AMINOSUBSTITUTED ALPHA-D-GLUCOSYLMETHYLBENZENES (BENZYL ALPHA-C-GLUCOSIDES) AND AN N-(C-ALPHA-D-GLUCOSYLMETHY)ANILINE (ANILINOMETHYL ALPHA-C-GLUCOSIDE) - NOVEL ALPHA-D-GLUCOSIDASE INHIBITORS

D-Glucose was transformed via 3,4,5,7-tetra-O-benzyl-1,2-dideoxy-D-gluco-hept-1-enitol (5) into 2,6-anhydro-3-4-5,7,tetra-O-benzyl-1-C-phenyl-D-erythro-L-ido-heptitol (9) the structure of which was determined by X-ray analysis of the per-O-acetylated derivative 12. 1-O-Mesylation of 9 and azide displacement gave only low yields of 2,6-anhydro-7-azido-1,3,4,5-tetra-O-benzyl-7-deoxy-7-C-phenyl-D-erythro-L-gulo-heptitol (16). Therefore, 9 was oxidized to 2,6-anhydro-3,4,5,7-tetra-O-benzyl-1-C-phenyl-D-glycero-D-ido-heptose (15) and thence transformed into the (E/Z)-oximes 17h,l which, with LiAlH4 as reducing agent, gave 7-amino-2,6-anhydro-1,3,4,5-tetra-O-benzyl-7-deoxy-7-C-phenyl-D-erythro-L-gulo-heptitol (19), 7-amino-2,6-anhydro-1,3,4,5-tetra-O-benzyl-7-deoxy-7-C-phenyl-L-threo-L-gulo-heptitol (23), and 2,6-anhydro-1,3,4,5-tetra-O-benzyl-7-deoxy-7-phenylamino-D-glycero-L-gulo-heptitol (27) in 1:1:1 ratios. Their N-protection, hydrogenolytic O-debenzylation, and N-deprotection afforded the desired target molecules 7-amino-2,6-anhydro-7-deoxy-7-C-phenyl-D-erythro-L-gulo-heptitol (1a), 7-amino-2,6-anhydro-7-deoxy-7-C-phenyl-L-threo-L-gulo-heptitol (2a), and 2,6-anhydro-7-deoxy-7-phenyl-amino-D-glycero-L-gulo-heptitol (4a). Hydrogenolysis of 15 furnished directly 2,6-anhydro-7-deoxy-7-C-phenyl-D-glycero-L-gulo-heptitol (3a). Inhibition studies with alpha-D-glucosidase from yeast with p-nitrophenyl alpha-D-glucopyranoside as substrate exhibited, for 1a and 4a, K-i values of the same order as found for 1-deoxynojirimycin.