Abstract：
:Epothilones A and B, two compounds that have been recently isolated from myxobacterium Sorangium cellulosum strain 90, have generated intense interest among chemists, biologists and clinicians owing to the structural complexity, unusual mechanism of interaction with microtubules and anticancer potential of these molecules. Like taxol, they exhibit cytotoxicity against tumour cells by inducing microtubule assembly and stabilization, even in taxol-resistant cell lines. Following the structural elucidation of these molecules by X-ray crystallography in 1996, several syntheses of epothilones A and B have been reported, indicative of the potential importance of these molecules in the cancer field. Here we report the first solid-phase synthesis of epothilone A, the total synthesis of epothilone B, and the generation of a small epothilone library. The solid-phase synthesis applied here to epothilone A could open up new possibilities in natural-product synthesis and, together with solution-phase synthesis of other epothilones, paves the way for the generation of large combinatorial libraries of these important molecules for biological screening.
journal_name
Naturejournal_title
Natureauthors
Nicolaou KC,Winssinger N,Pastor J,Ninkovic S,Sarabia F,He Y,Vourloumis D,Yang Z,Li T,Giannakakou P,Hamel Edoi
10.1038/387268a0subject
Has Abstractpub_date
1997-05-15 00:00:00pages
268-72issue
6630eissn
0028-0836issn
1476-4687journal_volume
387pub_type
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