New Asymmetric Transformations and Chemical Synthesis of Natural Products

这项研究计划旨在开发新的有效方法来制备络合物 生物活性有机分子。在K99指导阶段提出的研究将在1-2年内进行 与拉里·奥弗曼教授合作多年，发现了新的不对称Pd(II)催化反应 三氯乙酸烯丙酯。在开发这一方法之前，将在 一种高效合成小叶醌的背景，它是一种具有细胞毒性的小分子化合物 几个细胞系。Roo独立阶段(3-5年)将专注于发现不对称的 金属介导的偶联反应促进全碳四元立体中心的形成 在复杂分子合成中经常遇到的挑战。这一强大的方法将扩展到 包括用于快速构建富对映体稠环和双环体系的级联反应 从简单的前手性起始材料开始。最后，两种强势化合物的不对称全合成 抗炎化合物，甘露醇A和C，将被寻求。 如果这项提案的目标实现，制备生物活性的新化学方法 分子将被开发出来。最终，这一贡献将促进新药剂的发现。 用来治疗人类疾病。

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 1-2 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 ROO Independent phase (years 3-5) 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 enantioenriched fused and bicyclic ring systems beginning from simple, prochiral starting materials. Finally, the asymmetric total syntheses of two potent antiinflammatory 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.