Synthesis, Microtubule Binding, and Anti-Cancer Activity of Diarylmethanes

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开发，以及这些方法在合成将被评估为抗癌活性的先导化合物方面的应用。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。协作性 还将进行研究，以测试这些类似物抑制微管蛋白聚合的活性，以及对几种癌细胞株的广泛筛选。这个项目将直接 通过为新药剂的制备和对映体富含二芳基甲烷的药效团的治疗潜力的验证提供新战略，影响新药剂的开发。

DESCRIPTION (provided by applicant): This proposal outlines the development of new chemical methods for alkyl-alkyl cross-coupling reactions to form carbon-carbon bonds and application of these methods for synthesis of lead compounds that will be evaluated for anti-cancer activity. 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 anti-cancer agents. Collaborative studies to test the activity of these analogues for inhibition of tubulin polymerization, as well a broad screens against several cancer cell lines, will also be performed. This project will directly impact the development of new pharmaceutical agents by providing new strategies for their preparation and validation of the therapeutic potential of the enantioenriched diarylmethane pharmacophore.