Enzymatic processes for the production of D-pantoyl lactone and related optically active hydroxylated compounds

用假丝酵母（Candida parapsilosis） IFO 0708或红酵母（Rhodotorula minuta） IFO 0920洗涤后的细胞孵育，发现酮antoyl内酯能有效地转化为D-(-)-pantoyl内酯。在5%的玉米浸泡液和5%的葡萄糖、蔗糖、麦芽糖或甘油中培养时，它们表现出较高的转化活性。在适宜的反应条件下，D-(-)-pantoyl内酯的量分别达到49.5g/l（94.4%e.e，摩尔产率99%）和89.9g/l（80.4%e.e，摩尔产率99%）。提出了一种由外消旋pantoyl内酯混合物合成D(-)-pantoyl内酯的新酶法。该过程包括将泛酰内酯的L(+)-异构体立体特异性氧化为酮antoyl内酯，然后将其不对称还原为D(-)-异构体。氧化过程以Nocardia asteroides AKU 2103细胞为催化剂，仅将L(+)-同分异构体转化为酮-pantoyl内酯，其余D(-)-同分异构体没有任何修饰。以80gl^<-1> DL-pantoyl内酯为底物，在最佳反应条件下，加入的L(+)-异构体的>90%转化为酮托antoyl内酯。在假丝酵母菌IFO 0784细胞的孵育下，积累在反应混合物中的酮antoyl内酯几乎特异性地转化为pantoyl内酯的D(-)-异构体。由于该工艺简单，不需要常规化学分解所必需的再消映步骤，因此对D(-)-pantoyl内酯的实际合成非常有利。

The efficient enzymatic conversion of ketopantoyl lactone to D-(-)-pantoyl lactone was found to take place on incubation with washed cells of Candida parapsilosis IFO 0708 or Rhodotorula minuta IFO 0920. They showed high conversion activity when grown with 5% corn steep liquor and 5% glucose, sucrose,maltose or glycerol.Under suitable reaction conditions the amounts of D-(-)-pantoyl lactone reached 49.5g/l(94.4%e.e; molar yield,99%) and 89.9g/l(80.4%e.e; molar yield,99%)with cells of R.minuta and C.parapsilosis,respectively.A novel enzymatic process for the synthesis of D(-)-pantoyl lactone from a racemic mixture of pantoyllactone was also developed.The process involves the stereospecific oxidation of the L(+)-isomer of pantoyl lactoneto ketopantoyl lactone followed by its asymmetric reduction to the D(-)-isomer. The oxidation is carried out with cells of Nocardia asteroides AKU 2103 as the catalyst, which convert only the L(+)-isomer of pantoyl lactone to keto-pantoyl lactone without any modification of the remaining D(-)-isomer.With 80gl^<-1> DL-pantoyl lactone as the substrate,>90%of the added L(+)-isomer was converted to ketopantoyl lactone under the optimum reaction conditions. The ketopantoyl lactone that accumulated in the reaction mixture was almost specifically converted to the D(-)-isomer of pantoyl lactone on incubation with cells of Candida parapsilosis IFO 0784. Scince this process is simple and requires no reracemization step, which is necessary for conventional chemical resolution, it is highly advantageous for the practical synthesis of D(-)-pantoyl lactone.