Nitrogen heterocycles are commonly found in bioactive natural products and drugs. However, the biocatalytic tools for nitrogen heterocycle synthesis are limited. Herein, we report the discovery of vanillyl alcohol oxidases (VAOs) as efficient biocatalysts for the one‐pot synthesis of 2‐aryl thiazolines from various 4‐hydroxybenzaldehydes and aminothiols. The wild‐type biocatalyst features a broad scope of 4‐hydroxybenzaldehydes. Though the scope of aminothiols is limited, it could be improved via semi‐rational protein engineering, generating a variant to produce previously inaccessible cysteine‐derived bioactive 2‐aryl thiazolines using the wild‐type VAO. Benefiting from the derivatizable functional groups in the enzymatic products, we further chemically modified these products to expand the chemical space, offering a new chemoenzymatic strategy for the green and efficient synthesis of structurally diverse 2‐aryl‐thiazoline derivatives to prompt their use in drug discovery and catalysis.

中文翻译：

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使用香草醇氧化酶从 4-羟基苯甲醛化学酶法合成 2-芳基噻唑啉


氮杂环常见于具有生物活性的天然产物和药物中。然而，用于氮杂环合成的生物催化工具是有限的。在此，我们报告发现香草醇氧化酶（VAO）作为有效的生物催化剂，用于从各种 4-羟基苯甲醛和氨基硫醇一锅合成 2-芳基噻唑啉。野生型生物催化剂含有广泛的 4-羟基苯甲醛。尽管氨基硫醇的范围有限，但可以通过半理性蛋白质工程对其进行改进，生成一种变体，使用野生型 VAO 生产以前无法获得的半胱氨酸衍生的生物活性 2-芳基噻唑啉。受益于酶产物中的可衍生官能团，我们进一步对这些产物进行化学修饰以扩大化学空间，为绿色高效合成结构多样的2-芳基-噻唑啉衍生物提供新的化学酶策略，以促进其在药物发现中的应用和催化作用。