Accessing New Chemical Space via Organic Synthesis

项目总结 本提案中概述的研究将在以下三个方面建立新的知识 领域：1)将探索获得新的硼氮卓类结构，以及这些结构的有用性 全碳体系的同位素体具有可预测性、高选择性、多功能化的价值 将演示核心结构。2)SP3-的光氧化还原/镍双催化交叉偶联 杂交中心是我们小组的先驱。这些都是变革性的过程， 以优雅而实用的方式，提供了必要的工具，开辟了广阔的3D新领域 在高度功能化的亚结构中通过后期交叉耦合形成化学空间。 持续创新将集中在三个小主题上：进一步扩大光氧化还原/镍双 催化，光氧化还原在新的自由基转化中的应用，以及 基于光氧化还原化学的新型自由基/极性交叉转换的发明。3) 由于在当前赠款范围内取得了进展，这是一个令人惊叹的新机会 扩展我们的化学已经出现，这将为药物发现提供变革性的新工具。 该小组开发的方法正被应用于DNA编码库(DEL)的合成， 能够轻松地多取样四到五个数量级的技术 化学空间，比任何其他可用的高通量小分子便宜 筛查方法。人们普遍认为，全面执行《公约》的主要障碍是 DEL技术是强大的、多功能的、与DNA兼容的化学的发展，这是 目前在范围和应用上都非常有限。这项提案中概述的化学成分 解决了这一关键差距，从而有能力使药物发现发生革命性变化 进程。

PROJECT SUMMARY The research outlined within this proposal will establish new knowledge in the following three areas: 1) Access to novel borazine structures will be explored, and the usefulness of these isosteres of all-carbon systems for predictable, highly selective, polyfunctionalization of valuable core structures will be demonstrated. 2) Photoredox/Ni dual catalysis for cross-coupling of sp3- hybridized centers was pioneered in our group. These are transformative processes that have, in an elegant and practical manner, provided the necessary tools to open vast new areas of 3D chemical space through late-stage cross-coupling in highly functionalized substructures. Continued innovation will focus on three subtopics: further expansion of the photoredox/Ni dual catalysis, application of photoredox for application to novel radical transformations, and the invention of novel radical/polar crossover transformations based on photoredox chemistry. 3) As a result of progress made within the scope of current grants, an amazing new opportunity to expand our chemistry has arisen that will provide transformational new tools for drug discovery. Methods developed in the group are being applied to DNA Encoded Library (DEL) synthesis, a technology that possesses the capability to sample easily four to five orders of magnitude more chemical space, less expensively, than any other available high-throughput, small molecule screening methods. It is widely acknowledged that the major hurdle to full implementation of DEL technology is the development of robust, versatile, DNA-compatible chemistry, which is currently exceedingly limited in scope and application. The chemistry outlined in this proposal addresses this critical gap, and thus has the capability to revolutionize the drug discovery process.