Aldolase-Catalyzed C-C Bond Formation for Stereoselective Synthesis of Nitrogen-Containing Carbohydrates

Article abstract of DOI:10.1021/jo00299a043

Rabbit muscle aldolase was found to catalyze stereoselective aldol addition of dihydroxyacetone phosphate (1) to 3-azido-2-hydroxypropanal (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 (6) 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 88percent of 6-azido-6,7-dideoxy-D-altro-heptulose (13).After anion-exchange chromatography, 13 was isolated as a 18:82 mixture of the α/β anomers.Reductive amination of pure 13 gave a mixture of 2,6,7-trideoxy-2,6-imino-D-glycero-D-manno- and D-gluco-heptitols (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.