Large screening of DNA-compatible reaction conditions for Suzuki and Sonogashira cross-coupling reactions and for reverse amide bond formation
Large screening of DNA-compatible reaction conditions for Suzuki and Sonogashira cross-coupling reactions and for reverse amide bond formation
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DOI：
10.1016/j.bmc.2021.116206
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发表时间：
2021-05-24
影响因子：
3.5
通讯作者：
Neri, Dario
中科院分区：
文献类型：
--
作者：
Favalli, Nicholas;Bassi, Gabriele;Neri, Dario
DNA 编码化学文库合成和筛选的进展关键取决于 DNA 相容反应的可用性，这些反应能够以高产率和优异的纯度生产大量可能的构建模块。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，我们的目标是优化铃木和园头反应，将我们的结果与之前发布的程序进行比较。我们使用 606 种结构单元（包括硼酸、频哪醇硼烷和末端炔烃）测试了改进条件的性能，84% 的测试分子实现了 >70% 的转化率。此外，我们描述了酰胺键在 DNA 上合成的有效实验条件，从携带羧酸部分和 300 种伯胺、仲胺和芳香胺的 DNA 衍生物开始，因为酰胺键由于其出色的 DNA 相容性而经常出现在 DNA 编码的化学文库中。
Progress in DNA-encoded chemical library synthesis and screening crucially relies on the availability of DNAcompatible 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.