Structure-activity relationship study of hatermalides by using medicinal chemistry

哈特鲁内酯和双内酯是从冲绳海洋动物中分离出来的细胞毒性大环内酯类化合物。值得注意的是，鱼腥草素NA对卤虫有较强的毒性，而鱼腥草素NA甲酯和双内酯A的毒性较小。我计划合成虎杖内酯的衍生物，并对其生物活性进行评估。因此，我阐明了杂毛虫内酯中的氯烯烃部分对于杂毛虫内酯的强烈细胞毒性是必不可少的。并实现了双内酯E。

Haterumalides and biselides are cytotoxic macrolide isolated from the Okinawan marine animals. Interestingly, haterumalide NA showed strong toxicity against brine shrimp, while haterumalide NA methyl ester and biselide A are less toxic. I planned to synthesize haterumalide derivatives and to evaluate its biological activity. As a result, I elucidated that chloroolefin part of haterumalides is essential for the strong cytotoxicity of haterumalides. Also, I have achieved the synthesis of core carbon framework of biselide E.