New Asymmetric Transformations and Chemical Synthesis of Natural Products

描述（由申请人提供）：本研究项目旨在开发新的高效方法来制备复杂的生物活性有机分子。在K99指导阶段提出的研究将在Larry Overman教授的指导下进行一到两年，涉及发现新的不对称Pd（ll）催化的丙烯基三氯乙酸酯反应。在该方法发展之前，它将在有效合成微叶绿醌的背景下进行评估，这是一种对几种细胞系表现出细胞毒性的小分子。R00独立阶段（第3年至第5年）将专注于发现不对称金属介导的偶联反应，以促进全碳四级立体中心的形成，这是复杂分子合成中经常遇到的挑战。这种强大的方法将扩展到包括级联反应，用于从简单的前手性起始材料开始快速构建富含对映体的熔融和双环体系。最后，研究了两种有效抗炎化合物芒豆醇A和C的不对称全合成。

DESCRIPTION (provided by applicant): This research program aims to develop new and efficient methods for the preparation of complex bioactive organic molecules. Research proposed in the K99 Mentored phase will be carried out over one to two years with Professor Larry Overman and involve the discovery of new asymmetric Pd(ll)-catalyzed reactions of allylic trichloroacetimidates. Pending the development of this methodology, it will be evaluated in the context of an efficient synthesis of microphyllaquinone, a small molecule that exhibits cytotoxicity against several cell lines. The R00 Independent phase (years 3 to 5) will focus on the discovery of an asymmetric metal-mediated coupling reaction to promote the formation of all-carbon quaternary stereocenters, a challenge often encountered in complex molecule synthesis. This powerful methodology will be expanded to include cascade reactions for the rapid construction of enantio-enriched fused and bicyclic ring systems beginning from simple, prochiral starting materials. Finally, the asymmetric total syntheses of two potent anti-inflammatory compounds, mangicols A and C, will be pursued. If the goals of this proposal are achieved, new chemical methods for preparing biologically active molecules will be developed. Ultimately, this contribution will facilitate the discovery of new medicinal agents for treating human illnesses.