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.
Natural products with taxol-like anti-tumour activity : synthetic approaches to eleutherobin and dictyostatin / C. Gennari, D. Castoldi, O. Sharon. - In: PURE AND APPLIED CHEMISTRY. - ISSN 0033-4545. - 79:2(2007), pp. 173-180. [10.1351/pac200779020173]
Natural products with taxol-like anti-tumour activity : synthetic approaches to eleutherobin and dictyostatin
C. GennariPrimo
;
2007
Abstract
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.Pubblicazioni consigliate
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