光/酶催化自由基酰化合成β-酮腈

Photobiocatalytic Radical Acylation Facilitates the Synthesis of β-Ketonitriles

摘要

建立了一种可见光驱动下焦磷酸硫胺素(ThDP)依赖酶与光催化剂协同催化的新方法，实现了芳香醛与偶氮腈的自由基酰化反应，高效合成了一系列β-酮腈类化合物.该体系利用光催化产生氰烷基自由基，并与酶活性中心内由ThDP稳定的酮基自由基发生交叉偶联，在温和条件下构建C—C键.此反应具有广泛的底物适用性和良好的官能团兼容性.本研究是首例光生物催化合成β-酮腈的报道，为绿色合成及酶催化非天然转化提供了新策略.

Abstract

This paper reports a novel photobiocatalytic system that integrates thiamine diphosphate（ThDP）-dependent enzymes with photoredox catalysis to achieve radical acylation between aromatic aldehydes and azonitrile reagents under visible light irradiation. This method enables the efficient synthesis of β-ketonitriles via cross-coupling of an enzyme-bound ThDP-derived ketyl radical and a photogenerated cyanoalkyl radical under mild conditions. The reaction exhibits a broad substrate scope and good functional group compatibility. This work represents the first example of synthesizing β-ketonitriles via photobiocatalysis，offering a new strategy for sustainable synthesis and expanding the toolbox for non-natural enzyme catalysis.

关键词

光生物催化 / 自由基酰化 / 焦磷酸硫胺素 / β-酮腈

Key words

Photobiocatalysis / Radical acylation / Thiamine diphosphate（ThDP） / β-Ketonitrile

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基金资助

国家自然科学基金(22407132)