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Synlett 2004(4): 693-697  
DOI: 10.1055/s-2004-817771
LETTER
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of 26-Fluoro-epothilone B

Guido Koch*a, Olivier Loiseleurb, Karl-Heinz Altmannc
a Novartis Institutes for Biomedical Research, WSJ-507.704, 4002 Basel, Switzerland
Fax: +41(61)32442 38; e-Mail: guido.koch@pharma.novartis.com;
b Syngenta AG, WRO-1060.5.04, 4002 Basel, Switzerland
c ETH Zürich, Department of Chemistry and Applied BioSciences, Institute of Pharmaceutical Sciences, Winterthurerstr.190, 8057 Zürich, Switzerland
Further Information

Publication History

Received 4 December 2003
Publication Date:
10 February 2004 (online)

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Abstract

An efficient synthesis of the epothilone B derivative 26-fluoroepothilone B (1) was realized by early introduction of the synthetically demanding fluoromethyl epoxide function. The presence of a fluoro substituent results in a remarkable increase in the stability of the epoxide, which tolerates the wide range of reaction conditions required for the fragment coupling step and end game transformations.

Key words

epothilone - total synthesis - fluorine - epoxides - sub­stituent effects

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