Epothilones related structures

The epothilones are 16-membered lactones that have been isolated from mycobacteria. Epothilones A-D differ in the presence of the C(12)-C(13) epoxide and in the C-12 methyl group. Although the epothilones are structurally very different from Taxol, the biochemical mechanism of anticancer action is related, and epothilone A and analogs are of substantial current interest as chemotherapeutic agents.143 Schemes 13.48-13.51 summarize four syntheses of epothilone A. Syntheses of epothilone B have also been completed.144... 

Altmann KH, Wartmann M, O Reilly T. Epothilones and related structures—anew class of microtubule inhibitors with potent in vivo antitumor activity. Biochim Biophys Acta 2000 1470(3) M79-91. 

The chemistry, biology, and structure activity relationship (SAR) of epothilones have been extensively discussed in recent review articles. it is thus not the intention of this chapter to provide a detailed review of these different facets of epothilone-related research. Rather, this chapter will focus on some selected aspects of the chemistry, biology, and clinical evaluation of natural epothilones and their synthetic analogs, with particular emphasis on SAR work performed in our... 

MS As with different chemical structures have been discovered in different natural sources. Taxanes come from plants, epothilones and cyclostreptin are of microbial origin, whereas discodermolide, dictyostatin, eleutherobin, laulimalide and peloruside were discovered in sea organisms (for a classification and MSA structures see [20]). We do not know of MSAs from a purely synthetic chemistry not related to natural products. 

Structure Activity Relations and the EC Binding Model of Epothilone A. 000... 

Vinblastine (2) and several vinca-related drugs bind to a different site, as do a number of other drugs that bind competitively with each other, but do not compete with the colchicinoids. Like the colchinoids, vinca alkaloids destabilise microtubules. The Taxol (3) binding site is located in a pocket that is lined by several hydrophobic residues and is well defined from crystal structures of aP-tubulin. It represents the putative binding site for other microtubule stabilising drugs like epothilones [2,11]. 

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