Total synthesis of (−)-dictyostatin, a microtubule-stabilising anticancer macrolide of marine sponge origin |
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Authors: | Ian Paterson Robert Britton Oscar Delgado Nicola M. Gardner Arndt Meyer Guy J. Naylor Karine G. Poullennec |
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Affiliation: | University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK |
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Abstract: | An efficient convergent synthesis of the anticancer marine macrolide (−)-dictyostatin is described that proceeds in 4.6% yield over 27 steps. Most of the stereocentres were configured using substrate control, making use of a common building block to install the C12-C14 and C20-C22 stereotriads, with a lactate boron aldol reaction employed to construct a C4-C10 β-ketophosphonate as utilised in the pivotal Still-Gennari HWE coupling step with a fully elaborated C11-C26 aldehyde. Following introduction of the (2Z,4E)-dienoate, a modified Yamaguchi macrolactonisation and deprotection delivered the requisite 22-membered macrocyclic lactone. |
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Keywords: | Macrolide Cytotoxic Tubulin Aldol reaction Olefination |
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