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A Local‐Desymmetrization‐Based Divergent Synthesis of Quinine and Quinidine
Author(s) -
Lee Jaehoo,
Chen David Y.K.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201811530
Subject(s) - quinidine , quinine , quinuclidine , desymmetrization , chemistry , stereochemistry , combinatorial chemistry , organic chemistry , pharmacology , enantioselective synthesis , biology , malaria , catalysis , immunology
Herein we report a novel synthetic entry to the legendary quinuclidine natural products quinine and quinidine. The developed strategy is based on the use of a symmetrical and nonstereogenic precursor to access quinine and quinidine through a “local‐desymmetrization” approach, in stark contrast conceptually to the preparation of stereodefined disubstituted piperidines (or their acyclic precursors) as featured in all past syntheses. The developed strategy also provided quinine and quinidine derivatives that could not be readily obtained through previous total syntheses or by modification of the naturally occurring substances.