Convergent approach toward the synthesis of the stereoisomers of C-6 homologues of 1-deoxynojirimycin and their analogues: evaluation as specific glycosidase inhibitors

Abstract

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 (K_i = 1.7 μ M). Similarly compounds 6 (K_i = 28 μ M), ent-5 (K_i = 129 μ M), and ent-6 (K_i = 12 μ M) exhibited specific inhibition of β -glucosidase.