The Total Synthesis of (-)-Fijianolide D

(-)-斐济内酯D的全合成

• 批准号: 8067071
• 负责人: Kami Lee Hull
• 金额: $ 5.13万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8067071
• 关键词: Aldehydes; Alder plant; Alkylation; Biological; Biological Factors; Complex; Development; Goals; Health; Kilogram; Macrolides; Methodology; Methods; Nature; Pharmacologic Substance; Porifera; Process; Production; Reaction; Research; Route; Screening procedure; Sea; Structure-Activity Relationship; Testing; Transition Elements; Zinc; analog; anticancer activity; catalyst; cytotoxic; rapid technique; scaffold; tetrahydrofuran

DESCRIPTION (provided by applicant): The specific aim of the proposed research is to develop an efficient, convergent, asymmetric total synthesis of the cytotoxic natural product fijianolide D, which has shown promising biological activity, and the production of synthetic material will allow for further testing of its anticancer activities. Organometallic chemists have developed many powerful methodologies for the stereo, regio, and chemeoselective formation of complex organic molecules. The synthetic strategy use in the proposed synthesis of fijianolide D utilizes both well established and relatively new methodologies; additionally, it as a scaffold to showcase the versatility of several transition-metal catalyzed methods for the rapid assembly of this complex 20-membered macrolide. It especially highlights the a Ru-catalyzed Alder-ene reaction for regioselective macrocyclization. PUBLIC HEALTH RELEVANCE: Many biologically active natural products are only available from nature in very small amounts; for example, only 6 mg of fijianolide D was isolated from over a kilogram of sea sponges. The production of synthetic material allows for additional screening of biological activity and once a synthetic route is established, analogs can be made for structure-activity relationship (SAR) studies. This process aids greatly in the discovery of new pharmaceutical agents.

描述（由申请人提供）：拟定研究的具体目的是开发细胞毒性天然产物fijiantine D的高效、收敛、不对称全合成，该天然产物已显示出有前途的生物活性，合成材料的生产将允许进一步测试其抗癌活性。有机化学家已经开发了许多强大的立体，区域和化学选择性形成复杂的有机分子的方法。在所提出的fijiantenD合成中使用的合成策略利用了成熟的和相对较新的方法;此外，它作为支架展示了几种过渡金属催化方法的多功能性，用于快速组装这种复杂的20元大环内酯。它特别强调了钌催化的Alder烯反应的区域选择性大环化。公共卫生关系：许多具有生物活性的天然产物只能从自然界中以非常少量的形式获得;例如，从超过1公斤的海绵中仅分离出6毫克的斐济维生素D。合成材料的生产允许对生物活性进行额外的筛选，并且一旦建立了合成路线，就可以制备类似物用于结构-活性关系（SAR）研究。这一过程大大有助于发现新的药物制剂。