DNA 编码文库的 DNA 兼容铜/TEMPO 氧化。
DNA-Compatible Copper/TEMPO Oxidation for DNA-Encoded Libraries.
机构信息
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
出版信息
Bioconjug Chem. 2023 Aug 16;34(8):1380-1386. doi: 10.1021/acs.bioconjchem.3c00254. Epub 2023 Aug 4.
Abstract
Aldehydes are important synthons for DNA-encoded library (DEL) construction, but the development of a DNA-compatible method for the oxidation of alcohols to aldehydes remains a significant challenge in the field of DEL chemistry. We report that a copper/TEMPO catalyst system enables the solution-phase DNA-compatible oxidation of DNA-linked primary activated alcohols to aldehydes. The semiaqueous, room-temperature reaction conditions afford oxidation of benzylic, heterobenzylic, and allylic alcohols in high yield, with DNA compatibility verified by mass spectrometry, qPCR, Sanger sequencing, and ligation assays. Subsequent transformations of the resulting aldehydes demonstrate the potential of this method for robust library diversification.
摘要
醛是 DNA 编码库（DEL）构建的重要合成子，但在 DEL 化学领域，开发一种与 DNA 兼容的醇氧化为醛的方法仍然是一个重大挑战。我们报告称，铜/TEMPO 催化剂体系能够实现 DNA 连接的伯活化醇在溶液相中与 DNA 兼容的氧化为醛。半水相、室温反应条件可高产率地氧化苄基、杂苄基和烯丙基醇，通过质谱、qPCR、Sanger 测序和连接测定验证了 DNA 的兼容性。随后对生成的醛进行转化，证明了该方法在构建丰富多样的文库方面的潜力。
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