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 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.
Pandey
Ganesh
G
Division of Organic Chemistry (Synthesis) and Division of Biochemical Science, National Chemical Laboratory, Pune-411008, India. gp.pandey@ncl.res.in
Dumbre
Shrinivas G
SG
Khan
M Islam
MI
Shabab
M
M
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
D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; D006026:Glycoside Hydrolases