DNA-Compatible Synthesis of α,β-Epoxyketones for DNA-Encoded Chemical Libraries

被引：13

作者：

Gao, Yuting ^{[1
]}

Zhao, Guixian ^{[1
]}

He, Pengyang ^{[1
]}

Zhang, Gong ^{[1
,2
]}

Li, Yangfeng ^{[1
,2
]}

Li, Yizhou ^{[1
,2
,3
]}

机构：

[1] Chongqing Univ, Innovat Drug Res Ctr, Sch Pharmaceut Sci, Chongqing Key Lab Nat Prod Synth & Drug Res, Chongqing 401331, Peoples R China

[2] Chongqing Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Chongqing 401331, Peoples R China

[3] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400044, Peoples R China

来源：

BIOCONJUGATE CHEMISTRY | 2022年 / 33卷 / 01期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

DISCOVERY; INHIBITORS; TECHNOLOGY; POTENT;

D O I：

10.1021/acs.bioconjchem.1c00567

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

As a powerful platform in drug discovery, the DNA-encoded chemical library technique enables the generation of numerous chemical members with high structural diversity. Epoxides widely exist in a variety of approved drugs and clinical candidates, eliciting multiple pharmaceutical activities. Herein, we report a non-oxidative DNA-compatible synthesis of di-/trisubstituted alpha,beta-epoxyketones by implementing aldehydes and alpha-chlorinated ketones as abundant building blocks. This methodology was demonstrated to cover a broad substrate scope with medium-to-excellent conversions. Further structural diversification and transformation were also successfully explored to fully leverage alpha,beta-epoxyketone moiety.

引用

页码：105 / 110

页数：6

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