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The Epothilones: An Outstanding Family of Anti-Tumor Agents pp 135–156Cite as

Semisynthetic Derivatives of Epothilones

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Abstract

Semisynthetic derivatives of natural products traditionally occupy a prominent space in natural-product-based drug discovery (1, 2). As many biologically active natural products exhibit a high degree of structural complexity (3), the chemical derivatization of material isolated from natural sources often represents the only feasible means (or at least the only economically viable approach) to explore structure-activity-relationships (SAR) and to produce analogs with more favorable pharmacokinetic and pharmacological properties than the natural product lead. Examples of clinically important drugs that are semisynthetic derivatives of natural products exist in virtually all disease areas (1, 2); in the treatment of cancer this includes compounds such as etoposide or teniposide (derived from podophyllotoxin) (4–6), irinotecan and topotecan (derived from camptothecin) (7–9), or docetaxel (derived from 10-deacetylbaccatin III) (10, 11). Even for taxol (11), which is a natural product (12), the sustained supply of sufficient quantities of material for widespread clinical use could only be secured through the development of a semisynthetic production process from another natural product, namely, 10-deacetylbaccatin III (13). In light of these facts, it is not surprising that semisynthesis approaches have also featured prominently in the elucidation of the SAR for epothilones and in the discovery of a number of clinical development candidates.

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Authors and Affiliations

  1. Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Hönggerberg. HCI H 405, ETH Zürich, Wolfgang-Pauli-Str. 10, 8093, Zürich, Switzerland

    Prof. Dr. Karl-Heinz Altmann

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  1. Prof. Dr. Karl-Heinz Altmann
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Altmann, KH. (2009). Semisynthetic Derivatives of Epothilones. In: The Epothilones: An Outstanding Family of Anti-Tumor Agents. Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products, vol 90. Springer, Vienna. https://doi.org/10.1007/978-3-211-78207-1_4

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