Asymmetric Reduction of Keto Acids by Use of Bakers' Yeast

(1)以含氧化还原酶的面包师酵母匀浆为底物，以NADPH为辅酶，对脂肪族δ酮酸进行不对称还原。产物与完整细胞的产物具有相同的构型(R)。两种产品的ee %也都在98%左右。由于匀浆的物质平衡较好，因此在完整的细胞中，底物部分丢失。然而，对于底物或产物通过细胞壁或细胞膜的渗透是否至关重要，没有得出结论。(2)金属盐的影响：加入浓度为1.5 mol/L的MnCl_2可使烘焙酵母的还原率由64%提高到84 89%。这一结果只出现在底物n-C_5H_<11>COCH_2CH_2CO_2H上，这是一个有趣但无法解释的现象。(3)面包师酵母不对称还原多功能型β， δ -二酮酸的主要还原产物为β -酮- δ -羟基酸，没有进一步还原为β， δ -二羟基酸。作为次要产物得到-羟基δ -酮酸，发现它很容易还原为- - δ -二羟基酸。所有手性碳原子的构型均为R， ee %为bb0 ~ 99% ee。羟基化合物可以环化成酮或羟基内酯。(4) baker酵母不对称还原β -氯-酮酸的工艺条件为：R=CH_3, config=S， 50 - 60%产率，> - 99% ee；R=C_2H_5， S, 10%, 68% ee；R=n-C_3H_7， R, 20%, 61% ee；R=n-C_4H_9 n-C_6H_<13>， R, 20%, >98% ee。

(1)Asymmetric Reduction by Use of Bakers' Yeast Homogenate Containing OxidoreductaseAliphatic delta-keto acids as substrate were reduced with the homogenate by use of NADPH as coenzyme. The products had the same configuration(R)as that for the products from the intact cells. The % ee was also>98% ee for both products. Since the material balance was better for the homogenate, it was suggested that the substrate was party lost in intact cells. However, no conclusion was derived about the possibility that the permeation of the substrate or the product through the cell wall or membrane is critical.(2)Effects of Metal SaltsAddition of MnCl_2 at a concentration of 1.5 mol/L enhanced the yield of bakers'yeast reduction from 64% to 84 89%. This result was found only for the substrate, n-C_5H_<11>COCH_2CH_2CO_2H, which is interesting but not explicable.(3)Asymmetric Reduction of Polyfunctional beta, delta-Diketo Acid by Use of Bakers' YeastThe main reduction product was beta-keto delta-hydroxy acid, which was found not to be reduced further to beta, delta-dihydroxy acid. beta-Hydroxy delta-keto acide was obtained as a minor product, which was found to be rather readily reduced to beta, delta-dihydroxy acid. The configuration was R for all chiral carbon atoms and the % ee was>99% ee. The delta-hydroxy compounds can be cyclized to beta-keto or beta-hydroxy delta-lactones.(4)Asymmetric Reduction of beta-Chloro gamma-Keto Acid by Use of Bakers' YeastRCOCHClCH_2CO_2H was reduced to the corresponding secondary alcohol : R=CH_3, config=S, 50 60% yield, >99% ee ; R=C_2H_5, S, 10%, 68% ee ; R=n-C_3H_7, R, 20%, 61% ee ; R=n-C_4H_9 n-C_6H_<13>, R, 20%, >98% ee.