Radical-Mediated Atom-Transfer Strategies for Chemical Synthesis

施密特-项目总结 自由基物种在生物系统中发挥重要作用，不仅与功能失调的细胞增殖有关， 其他疾病途径，而且在生命所必需的基本健康过程中。了解反应性 开壳层碳、氧、硫和其他杂原子中心的自由基中间体的分布对于 了解这些过程是如何发生的，并提出合理的机制，目前不明确的 途径。 研究和理解自由基中间体的反应性特征也可以导致新的 有可能简化现有药物合成的合成方法 更有效，并提供下一代治疗方法和成像，诊断， 治疗和预防。 这项建议是建立在PI的研究小组使用磷基 从非传统前体中暴露碳和杂原子中心的自由基的试剂。这个一般 该平台已经实现了C-N键的区域选择性构建，该C-N键存在于大部分的 FDA批准药物，并经常参与生物活性的模式。这些激进分子 这些方法利用原子转移过程的有利热力学来实现新的键的形成 从常见的化学功能。未来的研究将继续探索这一普遍的潜力。 通过调查其他常见功能组的能力，以类似的方式揭露平台，以实现 新的债券形成。我们期望这项工作可能会导致复杂分子构建的新策略 用于制备化学生物学中的新分子治疗剂和工具。

Schmidt – Project Summary Radical species play important roles in biological systems linked not only to dysfunctional cell proliferation and other disease pathways, but also in essential healthy processes necessary for life. Understanding the reactivity profiles of open-shell carbon, oxygen, sulfur, and other heteroatomic-centered radical intermediates is crucial to understanding how these processes occur and to propose reasonable mechanisms for currently ill-defined pathways. Studying and understanding reactivity profiles of radical intermediates can also result in the development of new synthetic methodologies with the potential to streamline and make the synthesis of existing pharmaceuticals more efficient and provide access to the next generation of therapeutics and tools for imaging, diagnosis, treatment, and prevention. This proposal is built on the prior and concurrent efforts of the PI’s research group using phosphorous-based reagents to unmask carbon and heteroatom-centered radicals from untraditional precursors. This general platform has achieved the regioselective construction of C-N bonds which are present in a substantial portion of FDA approve pharmaceuticals and are often involved in the mode of biological activity. These radical-mediated approaches leverage the favorable thermodynamics of atom-transfer processes to achieve new bond formations from common chemical functionalities. Future studies will continue to explore the potential of this general platform by investigating the ability of other common functional groups to be analogously unmasked to achieve new bond formations. We anticipate that this work may lead to new strategies in complex molecule construction for use in the preparation of new molecular therapeutics and tools in chemical biology.