Metal-Free and Open-Air Arylation Reactions of Diaryliodonium Salts for DNA-Encoded Library Synthesis.
Metal-Free and Open-Air Arylation Reactions of Diaryliodonium Salts for DNA-Encoded Library Synthesis.
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用于 DNA 编码文库合成的二芳基碘鎓盐的无金属和开放空气芳基化反应
DOI：
10.1002/advs.202202790
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发表时间：
2022-09
期刊：
影响因子：
15.1
通讯作者：
Yang, Guang
中科院分区：
文献类型：
--
作者：
Xu, Hongtao;Tan, Tingting;Zhang, Yiyuan;Wang, Yan;Pan, Kangyin;Yao, Ying;Zhang, Shuning;Gu, Yuang;Chen, Wanting;Li, Jie;Dong, Hewei;Meng, Yu;Ma, Peixiang;Hou, Wei;Yang, Guang
一个成功的DNA编码库（DEL）将由不同的骨架组成，并尽可能全面地覆盖化学空间，以充分发挥其在药物发现和化学生物学中的潜力。然而，缺乏用于亲核性和反应性较低的酚类的通用DNA芳基化方法，这对DEL包括二芳基醚（药物和天然产物中的特权化学型）构成了很大的障碍。这项工作描述了使用“底物活化”方法来解决DNA共轭酚的芳基化。二芳基碘鎓盐是一种高度亲电和反应性的芳基化试剂，用作Ar+源，以确保酚类和肟类在DNA上的高度选择性芳基化，同时具有高产率和DNA保真度。值得注意的是，新的DNA上芳基化反应可应用于含有酪氨酸侧链的肽的后期修饰，并合成现有药物分子的DNA标记类似物，如索拉非尼，一种已知的泛激酶抑制剂。新的DNA上二芳基碘鎓盐化学为DEL设计和合成提供了更大的灵活性。第一个DNA上的二芳基碘鎓盐（DAI）化学是通过底物活化策略开发的。开发了具有高产率和DNA保真度的酚类和肟类的选择性DNA芳基化方法。这些反应的应用潜力通过临床使用的药物索拉非尼的类似物的DNA上的中试合成和肽的后期修饰来证明。
A successful DNA‐encoded library (DEL) will consist of diverse skeletons and cover chemical space as comprehensive as possible to fully realize its potential in drug discovery and chemical biology. However, the lack of versatile on‐DNA arylation methods for phenols that are less nucleophilic and reactive poses a great hurdle for DEL to include diaryl ether, a privileged chemotype in pharmaceuticals and natural products. This work describes the use of “substrate activation” approach to address the arylation of DNA‐conjugated phenols. Diaryliodonium salt, a highly electrophilic and reactive arylation reagent, is employed as Ar+ sources to ensure highly selective on‐DNA arylation of phenols and oximes with both high yields and DNA fidelity. Notably, the new on‐DNA arylation reaction can be applied to the late‐stage modification of peptides containing tyrosine side‐chain and to synthesize DNA‐tagged analogues of existing drug molecules such as sorafenib, a known pan‐kinase inhibitor. The new on‐DNA diaryliodonium salts chemistry affords a greater flexibility in DEL design and synthesis. The first on‐DNA diaryliodonium slats (DAIs) chemistry is developed by substrate activation strategy. The selective on‐DNA arylation methods of phenols and oximes with both high yield and DNA fidelity are developed. The applicable potentiality of these reactions is demonstrated by pilot on‐DNA synthesis of analogs of clinically used drug sorafenib and late‐stage modification of peptides.
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影响因子：
5.2
作者：
Badir, Shorouk O.;Sim, Jaehoon;Molander, Gary A.
通讯作者：
Molander, Gary A.
开发结合测定之外的 DNA 编码文库的策略
影响因子：
21.8
作者：
Huang, Yiran;Li, Yizhou;Li, Xiaoyu
通讯作者：
Li, Xiaoyu
影响因子：
7.3
作者：
Harris, Philip A.;Berger, Scott B.;Bertin, John
通讯作者：
Bertin, John
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影响因子：
3.5
作者：
Favalli N;Bassi G;Scheuermann J;Neri D
通讯作者：
Neri D
DOI：
10.3390/medicines4020039
发表时间：
2017-06-10
期刊：
Medicines (Basel, Switzerland)
影响因子：
--
作者：
Ferraz MC;Mano RA;Oliveira DH;Maia DSV;Silva WP;Savegnago L;Lenardão EJ;Jacob RG
通讯作者：
Jacob RG