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Total Synthesis of Oxazole‐ and Cyclopropane‐Containing Epothilone B Analogues by the Macrolactonization Approach
Author(s) -
Nicolaou K. C.,
Sarabia Francisco,
Finlay M. Ray V.,
Ninkovic Sacha,
King N. Paul,
Vourloumis Dionisios,
He Yun
Publication year - 1997
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.19970031212
Subject(s) - oxazole , stereochemistry , epothilone , aldol reaction , moiety , chemistry , thiazole , total synthesis , cyclopropane , wittig reaction , ring (chemistry) , organic chemistry , catalysis
In order to probe structure‐activity relationships in the epothilone area, two series of epothilone B analogues have been designed and synthesized. The first series containing an oxazole moiety in place of a thiazole on the side chain was constructed by utilizing key intermediates 7–9 or 10, 12 , and 13 (Scheme 1), whereas the second series containing an ethano group instead of the gem ‐dimethyl group at position 4 was synthesized from fragments 42 and 43 . A Yamaguchi‐type macrolactonization reaction was used to construct the macrocycle from a secoacid, which was assembled, in both cases, by means of a) an aldol reaction, b) an Enders alkylation, and c) a Wittig‐type reaction. This convergent strategy provided access to oxazole analogues 2,4,29–32 and 4,4‐ethano derivatives 3,40,60–63 for biological studies.