To develop a practical scalable approach to (R)-tetrahydrofuran-2-carboxylic acid (THFC) 1, a chiral building block for furopenem 2, enantioselective hydrolysis of its esters is explored: When ethyl (±)-tetrahydrofuran-2-carboxylate 3d (2 M, 288 g/L) is digested by an Aspergillusmelleus protease {0.2% (w/v)} in a 1.5 M potassium phosphate buffer (pH 8) for 20 h, enantioselective hydrolysis proceeds with E=60 to give (R)-THFC 1 in 94.4% ee. On separation from the left-over antipodal ester (S)-3d by partition, (R)-THFC 1 is treated with N,N-dicyclohexylamine (DCHA) in methyl ethyl ketone/methanol (5:1) to precipitate the crystalline salt 4 that contains (R)-THFC 1 of >99% ee in 22% overall yield from (±)-3d.

中文翻译：

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（R）-四氢呋喃-2-羧酸的可扩展化学酶制剂

为了开发一种实用的可扩展方法以制备（R）-四氢呋喃-2-羧酸（THFC）1（呋喃酮2的手性结构单元），研究了其酯的对映选择性水解：当（±）-四氢呋喃-2-羧酸乙酯3d（2M 288克/升）通过消化曲霉melleus蛋白酶{0.2％（W / v）}在1.5M的磷酸钾缓冲液（pH8）20小时，对映选择性水解继续进行ë = 60，得到（94.4％ee中的R）-THFC 1。上从左侧悬停对映酯（分离小号） - 3D由分区，（- [R）-THFC 1用在甲乙酮/甲醇（5：1）中的N，N-二环己胺（DCHA）处理，以沉淀结晶盐4，该结晶盐4含（R）-THFC 1的> 99％ee，总产率为（±）22％。 - 3D。