New Asymmetric Transformations and Chemical Synthesis of Natural Products

描述(申请人提供)：这项研究计划旨在开发新的和有效的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与Larry Overman教授一起进行一到两年的时间，涉及发现新的不对称Pd(II)催化的三氯乙酸烯丙酯反应。在这一方法学开发之前，将在有效合成小叶醌的背景下对其进行评估，小叶醌是一种小分子，对几种细胞系具有细胞毒性。R00独立阶段(3年至5年)将专注于发现不对称金属介导的偶联反应，以促进全碳四元立体中心的形成，这是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级联反应，从简单的前手性起始材料开始，快速构建富含对映体的稠环和双环体系。最后，将继续进行两种有效抗炎化合物甘露糖醇A和C的不对称全合成。 如果这项提议的目标得以实现，将开发新的化学方法来制备生物活性分子。最终，这一贡献将促进发现治疗人类疾病的新药物。

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.