Total Synthesis of the Antitumor Macrolide Laulimalide

目前有几种天然产品用于治疗癌症，其中最重要的是 紫杉醇。然而，这种药物和其他药物并不是对所有类型的癌症和细胞癌都有效 对这些治疗方法的抗药性已经开始显现。洛利马利是一种海洋大环内酯类化合物，具有很强的药效 具有抗癌活性，有可能发展成为一种新的有效治疗方法。因此，a 将允许获得大量劳利马利及其衍生物的合成路线将被证明是 这是药物开发的宝贵财富。特罗斯特实验室的研究已经开发出几种催化剂 将应用于合成劳利马利特大环的不对称方法学。此外， 劳利马利特的全合成将有助于开发几个具有广泛应用前景的新方案 合成应用程序。特别是，一种新的杂化Diels-Alder催化剂将被开发用于 含有单二烯的未活化的醛。拟议的研究将促进一个有效的和原子的 经济地合成劳利胺，同时为化学家提供新的合成工具 用于组装其他具有生物重要性的分子。

Several natural products are currently used for the treatment of cancer, the most important of which is paclitaxol. However, this, and other drugs are not effective against all types of cancer, and cellular resistance to these treatments has begun to emerge. Laulimalide is a marine macrolide that displays potent anti-cancer activity and has the potential to develop into a new and effective treatment. Therefore, a synthetic route that would allow access to large quantities of laulimalide and its derivitives would prove to be a valuable asset to drug development. Research in the Trost laboratories has developed several catalytic asymmetric methodologies that will be applied to the synthesis of the laulimalide macrocycle. In addition, the total synthesis of laulimalide will facilitate the development of several new protocols that will have broad synthetic applications. In particular, a new hetero Diels-Alder catalyst will be developed for the reaction of unactivated aldehydes with simple dienes. The proposed reseach will facilitate an efficient and atom economical synthesis of laulimalide, while at the same time, provide new synthetic tools for the chemist to use in the assembly of other biologically important molecules.