N-oxidation of epothilone A-C and O-acyl rearrangement to C-19- and C- 21-substituted epothilones

Angewandte Chemie - International Edition

Volumn 38, Issue 13-14, 1999, Pages 1971-1974

  Höfle, Gerhard ^a   Glaser, Nicole ^a   Kiffe, Michael ^a,b   Hecht, Hans Jürgen ^a   Sasse, Florenz ^a   Reichenbach, Hans ^a  

^a HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Antitumor agents; Macrocycles; Mycobacteria; Natural products; Structure activity relationships

Indexed keywords

ANTINEOPLASTIC AGENT; DEOXYEPOTHILONE B; EPOTHILONE A; EPOTHILONE B; EPOTHILONE C; NATURAL PRODUCT; TAXOL; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIFUNGAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CHEMICAL MODIFICATION; CYTOTOXICITY; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MOUSE; MYCOBACTERIUM; NONHUMAN;

EID: 0343486338     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/(sici)1521-3773(19990712)38:13/14<1971::aid-anie1971>3.0.co;2-x     Document Type: Article

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29. The use of 1.5 equivalents of m-chloroperbenzoic acid in chloroform for 8 d at -20°C leads to a conversion of 40 and 90%, respectively. Based on the amount of 1c and 1d consumed, 40% of 1a and 70% of 1b are obtained.
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31. -3 Programs used: SIR92 (Giacovazzo, 1994) and Siemens-SHELXL-PLUS (Unix version). Crystallographic data (excluding structure factors) of the structure described in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-116610. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (+44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
32. An S-oxide proposed in a report of a total synthesis of epothilone A (K. C. Nicolaou, Y. He, D. Vourloumis, H. Vallberg, F. Roschanger, F. Sarabia, S. Ninkovic, Z. Yang, J. I. Frujillo, J. Am. Chem. Soc. 1997, 119, 7960-7973) was presumably the N-oxide 2a.
33. 2 and 3-H for 2 as well as for 1 are in a trans and gauche orientation, respectively.
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37. Also without precedent is the isomeric structure of the N-acetyl-S-oxide II. For structural proof, the reaction is to be applied to model compounds to possibly obtain crystalline compounds of type II or III.
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