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The Total Synthesis and Biological Properties of the Cytotoxic Macrolide FD‐891 and Its Non‐Natural ( Z )‐C12 Isomer
Author(s) -
GarcíaFortanet Jorge,
Murga Juan,
Carda Miguel,
Marco J. Alberto,
Matesanz Ruth,
Díaz J. Fernando,
Barasoain Isabel
Publication year - 2007
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.200700342
Subject(s) - cytotoxicity , aldol reaction , stereochemistry , total synthesis , chemistry , clearance , stereoselectivity , ring (chemistry) , cytotoxic t cell , tubulin , stereoisomerism , molecule , combinatorial chemistry , organic chemistry , biology , biochemistry , in vitro , medicine , microtubule , urology , microbiology and biotechnology , catalysis
A total, stereoselective synthesis of the naturally occurring, cytotoxic macrolide FD‐891 and of its non‐natural ( Z )‐C12 isomer is described. Three fragments of the main carbon chain were stereoselectively prepared by using asymmetric aldol and allylation reactions as the key steps. The molecule was then assembled by using two Julia–Kocienski olefinations to connect the three fragments and a Yamaguchi reaction to close the macrolactone ring. Some specific biological properties (cytotoxicity, binding to tubulin) have been determined for both macrolides. The E configuration of the C12–C13 olefinic bond seems to be an important feature in determining the cytotoxicity but the precise biological mechanism of the latter still remains to be cleared.