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Total Synthesis of Oxazole‐ and Cyclopropane‐Containing Epothilone A Analogues by the Olefin Metathesis Approach
Author(s) -
Nicolaou K. C.,
Vallberg Hans,
King N. Paul,
Roschangar Frank,
He Yun,
Vourloumis Dionisios,
Nicolaou Christopher G.
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.19970031211
Subject(s) - oxazole , chemistry , moiety , epothilones , epothilone , olefin metathesis , thiazole , salt metathesis reaction , olefin fiber , aldol reaction , stereochemistry , total synthesis , tetrahydropyran , metathesis , combinatorial chemistry , ring (chemistry) , organic chemistry , catalysis , polymerization , polymer
For structure‐activity relationship studies, two series of epothilone A ( 1 ) analogues have been designed and synthesized, one containing an oxazole moiety instead of the thiazole heterocycle and the other containing a spirocyclopropane moiety in place of the gem ‐dimethyl group at position C‐4 (4,4‐ethano‐epothilones). The olefin metathesis strategy in solution was utilized for the chemical synthesis of these compounds starting with key building blocks 7–9 for the oxazole series (compounds 2, 14–18, 21–26 ) and building blocks 8, 30 , and 31 for the 4,4‐ethano series (compounds 3,39–43, 46–51 ). The convergent strategy towards the designed epothilone A series involved a) an aldol condensation reaction, b) an esterification reaction, c) an olefin metathesis reaction catalyzed by [RuCl 2 (=CHPh)‐(PCy 3 ) 2 ], and d) epoxidation of the macrocycle double bond.