N-Oxidation of Epothilone A-C and O-Acyl Rearrangement to C-19- and C-21-Substituted Epothilones

Gerhard Höfle; Nicole Glaser; Michael Kiffe; Hans-Jürgen Hecht; Florenz Sasse; Hans Reichenbach

doi:10.1002/(SICI)1521-3773(19990712)38:13/14<1971::AID-ANIE1971>3.0.CO;2-X

N-Oxidation of Epothilone A-C and O-Acyl Rearrangement to C-19- and C-21-Substituted Epothilones

Angew Chem Int Ed Engl. 1999 Jul 12;38(13-14):1971-1974. doi: 10.1002/(SICI)1521-3773(19990712)38:13/14<1971::AID-ANIE1971>3.0.CO;2-X.

Authors

Gerhard Höfle¹, Nicole Glaser¹, Michael Kiffe^{1

2}, Hans-Jürgen Hecht³, Florenz Sasse⁴, Hans Reichenbach⁴

Affiliations

¹ Abteilung Naturstoffchemie, Gesellschaft für Biotechnologische Forschung, Mascheroder Weg 1, D-38124 Braunschweig (Germany), Fax: (+49) 531-6181-461.
² [+] New address: Novartis Crop Protection AG, CH-4002 Basel (Switzerland).
³ Abteilung Strukturforschung, Gesellschaft für Biotechnologische Forschung Braunschweig (Germany).
⁴ Abteilung Naturstoffbiologie, Gesellschaft für Biotechnologische Forschung Braunschweig (Germany).

Abstract

A bothersome side reaction in the last step of a total synthesis of epothilone led to the formation of the thiazol-N-oxide 1. Obtained from epothilones prepared by fermentation, these biologically active N-oxides allow the extremely short synthesis of the highly active epothilones 2 with modified side chains by an O-acyl rearrangement.

Keywords: Antitumor agents; Macrocycles; Mycobacteria; Natural products; Structure–activity relationships.