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

面包酵母介导的前手性酮的生物还原反应已被公认为是一种有用的有机合成技术。本研究旨在开发一种利用酵母菌生物还原制备手性仲醇的新方法，最近我们报道了一种以乙醇代替糖为能源的酵母菌生物还原制备手性仲醇的新方法。新工艺比原来的工艺更高效、更清洁，更适合大规模生产。面包酵母生物还原法大规模制备高光学纯度的（S）-（+）-3-羟基丁酸乙酯研究了酵母生物还原乙酰乙酸乙酯的新工艺，实现了大规模制备高光学纯度的（S）-（+）-3-羟基丁酸乙酯。将补料分批操作应用于生物还原过程中，提高了产物的收率和对映体过量。然后，选择鼓泡塔反应器进行放大。反应器进行了大规模的生物还原反应，最终反应介质中含有6%（w/w）的（S）-3-羟基丁酸乙酯，ee> 99%.利用面包酵母还原丙酮醇大规模制备高对映体过量的（R）-（-）-1，2-丙二醇（R）-（-）-1，2-丙二醇是缩水甘油的脱氧衍生物。（> 99%ee，300g/L）3.（R）-（-）-1，2-丙二醇选择性氧化生成丙酮醇，经面包酵母处理后得到（S）-（-）-1，2-丙二醇。该方法是酵母菌介导合成手性醇的新方法。

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.