光氧化还原催化 DNA 编码库合成中的开放空间烷基化反应。
Open-Air Alkylation Reactions in Photoredox-Catalyzed DNA-Encoded Library Synthesis.
机构信息
Roy and Diana Vagelos Laboratories, Department of Chemistry , University of Pennsylvania , 231 South 34th Street , Philadelphia , Pennsylvania 19104-6323 , United States.
GlaxoSmithKline , 1250 South Collegeville Road , Collegeville , Pennsylvania 19426 , United States.
出版信息
J Am Chem Soc. 2019 Feb 27;141(8):3723-3732. doi: 10.1021/jacs.9b00669. Epub 2019 Feb 12.
Abstract
DNA-encoded library (DEL) technology is a powerful tool commonly used by the pharmaceutical industry for the identification of compounds with affinity to biomolecular targets. Success in this endeavor lies in sampling diverse chemical libraries. However, current DELs tend to be deficient in C(sp) carbon counts. We report unique solutions to the challenge of increasing both the chemical diversity of these libraries and their C(sp) carbon counts by merging Ni/photoredox dual catalytic C(sp)-C(sp) cross-coupling as well as photoredox-catalyzed radical/polar crossover alkylation protocols with DELs. The successful integration of multiple classes of radical sources enables the rapid incorporation of a diverse set of alkyl fragments.
摘要
DNA 编码文库 (DEL) 技术是制药行业常用的一种强大工具，用于鉴定与生物分子靶标具有亲和力的化合物。这项工作的成功在于对不同的化学文库进行采样。然而，目前的 DEL 往往缺乏 C(sp) 碳原子数。我们报告了通过合并 Ni/光氧化还原双催化 C(sp)-C(sp) 交叉偶联以及光氧化还原催化的自由基/极性交叉烷基化反应与 DEL 来增加这些文库的化学多样性和 C(sp) 碳原子数的独特解决方案。多种自由基源的成功整合使得快速引入各种烷基片段成为可能。
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