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Divergent Synthesis of Bicyclic Iminosugars: Preparation of (−)‐Swainsonine‐Based Alkaloids and Their Inhibition Study towards α ‐Human Mannosidases
Author(s) -
Chen WeiAn,
Sayyad Ashik,
Chen ChiaoWen,
Chen YuHsin,
Cheng TingJen R.,
Cheng WeiChieh
Publication year - 2019
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201900637
Subject(s) - swainsonine , chemistry , indolizidine , pyrrolizidine , bicyclic molecule , stereochemistry , nitrone , hydroboration , combinatorial chemistry , organic chemistry , alkaloid , catalysis , cycloaddition
A divergent and concise route to synthesize bicyclic iminosugars, especially polyhydroxylated pyrrolizidine and indolizidine‐based molecules, was described. Six natural product‐like bicyclic alkaloids including (−‐Swainsonine were conveniently prepared through this straightforward method. The key steps are diastereoselective allylation, ring size manipulation through hydroboration‐oxidation strategy and systematic installation of the amino functionality at the C8 position using nitrone chemistry. These Swainsonine analogues were applied for inhibition study against both α ‐hLM and α ‐hGMII. Interestingly, the C8 hydroxyl group with proper orientation plays a crucial role for inhibitory activities. The compounds possessing the C8 amino group drastically decrease their inhibitory activities.