Oxidative and reductive transformations of epothilone A

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 21, 1998, Pages 3025-3030

  Sefkow, Michael ^a,b   Kiffe, Michael ^a,c   Schummer, Dietmar ^a,d   Höfle, Gerhard ^a  

^a HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^b UNIVERSITY OF POTSDAM   (Germany)

^c NOVARTIS PHARMA AG   (Switzerland)

^d SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

EPOTHILONE A; NATURAL PRODUCT;

ARTICLE; DERIVATIZATION; DRUG CYTOTOXICITY; DRUG OXIDATION; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TRANSFORMATION; OXIDATION REDUCTION REACTION;

ANTINEOPLASTIC AGENTS; EPOTHILONES; EPOXY COMPOUNDS; FERMENTATION; OXIDATION-REDUCTION; THIAZOLES;

EID: 0032212669     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00545-9     Document Type: Article

References (46)

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26. 10. The preference for the C7 hydroxy group was also observed with chlorohydrin 22. Despite an additional hydroxy group at C13, only C7 reacted with PDC to give hemiacetal 23 as the sole product (60%). (matrix presented)
27. 1H NMR spectrum of hemiacetal 2 revealed, that it centaines approximately 5% of the bis-keto form.
28. 12. The tri-oxo derivative 4 might be a result of initial C3-oxidation to compound 3, which cannot close to an acetal and, thus, allowing oxidation of the remaining hydroxy group.
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31. 3 the C12-C13 bromohydrin (3:1 mixture of regioisomers) was isolated in 45% yield caused by the formation of HBr during the reaction although no electrophilic substitution products could be detected. Using powdered sodium bicarbonate as buffer the C19-bromo analog of 1a was obtained in 40% yield through an electrophilic bromination of thiazole moiety.
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35. 18. The major product of these reactions, which was isolated in up to 50% yield is an epothilone analog bearing an oxygen at the thiazole nitrogen, see, for similar examples, reference 4b.
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45. 27. The advantage of this procedure are the non-basic conditions in an attempt to avoid possible basic decomposition of the substrate. For a discussion, see: Horikawa, Y.; Watanabe, M.; Fujiwara, T.; Takeda, T.; J. Am. Chem. Soc. 1997, 119, 1127-1128.
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