Total Synthesis of 26-Fluoro-epothilone B

Guido Koch; Olivier Loiseleur; Karl-Heinz Altmann

doi:10.1055/s-2004-817771

LETTER

Total Synthesis of 26-Fluoro-epothilone B

Guido Koch*^a, Olivier Loiseleur^b, Karl-Heinz Altmann^c
^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

Abstract

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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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References

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