Stereospecific Nickel-Catalyzed Cross-Coupling for Pharmacophore Synthesis

描述(由申请人提供)：本建议书概述了烷基-烷基交叉偶联反应形成碳-碳键的新化学方法的发展。这个项目的目标是为立体特异的交叉偶联反应产生新的策略，其中来自亲电反应伙伴的立体化学信息被转化到新形成的产物的立体生成中心。这些方法将用于合成抗癌药物的二芳基和三芳基甲烷类似物。这些反应的发展将为新药物的制备提供新的方法，从而直接影响到新药物的发展。 与公众健康相关：有机合成的新化学方法的开发对于制备用于初步生物学研究、临床试验和市场生产的天然产物和其他生物活性分子至关重要。尽管合成化学处于先进状态，但仍然存在严峻的挑战。这项建议描述了将解决这些挑战之一的新化学反应的发展，交叉偶联反应形成了绝对立体化学控制的三级立体中心。

DESCRIPTION (provided by applicant): This proposal outlines the development of new chemical methods for alkyl-alkyl cross- coupling reactions to form carbon-carbon bonds. The objectives of this project are to generate new strategies for stereospecific cross-coupling reactions, where the stereochemical information from the electrophilic reaction partner is translated to the newly formed stereogenic center of the product. These methods will be utilized in the synthesis of di- and triarylmethane analogs of anticancer agents. The development of these reactions will directly impact the development of new pharmaceutical agents by providing new methods for their preparation. PUBLIC HEALTH RELEVANCE: The development of new chemical methods for organic synthesis is essential in the preparation of natural products and other bioactive molecules for preliminary biological studies, clinical trials, and production for market. Despite the advanced state of synthetic chemistry serious challenges remain. This proposal describes the development of new chemical reactions that will address one of these challenges, cross-coupling reactions that form tertiary stereogenic centers with control of absolute stereochemistry.