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The Synthesis of trans ‐Flavan‐3‐ol Gallates by Regioselective Oxidative Etherification and Their Cytotoxicity Mediated by 67 LR
Author(s) -
Shiraishi Nana,
Kumazoe Motofumi,
Fuse Shinichiro,
Tachibana Hirofumi,
Tanaka Hiroshi
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201602817
Subject(s) - regioselectivity , epichlorohydrin , chemistry , epoxide , phenols , enantiomer , flavan , organic chemistry , stereochemistry , medicinal chemistry , catalysis
We report on a chiral pool approach for the synthesis of trans ‐flavan‐3‐ol gallates from epichlorohydrin. The trans ‐flavan‐3‐ol gallates were prepared by the cycloetherification of the phenol at the C2 benzylic position of 2‐acylozyl‐1,3‐diarylpropane during regioselective C−H oxidation. The 1,3‐diarylpropanes were prepared starting from epichlorohydrin by epoxide opening with A and B ring precursors, followed by acylation of the resultant alcohol with galloyl chloride. The availability of both the enantiomers of epichlorohydrin allowed the preparation of the corresponding enantiomer using the same procedure. The cytotoxicity of the compounds against U266 cells was tested, in which 5‐deoxy‐7,3′‐ O ‐dimethyl gallocatechin gallate exhibited cytotoxicity that was more than ten times stronger than natural (−)‐EGCG. In addition, the absolute configuration of the derivatives did not critically affect the biological activity.