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Preface General Aspects: Epothilon History - Natural Epothilones Biosynthesis and Heterologous Products of Epothilones: Introduction - Feeding Studies and the Discovery of Natural Epothilone Variants - Identification of the Epothilone Biosynthesis Gene Cluster - Studies in vitro of the Biochemistry of Epothilon Assembly - Heterologous Expression and Genetic Engineering of the Epothilone Biosynthesis Gene Cluster - Nutrient Regulation in S. cellulosus and M. Xanthus - Conclusions Total Synthesis of the Naturally Occurring Epothilones A-F: Introduction - Synthesis Approaches to both the Epothilones A/C- and B/D Series - Syntheses of Epothilone A/C (1a, 2a) - Synthesis of Epothilones B/D (1b, 2b) - Synthesis of Fragments - Semisynthetic Degradation/Reconstruction of 2b - Syntheses of Epothilones E and F (1c, 1d) and their 12, 13-Deoxyderivatives (2c, 2d) - Nicolaou's Synthesis of Epothilone Analogues - Conclusions Semisynthetic Derivatives of Epothilones: Introduction - Modification of the O16-C8 Sector (Polyketide Sector) - Modification of the Epoxide Moiety - Side Chain Modification - Removal/Incorporation of the C13-C16 Segment - Conclusion Applications: Preclinical Pharmaceutical and Structure-Activity Relationships of Epothilones - Clinical Studies with Epothilones References
edited by Johann H. Mulzer
Epothilones have received unusual attention over the past ten years. They are novel antitumor drugs which very much like their predecessor paclitaxel (Taxol) act via microtubule stabilization. In comparison to paclitaxel and a number of alternative drugs with a similar mode of bioaction (e.g. laulimalide, eleutherobin, peluroside, discodermolide) the epothilones have significant advantages, above all very high activity in the nanomolar range and low susceptibility towards multidrug resistance. Epothilone B and several derivatives thereof are in phase I-III clinical trials; one of them (ixabepilone, BMS) is already on the market, others are supposed to appear on the market in the near future. All naturally occurring epothilones have been isolated from Sorangium cellulosum; their antitumor action is traced back to the stabilization of microtubules. In consequence, the formation of the mitototic spindle is prohibited and the cell undergoes apoptosis.
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'The Epothilones: An Outstanding Family of Anti-Tumor Agents' by Johann H. Mulzer is a digital PDF ebook for direct download to PC, Mac, Notebook, Tablet, iPad, iPhone, Smartphone, eReader - but not for Kindle. A DRM capable reader equipment is required.

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