Deracemization, the transformation of the racemate into a single stereoisomeric product in 100% theoretical yield, is an appealing but challenging option for the asymmetric synthesis of optically pure chiral compounds as important pharmaceutical intermediates. To enhance the synthesis of (R)-1,3-butanediol from the corresponding low-cost racemate with minimal substrate waste, we designed a stereoinverting cascade deracemization route and constructed the cascade reaction for the total conversion of racemic 1,3-butanediol into its (R)-enantiomer. This cascade reaction consisted of the absolutely enantioselective oxidation of (S)-1,3-butanediol by Candida parapsilosis QC-76 and the subsequent asymmetric reduction of the intermediate 4-hydroxy-2-butanone to (R)-1,3-butanediol by Pichia kudriavzevii QC-1. The key reaction conditions including choice of cosubstrate, pH, temperature, and rotation speed were optimized systematically and determined as follows: adding acetone as the cosubstrate at pH 8.0, a temperature of 30 °C, and rotation speed of 250 rpm for the first oxidation process; in the next reduction process, the optimal conditions were: adding glucose as the cosubstrate at pH 8.0, a temperature of 35 °C, and rotation speed of 200 rpm. By investigating the feasibility of the step-by-step method with one-pot experiment as a natural extension for performing the oxidation–reduction cascade, the step-by-step approach exhibited high efficiency for this cascade process from racemate to (R)-1,3-butanediol. Under optimal conditions, 20 g/L of the racemate transformed into 16.67 g/L of (R)-1,3-butanediol with 99.5% enantiomeric excess by the oxidation–reduction cascade system in a 200-mL bioreactor. The step-by-step cascade reaction efficiently produced (R)-1,3-butanediol from the racemate by biosynthesis and shows promising application prospects.

中文翻译：

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通过全细胞立体转化级联系统将相应的外消旋物脱硫，可以高度对映体选择性地合成（R）-1,3-丁二醇。

对于非对称合成光学纯的手性化合物作为重要的医药中间体而言，脱消旋（即外消旋体以100％的理论产率将外消旋体转变为单一的立体异构产物）是一个有吸引力但具有挑战性的选择。为了提高相应的低成本外消旋体的（R）-1,3-丁二醇的合成，同时将底物浪费降至最低，我们设计了一种立体转化级联脱消途径，并构建了将外消旋1,3-丁二醇完全转化为外消旋的级联反应（R）-对映体。该级联反应包括通过副念珠菌QC-76对（S）-1,3-丁二醇进行绝对对映选择性氧化，然后将中间体4-羟基-2-丁酮不对称还原为（R）-1,3-丁二醇由Pichia kudriavzevii QC-1提供。系统优化了包括共底物选择，pH，温度和旋转速度在内的关键反应条件，并确定了以下条件：第一次氧化时，在pH 8.0，温度为30°C和转速为250 rpm的条件下添加丙酮作为共底物处理; 在下一个还原过程中，最佳条件是：在pH 8.0，温度35°C和转速200 rpm的条件下添加葡萄糖作为共底物。通过研究一步法作为一锅自然实验进行氧化还原级联反应的自然延伸的可行性，逐步方法显示了从外消旋体到（R）-的级联过程的高效率1,3-丁二醇。在最佳条件下，将20 g / L的外消旋物转化为16.67 g / L的（R）-1,3-丁二醇与99。在200 mL生物反应器中，氧化还原级联系统对映体过量5％。通过逐步的级联反应，通过生物合成有效地从外消旋体制备了（R）-1,3-丁二醇，并显示出广阔的应用前景。