The enantioselective oxyfunctionalisation of C−H bonds is a highly interesting reaction, as it provides access to chiral alcohols that are important pharmaceutical building blocks. However, it is hard to achieve using traditional methods. One way in which it can be achieved is through the action of oxidative enzymes. Although many reports of the oxyfunctionalisation capabilities of enzymes at an analytical scale have been published, reports on the use of enzymes to achieve oxyfunctionalisation on a synthetically relevant scale are fewer. Here, we describe the scale‐up of the conversion of 4‐ethylphenol to (R)‐1‐(4′‐hydroxyphenyl)ethanol using the flavin‐dependent enzyme vanillyl alcohol oxidase. The process was optimised by testing different reaction media and substrate and enzyme concentrations and by performing it under an oxygen atmosphere. Under optimised reaction conditions, 4.10 g (R)‐1‐(4′‐hydroxyphenyl)ethanol at 97% ee was obtained from 10 g 4‐ethylphenol (isolated yield 36%). These results highlight some of the challenges that can be encountered during scale‐up of an enzymatic oxyfunctionalisation process to a synthetically relevant scale and will be of use for the development of enzymatic processes for the synthesis of industrially relevant compounds.

中文翻译：

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香草醛醇氧化酶的多克规模酶促合成（R）-1-（4'-羟基苯基）乙醇

CH键的对映选择性氧基官能化是一个非常有趣的反应，因为它提供了获得重要药物组成部分的手性醇的途径。但是，使用传统方法很难实现。一种可以实现的方法是通过氧化酶的作用。尽管已经发表了许多关于酶的氧官能化能力的分析报告，但有关使用酶以合成相关规模实现氧官能化的报告却很少。在这里，我们描述了4-乙基苯酚向（R基）-1-（4'-羟基苯基）使用依赖黄素的酶香草醇氧化酶乙醇。通过测试不同的反应介质，底物和酶的浓度，并在氧气气氛下进行操作，对工艺进行了优化。在最佳反应条件下，从10 g 4-乙基苯酚中获得4.10 g（R）-1-（4'-羟基苯基）乙醇，其ee值为97％（分离产率为36％）。这些结果凸显了在将酶的氧化官能化工艺放大至合成相关规模时可能会遇到的一些挑战，这些挑战将可用于开发用于合成工业相关化合物的酶工艺。