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Synthesis and Inhibition Study of Bicyclic Iminosugar‐Based Alkaloids, Scaffolds, and Libraries towards Glucosidase
Author(s) -
Cheng WeiChieh,
Guo ChihWei,
Lin ChengKun,
Jiang YuRuei
Publication year - 2015
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.201400140
Subject(s) - iminosugar , chemistry , bicyclic molecule , pyrrolidine , stereochemistry , substituent , combinatorial chemistry , organic chemistry , enzyme
A small library of bicyclic iminosugar‐based alkaloids and scaffolds possessing a polyhydroxylated pyrrolidine and a varied ring skeleton have been synthesized. Through rapid diversification of the scaffold via an amide coupling with random carboxylic acids, structurally diverse bicyclic iminosugar‐based libraries were prepared with substituent diversity, core diversity, and configurational diversity. This discovery process allowed us to efficiently sieve out potent and specific glycosidase inhibitors, and a bicyclic, conformationally restricted iminosugar was demonstrated to be more potent than the monocyclic ones in this study. The most potent and selective inhibitor discovered was found to have a K i value of 71 nM against α‐glucosidase.