The Total Synthesis of (-)-Fijianolide D

描述(申请人提供)：拟议研究的具体目标是开发一种高效、收敛、不对称的细胞毒性天然产物Fijianolide D的全合成，该产品已显示出良好的生物活性，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来形成复杂的有机分子的立体、区域和化学选择性形成。在建议的合成中使用的合成策略使用了成熟的和相对较新的方法；此外，它还作为一个支架，展示了几种过渡金属催化的方法的多功能性，以快速组装这种复杂的20元大环内酯。特别强调了区域选择性大环化反应中Ru催化的Alder-ene反应。与公共健康相关：许多具有生物活性的天然产品只能从自然界获得极少量的产品；例如，从超过1公斤的海绵中只分离出6毫克的菲甲内酯D。合成材料的生产允许对生物活性进行额外的筛选，一旦建立了合成路线，就可以进行类似的结构-活性关系(SAR)研究。这一过程极大地有助于发现新的药剂。

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.