Total Synthesis of the Antitumor Macrolide Laulimalide

抗肿瘤大环内酯月桂马内酯的全合成

• 批准号: 7055429
• 负责人: WILLIAM M SEGANISH
• 金额: $ 4.21万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-03 至 2008-01-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055429
• 关键词: Diels Alder reaction; aldehydes; antineoplastic antibiotics; biological products; diene; drug design /synthesis /production; macrolide antibiotics; postdoctoral investigator

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.

描述(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，细胞对这些治疗方法的耐药性已经开始出现。洛利马利特是一种海洋大环内酯类化合物，具有很强的抗癌活性，有可能发展成为一种新的有效治疗方法。因此，一条能够获得大量劳利马利及其衍生物的合成路线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出几种催化不对称方法，这些方法将应用于合成劳利马利大环。此外，劳利马利德的全合成将有助于开发几个具有广泛合成应用的新协议。特别是，将开发一种新的杂化Diels-Alder催化剂，用于未活化的醛与单二烯的反应。这项研究将有助于高效和原子经济地合成劳利马胺，同时也为化学家提供了新的合成工具，用于组装其他具有生物重要性的分子。