Stereospecific Nickel-Catalyzed Cross-Coupling for Pharmacophore Synthesis

描述（由申请人提供）：该提案概述了用于烷基-烷基交叉偶联反应以形成碳-碳键的新化学方法的开发。该项目的目标是为立体特异性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翻译到产物新形成的立体中心。这些方法将用于合成抗癌剂的二-和三芳基甲烷类似物。这些反应的发展将通过提供新的制备方法直接影响新药剂的开发。 公共卫生相关性：开发新的有机合成化学方法对于制备天然产物和其他生物活性分子进行初步生物学研究，临床试验和市场生产至关重要。尽管合成化学的先进状态仍然存在严重的挑战。该提案描述了新的化学反应的发展，将解决这些挑战之一，交叉偶联反应，形成三级立体中心与绝对立体化学的控制。

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.