Eleutherobin and dictyostatin are antimitotic compounds which exert their cytotoxic activity by a taxol-like mode of action, i.e., hypernucleating tubulin assembly and interfering with the dynamic instability of the cytoskeleton during mitosis. A formal total synthesis of eleutherobin was accomplished by accessing a key intermediate reported by Danishefsky and coworkers in their 1998 synthesis of the natural product. The key step of our strategy, used for obtaining the [8.4.0] fused bicyclic ring system, is a ring-closing metathesis (RCM) reaction of a densely functionalized diene under forcing conditions, using Grubbs’ second-generation catalyst. Synthetic approaches to dictyostatin are also described, and in particular the preparation of the C15–C23 fragment of the macrolide, containing 5 of its 11 stereocenters.
|Titolo:||Natural products with taxol-like anti-tumour activity : synthetic approaches to eleutherobin and dictyostatin|
|Autori interni:||GENNARI, CESARE MARIO ARTURO (Primo)|
|Parole Chiave:||Antitumor agents; Microtubule-stabilizing agents; Natural products; Ring-closing metathesis; Stereocontrol; Total synthesis|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||2007|
|Digital Object Identifier (DOI):||10.1351/pac200779020173|
|Appare nelle tipologie:||01 - Articolo su periodico|