Development of baker's yeast-mediated bioreduction for preparin of optically active glycidol derivatives

酵母介导的生物还原前手性酮已被公认为一种有用的合成有机化学技术。本研究是开发一种酵母介导的生物还原法制备手性仲醇的方法。最近，我们报道了一种新的酵母介导的生物还原过程，使用乙醇代替糖作为能量来源。新工艺比原工艺更高效、更清洁，应该适合批量生产。利用酵母介导生物还原法研究了新工艺对乙酰乙酸乙酯的生物还原，可大规模制备光学纯度高的(S)-(+)- 3-羟基丁酸乙酯。通过在生物还原过程中应用补料间歇操作，提高了产品的产率和对映体过量。在此基础上，选择了气泡塔反应器进行工艺放大。该反应器大规模生物还原效果良好，最终反应介质为6% (w/w) (S)- 3-羟基丁酸乙酯和> 99% ee.2。通过酵母介导的生物还原(R)-(-)-1,2-丙二醇，乙二醇的脱氧衍生物(R)-(-)-1,2-丙二醇，通过上述相同的程序，由酵母介导的乙醇生物还原生产。（>99% ee, 300 g/L）用面包酵母处理(*)-1,2-丙二醇，去除(R)-(-)-1,2-丙二醇选择性氧化产生的乙酰，得到(S)-(-)-1,2-丙二醇（S)-(-)-1,2-丙二醇）。该方法是酵母介导制备手性醇的新方法。

The baker's yeast-mediated bioreduction of prochiral ketones has been recognized as a useful technique for synthetic organic chemist. This research is to develop a procedure for preparing chiral secondary alcohol by yeast-mediated bioreduction.Recently, we reported a new procedure for the yeast-mediated bioreduction using ethanol instead of sugar as the energy source. The new procedure is more efficient and clean than the original procedure, and it should be suitable for mass production.1. Large-scale preparation of (S)-ethyl 3-hydroxybutanoate with a high enantiomeric excess through baker's yeast-mediated bioreduction The yeast-mediated bioreduction of ethyl acetoacetate by the new procedure was investigated to produce (S)-(+)-ethyl 3-hydroxybutanoate with high optical purity on a large scale. Improvements in the yield and the enantiomeric excess of the product were accomplished by applying the fed-batch operation to the procedure of the bioreduction. Then, a bubble-column reactor was chosen for the scale-up of the procedure. The reactor favorably underwent bioreduction in the large scale and the final reaction medium contained 6 % (w/w) (S)-ethyl 3-hydroxybutanoate with > 99 % ee.2. Large-scale preparation of (R)-(-)-1,2-propanediol with a high enantiomeric excess through baker's yeast-mediated bioreduction (R)-(-)-1,2-Propanediol, deoxy derivative of glycidol, was produced by the yea st-mediated bioreduction of acetol through the same procedure mentioned above. (>99% ee, 300 g/L)3. Preparation of (S-)(-)-1,2-propanediol (S)-(-)-1,2-Propanediol was obtained by treatment of (*)-1,2-propanediol with baker's yeast followed by removal of the acetol produced by selective oxidation of (R)-(-)-1,2-propanediol. The procedure is the new one on yeast-mediated preparation of chiral alcohols.