We first developed a novel and efficient chemoenzymatic process to prepare (S)-1-(pyridin-4-yl)-1,3-propanediol, a vital HepDirect prodrug intermediate, from inexpensive and commercially available isonicotinic acid. Through this process, we provide a creative way to obtain the key chiral intermediate, β-hydroxyester, with ketoreductase (KRED) EA. After optimization of the process, we performed the reaction on a 100 g scale with a substrate concentration of up to 150 g/L, a yield of 93%, and an ee value of up to 99.9%. Additionally, we used a simple and effective NaBH₄/MgCl₂ reduction system to obtain (S)-1-(pyridin-4-yl)-1,3-propanediol with >99.9% ee and an 80% yield. This novel chemoenzymatic process has the potential to be a cost-effective and environmentally friendly process suitable for industrial use.

中文翻译：

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（S）-1-（吡啶-4-基）-1,3-丙二醇的新型化学酶法开发

我们首先开发了一种新颖而有效的化学酶法，以廉价且可商购的异烟酸制备（S）-1-（吡啶-4-基）-1,3-丙二醇，这是一种至关重要的HepDirect前药中间体。通过此过程，我们提供了一种创新方法，可通过酮还原酶（KRED）EA获得关键的手性中间体β-羟基酯。在优化工艺之后，我们以100 g规模进行了反应，底物浓度最高为150 g / L，产率为93％，ee值最高为99.9％。此外，我们使用了一种简单有效的NaBH ₄ / MgCl ₂还原系统来获得（S）-1（吡啶-4-基）-1,3-丙二醇，ee大于99.9％，收率80％。这种新颖的化学酶法工艺有可能成为适合工业应用的经济高效且环保的工艺。