Accessing New Chemical Space via Organic Synthesis

通过有机合成进入新的化学空间

基本信息

批准号：
10408077
负责人：
GARY A MOLANDER
金额：
$ 56万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2023-06-30
项目状态：
已结题

项目摘要

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.

项目概要本提案中概述的研究将在以下三个方面建立新知识领域： 1）将探索新型环硼氮烷结构的获取，以及这些结构的有用性全碳系统的等排体，用于有价值的可预测、高选择性、多功能化将展示核心结构。 2）光氧化还原/Ni双催化sp3-交叉偶联杂交中心是我们小组首创的。这些都是变革性的过程，以优雅而实用的方式，提供了打开 3D 广阔新领域所需的工具通过高度功能化的子结构中的后期交叉耦合来形成化学空间。持续创新将集中于三个子主题：进一步扩展光氧化还原/镍双催化、光氧化还原在新型自由基转化中的应用，以及发明基于光氧化还原化学的新型自由基/极性交叉变换。 3）由于在当前赠款范围内取得的进展，这是一个令人惊奇的新机会扩展我们的化学已经出现，它将为药物发现提供变革性的新工具。该小组开发的方法正应用于 DNA 编码库 (DEL) 合成，这是一种能够轻松采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、小分子更便宜筛选方法。人们普遍承认，全面实施《公约》的主要障碍是 DEL 技术是稳健、多功能、DNA 相容化学的发展，目前的范围和应用极其有限。本提案中概述的化学反应解决了这一关键差距，从而有能力彻底改变药物发现过程。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

1,2-Radical Shifts in Photoinduced Synthetic Organic Transformations: A Guide to the Reactivity of Useful Radical Synthons.

DOI：
10.1021/acsorginorgau.2c00032
发表时间：
2022-12-07
期刊：
ACS ORGANIC & INORGANIC AU
影响因子：
0
作者：
Matsuo, Bianca;Granados, Albert;Majhi, Jadab;Sharique, Mohammed;Levitre, Guillaume;Molander, Gary A.
通讯作者：
Molander, Gary A.

Practical, scalable, and transition metal-free visible light-induced heteroarylation route to substituted oxindoles.