The Total Synthesis of (-)-Fijianolide D

(-)-斐济内酯D的全合成

• 批准号: 7837593
• 负责人: Kami Lee Hull
• 金额: $ 4.76万
• 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/7837593
• 关键词: Aldehydes; Alder plant; Alkylation; Biological; Biological Factors; Complex; Development; Goals; 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; public health relevance; 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）：拟议研究的具体目的是开发一种有效的，收敛的，不对称的细胞毒性天然产物fijanolide D的全合成，该产物已显示出有希望的生物活性，合成材料的生产将允许进一步测试其抗癌活性。有机金属化学家已经开发了许多强大的方法立体，区域，和化学选择性形成复杂的有机分子。在拟议的合成中使用的合成策略既利用了成熟的方法，也利用了相对较新的方法；此外，它作为一个支架，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。它特别强调了一个钌催化的醛烯反应区域选择性大环化。公共卫生相关性：许多具有生物活性的天然产品只能从自然界获得非常少量的产品；例如，从一公斤多的海绵中只分离出6毫克的斐济内酯D。合成材料的生产允许对生物活性进行额外的筛选，一旦合成路线确定，就可以制作类似物用于结构-活性关系（SAR）研究。这一过程极大地有助于发现新的药物制剂。