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

从海绵中分离出一种极有效的细胞毒肽yaku'amide A。在已知的抗癌药物中，雅库酰胺A对39种人类癌细胞系的生长抑制活性是非常独特的。因此，提示雅库酰胺A具有新的作用方式来发挥其生物活性。为了评价其详细的生物活性，需要化学合成提供材料。本项目利用cu介导的交叉偶联反应，开发了脱氢氨基酸残基的组装新方法，并首次实现了雅库酰胺a的全合成。除此之外，还建立了另一种利用Staudinger连接法合成z -脱氢氨基酸的方法。

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.