The Epothilones: An Outstanding Family of Anti-Tumor Agents: From Soil to the Clinic

PrefaceGeneral Aspects: Epothilon History - Natural EpothilonesBiosynthesis 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 - ConclusionsTotal 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 - ConclusionsSemisynthetic 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 - ConclusionApplications: Preclinical Pharmaceutical and Structure-Activity Relationships of Epothilones - Clinical Studies with EpothilonesReferences