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: 7524408
• 负责人: WILLIAM M SEGANISH
• 金额: $ 2.07万
• 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 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7524408
• 关键词: Acids; Aldehydes; Alder plant; Alkenes; Alkynes; Biological Factors; Coupling; Cyclization; Development; Diels Alder reaction; Laboratories; Macrolides; Malignant Neoplasms; Marines; Methodology; Pharmaceutical Preparations; Procedures; Protocols documentation; Reaction; Research; Resistance; Route; Ruthenium; Scheme; Time; cancer therapy; cancer type; catalyst; diene; drug development; laulimalide; novel; oxidation; tool

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.

目前有几种天然产物用于治疗癌症，其中最重要的是 紫杉醇。然而，这种药物和其他药物并不能有效对抗所有类型的癌症，并且细胞 对这些治疗的耐药性已经开始出现。 Laulimalide 是一种海洋大环内酯，具有强效作用 抗癌活性，并有可能发展成为一种新的有效治疗方法。因此，一个 事实证明，能够获得大量月桂马内酯及其衍生物的合成路线 药物开发的宝贵资产。 Trost 实验室的研究已开发出多种催化 将应用于月桂马内酯大环化合物合成的不对称方法。此外， 月桂马内酯的全合成将促进几个新方案的开发，这些新方案将具有广泛的应用前景 合成应用。特别是，将开发一种新的异质狄尔斯-阿尔德催化剂，用于以下反应： 未活化的醛与简单的二烯。拟议的研究将促进高效和原子 经济地合成月桂马内酯，同时为化学家提供新的合成工具 用于组装其他重要的生物学分子。