title: 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 alpha-galactosidase (Ki = 1.7 microM). Similarly compounds 6 (Ki= 28 microM), ent-5 (Ki= 129 microM), and ent-6 (Ki= 12 microM) exhibited specific inhibition of beta-glucosidase.
authors.affiliation: Division of Organic Chemistry (Synthesis) and Division of Biochemical Science, National Chemical Laboratory, Pune-411008, India. gp.pandey@ncl.res.in
authors.forename: Ganesh
authors.initials: G
authors.lastname: Pandey
authors.forename: Shrinivas G
authors.initials: SG
authors.lastname: Dumbre
authors.forename: M Islam
authors.initials: MI
authors.lastname: Khan
authors.forename: M
authors.initials: M
authors.lastname: Shabab
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; D006026:Glycoside Hydrolases