Synthetic Studies of Reveromycin A : An Inhibitor of Eukaryotic Cell Growth

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Reveromybin A is a novel polyketide-type antibiotic produced by Steptomyces sp. and inhibits mitogenic activity induced by the epidennal growth factor in a mouse epidermal keratinocyte. The characteristic structural features of reveromycin A include a 1, 7-dioxaspiro[5.5]undecane moiety, that is, the 6, 6-splroacetal system bearing a hemisuccinate, two alkenyl carboxylic acids, and methyl and n.-butyl groups. The first total synthesis of reveromycin A has been designed and accomplished. Our synthesis is based on the stereoselective and convergent synthesis of the 6, 6-spiroacetal system followed by the succinylation of tertiary alcohol under high pressure and the installation of the polyene-containing side chains. We also studied the syntheses and activities of reveromycin A derivatives.