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: 7162101
• 负责人: WILLIAM M SEGANISH
• 金额: $ 4.6万
• 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/7162101
• 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

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（由申请人提供）：几种天然产物目前用于治疗癌症，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，细胞对这些治疗的耐药性已经开始出现。Laulimalide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的治疗药物。因此，一条能够获得大量laulimalide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实验室的研究开发了几种催化不对称方法，将用于合成laulimalide大环化合物。此外，laulimalide的全合成将促进几个新的协议，将有广泛的合成应用的发展。特别是，一种新的杂Diels-Alder催化剂将被开发用于未活化的醛与简单二烯的反应。该研究将促进高效和原子经济的laulimalide合成，同时为化学家提供新的合成工具，用于组装其他生物重要分子。