Accessing New Chemical Space via Organic Synthesis

通过有机合成进入新的化学空间

• 批准号: 9977334
• 负责人: GARY A MOLANDER
• 金额: $ 2.99万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977334
• 关键词: 3-Dimensional; Address; Amaze; Area; Carbon; Catalysis; Chemicals; Chemistry; Coupling; DNA; Development; Disease; Grant; Human; Hybrids; Industrialization; Knowledge; Libraries; Methods; Molecular; Organic Synthesis; Process; Research; Research Project Summaries; Sampling; Science; Scientist; Structure; System; Technology; Transcend; base; cost; drug discovery; innovation; invention; novel; screening; small molecule; tool

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.

项目摘要 本提案中概述的研究将在以下三个中建立新知识 区域：1）将探索获得新型硼嗪结构的访问，这些结构的实用性 全碳系统的等值剂，可预测，高度选择性，多功能的宝贵功能 将展示核心结构。 2）Photoredox/Ni双重催化用于SP3-的交叉偶联 杂交中心在我们的小组中率先开发。这些是具有变革性的过程， 以优雅而实用的方式提供了必要的工具，以打开3D的广阔新区域 高度功能化的子结构中通过晚期交叉耦合进行化学空间。 持续的创新将集中在三个子主题上：Photoredox/ni dual的进一步扩展 催化作用，光电毒素应用于新的自由基转化， 基于光毒素化学的新自由基/极性跨界转化的发明。 3） 由于在当前赠款范围内取得了进步，这是一个绝佳的新机会 扩展我们的化学反应已经出现，它将为药物发现提供转型的新工具。 组中开发的方法正在应用于DNA编码库（DEL）合成，A 具有轻松采样四到五个数量级的能力的技术 与任何其他可用的高通量小分子相比 筛选方法。人们普遍承认，全面实施的主要障碍 DEL Technology是强大，多功能，与DNA兼容的化学的发展， 目前在范围和应用程序上受到极大限制。该提议中概述的化学反应 解决这个关键差距，因此有能力彻底改变药物发现 过程。