Convergent Approach toward the Synthesis of the Stereoisomers of C-6 Homologues of 1-Deoxynojirimycin and Their Analogues: Evaluation as Specific Glycosidase Inhibitors

A new and stereoselective strategy is developed to synthesize an appropriate template 9 to obtain C-6 homologues of 1-deoxyazasugars such as 1-deoxy-d-galactohomonojirimycin (5), 1-deoxy-4-hydroxymethyl-d-glucohomonojirimycin (6), and their enantiomers. The template 9 is also used to obtain neutral nonbasic pseudo-glyconolactam (8), C-4 amino, and methyl analogues of 1-deoxy-homonojirimycin as new analogues of 1-deoxyhomoazasugars. Compound 5 is found to be a potent and specific inhibitor to α-galactosidase (Ki = 1.7 μM). Similarly compounds 6 (Ki = 28 μM), ent-5 (Ki = 129 μM), and ent-6 (Ki = 12 μM) exhibited specific inhibition of β-glucosidase.