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Probing the Ring Size of Epothilones: Total Synthesis of [14]‐, [15]‐, [17]‐, and [18]Epothilones A
Author(s) -
Nicolaou K. C.,
Sarabia Francisco,
Ninkovic Sacha,
Finlay M. Ray V.,
Boddy Christopher N. C.
Publication year - 1998
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/(sici)1521-3773(19980202)37:1/2<81::aid-anie81>3.0.co;2-c
Subject(s) - epothilones , epothilone , ring size , ring (chemistry) , tubulin , chemistry , stereochemistry , microtubule , ixabepilone , biology , organic chemistry , microbiology and biotechnology , cancer , genetics , metastatic breast cancer , breast cancer
Unfamiliar rings. The pharmocophore of epothilone A does not tolerate changes in ring size. The 14‐, 15‐, 17‐, and 18‐membered ring analogues 1 ( n = 1, 2, 4, 5) of epothilone and their deoxy counterparts show only low levels of activity in tubulin polymerization assays, with the exception of [18]desoxyepothilone A. These findings underscore the high specificity of the tubulin receptor.