Total Synthesis of the Antitumor Macrolide Laulimalide

描述（由申请人提供）：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都有效，而且对这些治疗的细胞耐药性已经开始出现。Laulimalide是一种海洋大环内酯类药物，具有很强的抗癌活性，有可能发展成为一种新的有效的治疗方法。因此，一种能够获得大量月桂酰胺及其衍生物的合成途径将被证明是药物开发的宝贵资产。Trost实验室的研究已经开发了几种催化不对称方法，将应用于月桂烷酰胺大环的合成。此外，月桂酰胺的全合成将促进几种具有广泛合成应用的新方案的发展。特别地，将开发一种新的杂化Diels-Alder催化剂，用于非活化醛与简单二烯的反应。本研究将促进laulimalide的高效和原子经济合成，同时为化学家用于其他重要生物分子的组装提供新的合成工具。

DESCRIPTION (provided by applicant): 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 derivatives 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 research 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.