave a mixture of 2,6,7-trideoxy-2,6-imino-D-glycero-D-manno and D-gluco-heptitol (14 and 15) (3:2 molar ratio), which likewise was separated by anion-exchange chromatography. If a mixture of 12 and 13 was hydrogenated under identical conditions, 2,6,7-trideoxy-2,6-imino-L-glycero-L-gulo-heptitol(16) could be isolated besides 14 and 15.