Synthetic and structure-activity relationship study on a new anticancer agent, yaku'amide A

从海绵中分离出一种细胞毒肽yaku'amide A，它具有极强的细胞毒性。雅库酰胺A对一组39种人类癌细胞系的生长抑制活性在已知的抗癌药物中是非常独特的。因此，亚枯酰胺A具有发挥其生物活性的新的作用方式。本项目开发了一种新的利用铜介导的交叉偶联反应组装脱氢氨基酸残基的方法，并首次实现了亚库酰胺A的全合成。此外，还建立了利用Staudinger连接法合成Z-脱氢氨基酸的另一种方法。

A cytotoxic peptide yaku'amide A was isolated from a marine sponge as an extremely potent cytotoxin. The growth-inhibitory activity of yaku'amide A against a panel of 39 human cancer cell lines is quite unique among known anticancer drugs. Therefore, it is suggested that yaku'amide A possesses new mode of action to exert its bioactivity. In order to evaluate its detailed biological activity, chemical synthesis for supplying material was required.In this project, the development of a new assembly method of the dehydroamino acid residue utilizing Cu-mediated cross coupling reaction and the first total synthesis of yaku'amide A were achieved. In addition to this, another approach for the synthesis of Z-dehydroamino acid using Staudinger ligation was also established.