Abstract

The biocatalytic asymmetric reduction of prochiral ketones is a significant transformation in organic chemistry as chiral carbinols are biologically active molecules and may be used as precursors of many drugs. In this study, the bioreduction of 1-(benzo [d] [1,3] dioxol-5-yl) ethanone for the production of enantiomerically pure (S)-1-(1,3-benzodioxal-5-yl) ethanol was investigated using freeze-dried whole-cell of Lactobacillus fermentum P1 and the reduction conditions was optimized with a D-optimal experimental design-based optimization methodology. This is the first study using this optimization methodology in a biocatalytic asymmetric reduction. Using D-optimal experimental design-based optimization, optimum reaction conditions were predicted as pH 6.20, temperature 30 °C, incubation time 30 h, and agitation speed 193 rpm. For these operating conditions, it was estimated that the product could be obtained with 94% enantiomeric excess (ee) and 95% conversion rate (cr). Besides, the actual ee and cr were found to be 99% tested under optimized reaction conditions. These findings demonstrated that L. fermentum P1 as an effective biocatalyst to obtain (S)-1-(1,3-benzodioxal-5-yl) ethanol and with the D-optimal experimental design-based optimization, this product could be obtained with the 99% ee and 99% cr. Finally, the proposed mathematical optimization technique showed the applicability of the obtained results for asymmetric reduction reactions.

摘要

前手性酮的生物催化不对称还原是有机化学的重大转变，因为手性甲醇是生物活性分子，可用作许多药物的前体。在本研究中，生物还原 1-(苯并 [d] [1,3] dioxol-5-yl) 乙酮用于生产对映体纯 ( S )-1-(1,3-benzodioxal-5-yl) 乙醇使用发酵乳杆菌P1的冻干全细胞进行研究，并使用基于D最佳实验设计的优化方法优化还原条件。这是在生物催化不对称还原中使用这种优化方法的第一项研究。使用D-基于优化实验设计的优化，预测的最佳反应条件为 pH 6.20、温度 30 °C、孵育时间 30 h、搅拌速度 193 rpm。对于这些操作条件，估计可以得到具有 94% 对映体过量 (ee) 和 95% 转化率 (cr) 的产品。此外，在优化的反应条件下，实际 ee 和 cr 的测试率为 99%。这些发现表明，发酵乳杆菌P1 作为获得 ( S )-1-(1,3-benzodioxal-5-yl) 乙醇的有效生物催化剂，并与D-基于优化实验设计的优化，该产品可以获得 99% ee 和 99% cr。最后，所提出的数学优化技术表明了所得结果对不对称还原反应的适用性。