Studies for Structure-Activities Relationships of Reveromycin A : An Inhibitor of Eukaryotic Cell Growth

Reveromycin A是一种由链霉菌产生的新型聚酮型抗生素，可抑制小鼠表皮角质形成细胞中表皮生长因子诱导的有丝分裂活性。reveromycin A的特征性结构特征包括1,7- dioxspiro[5.5]十一烷部分，即6,6-螺缩醛体系含有半琥珀酸、两个烯基羧酸以及甲基和正丁基。制备了各种类型的左旋霉素A衍生物，并测定了它们对异酰基trna合成酶活性和体外蛋白合成的抑制作用，以及对src^<ts> NRK细胞形态逆转的活性。结果表明，C5羟基和C24羧基对这些活性尤为重要。

Reveromycin A is a novel polyketide-type antibiotic produced by Streptomyces sp. and inhibits mitogenic activity induced by the epidermal 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-spiroacetal system bearing a hemisuccinate, two alkenyl carboxylic acids, and methyl and n-butyl groups. Various derivatives of reveromycin A were prepared and their inhibitory effects on both isoleucyl-tRNA synthetase activity and in vitro protein synthesis, and activities on the morphological reversion of src^<ts> NRK cells were assayed. It was clarified that the C5 hydroxyl group and C24 carboxyl group were particularly important for these activities.