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Stereoselective Synthesis of the Halaven C14–C26 Fragment from D ‐Quinic Acid: Crystallization‐Induced Diastereoselective Transformation of an α‐Methyl Nitrile
Author(s) -
Belanger Francis,
Chase Charles E.,
Endo Atsushi,
Fang Francis G.,
Li Jing,
Mathieu Steven R.,
Wilcoxen Annie Z.,
Zhang Huiming
Publication year - 2015
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.201501143
Subject(s) - quinic acid , stereocenter , nitrile , stereoselectivity , chemistry , stereochemistry , substrate (aquarium) , crystallization , derivative (finance) , transformation (genetics) , combinatorial chemistry , organic chemistry , enantioselective synthesis , biochemistry , catalysis , biology , ecology , gene , financial economics , economics
Crystallization‐induced diastereoselective transformation (CIDT) of an α‐methyl nitrile completes an entirely non‐chromatographic synthesis of the halichondrin B C14–C26 stereochemical array. The requisite α‐methyl nitrile substrate is derived from D ‐quinic acid through a series of substrate‐controlled stereoselective reactions via a number of crystalline intermediates that benefit from a rigid polycyclic template. Therefore, all four stereogenic centers in the Halaven C14–C26 fragment were derived from the single chiral source D ‐quinic acid.