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Conception, Synthesis, and Biological Evaluation of Original Discodermolide Analogues
Author(s) -
de Lemos Elsa,
Agouridas Evangelos,
Sorin Geoffroy,
Guerreiro Antonio,
Commerçon Alain,
Pancrazi Ange,
Betzer JeanFrançois,
Lannou MarieIsabelle,
Ardisson Janick
Publication year - 2011
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.201100675
Subject(s) - total synthesis , moiety , stereochemistry , chemistry , combinatorial chemistry
Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive “U” shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal ( Z )‐diene moiety, of the methyl group at the C14‐position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.