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Synthesis of Optically Pure Norcantharidin Analogue NCA‐01, a Highly Selective Protein Phosphatase 2B Inhibitor, and its Derivatives
Author(s) -
Shimizu Tadashi,
Iizuka Masato,
Matsukura Hiroko,
Hashizume Daisuke,
Sodeoka Mikiko
Publication year - 2012
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201200077
Subject(s) - enantiomer , chemistry , jurkat cells , phosphatase , stereochemistry , optically active , enantiomeric excess , combinatorial chemistry , organic chemistry , enzyme , enantioselective synthesis , catalysis , immune system , t cell , immunology , biology
An efficient synthetic route to optically pure norcantharidin analogue NCA‐01, a highly selective inhibitor of protein phosphatase 2B (PP2B; calcineurin), has been developed. The absolute stereochemistry of the enantiomers was determined by X‐ray crystallographic analysis. Optically pure NCA derivatives that had various substituents at the C1 position were synthesized in a similar manner. The PP2B‐inhibitory activities of NCA‐01 and its derivatives were independent of the enantiomeric form. NCA‐01 dimethyl ester potently inhibited IL‐2 production in Jurkat cells.