Radical-Mediated Atom-Transfer Strategies for Chemical Synthesis

化学合成中自由基介导的原子转移策略

• 批准号: 10028985
• 负责人: Valerie Anne Schmidt
• 金额: $ 35.54万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10028985
• 关键词: Biochemical Process; Biological; Biology; Carbon; Cell Proliferation; Chemicals; Complex; Development; Diagnosis; Disease Pathway; FDA approved; Future; Imaging Device; Investigation; Lead; Life; Link; Mediating; Methodology; Methods; Molecular; Oxygen; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Phosphorus; Play; Preparation; Prevention; Process; Reagent; Research; Role; Sulfur; System; Therapeutic; Thermodynamics; Work; base; biological systems; chemical function; chemical synthesis; functional group; novel therapeutics; tool

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.

施密特-项目摘要 自由基物种在生物系统中扮演着重要的角色，不仅与功能失调的细胞增殖和 其他疾病途径，但也在生命所必需的健康过程中。了解反应性 开壳碳、氧、硫和其他以杂原子为中心的自由基中间体的轮廓对于 了解这些过程是如何发生的，并针对目前定义不清的情况提出合理的机制 小路。 研究和了解自由基中间体的反应性分布也可以导致新的 有可能简化和合成现有药物的合成方法 更高效，并提供使用下一代疗法和工具进行成像、诊断、 治疗和预防。 这一建议是建立在PI研究小组使用磷基的先前和同时努力的基础上的 将碳和杂原子为中心的自由基从非传统前体中揭示出来的试剂。这位将军 Platform已经实现了C-N键的区域选择性构建，这些C-N键存在于相当一部分 FDA批准了药品，并经常涉及到生物活性模式。这些由自由基介导的 方法利用原子转移过程的有利热力学来实现新的键形成 从常见的化学官能团。未来的研究将继续探索这一将军的潜力 平台通过调查其他常见功能基团的能力被类似地揭开来实现 形成新的纽带。我们预计，这项工作可能会导致复杂分子构建的新策略 用于化学生物学中新的分子疗法和工具的制备。