Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, 401331, Chongqing, P. R. China.
Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, 401331, Chongqing, P. R. China.
Bioconjug Chem. 2022 Jan 19;33(1):105-110. doi: 10.1021/acs.bioconjchem.1c00567. Epub 2021 Dec 20.
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 α,β-epoxyketones by implementing aldehydes and α-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 α,β-epoxyketone moiety.
作为药物发现的强大平台，DNA 编码化学库技术能够生成具有高度结构多样性的大量化学成员。环氧化物广泛存在于各种已批准的药物和临床候选物中，具有多种药物活性。在此，我们报告了一种非氧化的、与 DNA 兼容的二-/三取代α,β-环氧酮的合成方法，该方法使用醛和α-氯代酮作为丰富的构建块。该方法表现出广泛的底物范围，中等至优异的转化率。进一步的结构多样化和转化也成功地进行了探索，以充分利用α,β-环氧酮部分。
