1. A concise synthesis of N-substituted fagomine derivatives and the systematic exploration of their α-glycosidase inhibition.
- Author
-
Jiang FX, Liu QZ, Zhao D, Luo CT, Guo CP, Ye WC, Luo C, and Chen H
- Subjects
- Crystallography, X-Ray, Cyclization, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Glycoside Hydrolase Inhibitors chemical synthesis, Glycoside Hydrolase Inhibitors chemistry, Imino Pyranoses chemical synthesis, Imino Pyranoses chemistry, Molecular Docking Simulation, Molecular Structure, Structure-Activity Relationship, Enzyme Inhibitors pharmacology, Glycoside Hydrolase Inhibitors pharmacology, Imino Pyranoses pharmacology, alpha-Glucosidases metabolism
- Abstract
A novel and concise scheme has been developed successfully for the syntheses of N-substituted fagomine derivatives. The transformation of lactone (2) to 1,5-diol (3) was carried on with high yield (93-95%). The cyclization of 4 to 5 is a high stereoselective reaction (de value > 98%). It is disclosed that bulky substituent at N atom of the piperidine decreases the inhibition activity except those substituents having the ability of solvation or forming disulfide bond with M444 at the active site of α-glycosidase, which enhance the interaction with enzyme. Compounds with S-configuration at C-3 show greater activity than those with R-configuration. The structure-activity relationship study is also supported by molecular docking analysis., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF