ETH Zürich, Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland; Philochem AG, Libernstrasse 3, 8112 Otelfingen, Switzerland.
ETH Zürich, Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
Bioorg Med Chem. 2021 Jul 1;41:116206. doi: 10.1016/j.bmc.2021.116206. Epub 2021 May 9.
Progress in DNA-encoded chemical library synthesis and screening crucially relies on the availability of DNA-compatible reactions, which proceed with high yields and excellent purity for a large number of possible building blocks. In the past, experimental conditions have been presented for the execution of Suzuki and Sonogashira cross-coupling reactions on-DNA. In this article, our aim was to optimize Suzuki and Sonogashira reactions, comparing our results to previously published procedures. We have tested the performance of improved conditions using 606 building blocks (including boronic acids, pinacol boranes and terminal alkynes), achieving >70% conversion for 84% of the tested molecules. Moreover, we describe efficient experimental conditions for the on-DNA synthesis of amide bonds, starting from DNA derivatives carrying a carboxylic acid moiety and 300 primary, secondary and aromatic amines, as amide bonds are frequently found in DNA-encoded chemical libraries thanks to their excellent DNA compatibility.
DNA 编码化学库合成和筛选的进展关键依赖于 DNA 相容反应的可用性，这些反应具有高产率和优异的纯度，适用于大量可能的构建块。过去，已经提出了在 DNA 上执行 Suzuki 和 Sonogashira 交叉偶联反应的实验条件。在本文中，我们的目的是优化 Suzuki 和 Sonogashira 反应，将我们的结果与以前发表的程序进行比较。我们使用 606 个构建块（包括硼酸、频哪醇硼烷和末端炔烃）测试了改进条件的性能，对于 84%的测试分子，转化率超过 70%。此外，我们描述了从带有羧酸部分的 DNA 衍生物和 300 种伯、仲和芳胺起始的 DNA 上酰胺键合成的有效实验条件，因为酰胺键由于其与 DNA 的优异相容性而经常存在于 DNA 编码化学库中。
