Structure-activity relationship study of hatermalides by using medicinal chemistry

巨环内酯和双内酯是从冲绳海洋动物中分离出来的具有细胞毒性的巨环内酯类物质。有趣的是，草甘膦NA对卤虾的毒性较强，而草甘膦NA甲酯和双卤乙酯A的毒性较弱。我计划合成haterumalide衍生物并评价其生物活性。结果表明，黄顶草具有较强的细胞毒性，其中的氯烯烃部分是必不可少的。同时，我也完成了双体E核心碳骨架的合成。

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.