Ding Yun, Clark Matthew A
GlaxoSmithKline , Platform Technology & Science, ELT-Boston, 830 Winter Street, Waltham, Massachusetts 02451, United States.
ACS Comb Sci. 2015 Jan 12;17(1):1-4. doi: 10.1021/co5001037. Epub 2014 Dec 2.
The Suzuki-Miyaura cross-coupling is one of the most widely employed reactions in medicinal chemistry. To apply this reaction to DNA-encoded library technology (ELT), an alternative approach in the discovery of small molecule hits and leads, we explored the Suzuki-Miyaura cross-coupling on DNA-linked aryl halides. Pd(PPh3)4 was demonstrated to be an effective catalyst for cross-coupling with on-DNA halide substrates under aqueous conditions. It efficiently catalyzes the coupling of phenyl halides (iodide or bromide) and pyridinyl bromides with various boronic acids/esters, including challenging heterocyclic boronic acids/esters.
铃木-宫浦交叉偶联反应是药物化学中应用最广泛的反应之一。为了将此反应应用于DNA编码文库技术（ELT，一种发现小分子活性物质和先导化合物的替代方法），我们探索了在与DNA相连的芳基卤化物上进行铃木-宫浦交叉偶联反应。结果表明，Pd(PPh3)4是在水相条件下与DNA上卤化物底物进行交叉偶联的有效催化剂。它能有效催化卤代苯（碘化物或溴化物）和吡啶基溴化物与各种硼酸/硼酸酯的偶联反应，包括具有挑战性的杂环硼酸/硼酸酯。
