Total Syntheses of Epothilones B and D

Total Syntheses of Epothilones B and D

Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1−C6 (fragment D), C7−C10 (fragment C), and C1...

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Veröffentlicht in:Journal of organic chemistry 2000-11, Vol.65 (22), p.7456-7467
Hauptverfasser: Mulzer, Johann, Mantoulidis, Andreas, Öhler, Elisabeth
Format: Artikel
Sprache:eng
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Antineoplastic Agents, Phytogenic - chemical synthesis
Epothilones
Epoxy Compounds - chemical synthesis
Indicators and Reagents
Thiazoles - chemical synthesis
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container_title Journal of organic chemistry
container_volume 65
creator Mulzer, Johann
Mantoulidis, Andreas
Öhler, Elisabeth
description Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1−C6 (fragment D), C7−C10 (fragment C), and C11−C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.
doi_str_mv 10.1021/jo0007480
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subjects Antineoplastic Agents, Phytogenic - chemical synthesis
Epothilones
Epoxy Compounds - chemical synthesis
Indicators and Reagents
Thiazoles - chemical synthesis
title Total Syntheses of Epothilones B and D
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