羰基还原酶不对称还原(R)-6-氰基-5-羟基-3-羰基己酸叔丁酯

Asymmetric reduction of t-butyl 6-cyano-(5R)-hydroxy-3-carbonylhexanoate by carbonyl reductase

选择R-羰基还原酶和葡萄糖脱氢酶双酶,协同催化(R)-6-氰基-5-羟基-3-羰基己酸叔丁酯不对称还原制备阿托伐他汀关键手性合成子6-氰基-(3R,5R)-二羟基己酸叔丁酯。转化条件优化结果显示:在不添加外源性辅酶NADP(H)、菌体用量15.0 g/L、147.0 g/L(R)-6-氰基-5-羟基-3-羰基己酸叔丁酯、128.2g/L葡萄糖,30℃、pH 6.5条件下反应6 h后,底物转化率达到100%,产物d.e.值大于99.5%。

t-butyl 6-cyano- （ 3R, 5R） -dihydroxyhexanoate, a key chiral building block for atorvastatin, was synthesized through asymmetric reduction of （R）-6-cyano-5-hydroxy-3-carbonylhexanoate catalyzed by carbonyl reductase coupled with glucose dehydrogenase. The optimized biocatalytic conditions were obtained ： （R） -6-cyano-5-hydroxy-3-carbonylhexanoate 147.0 g/L, glucose 128.2 g/L, cell loading 15.0 g/L, the pH 6.5, and 30 ℃. Under these conditions, （R） -6-cyano-5-hydroxy-3-carbonylhexanoate was completly converted for 6 h. Without exogenous addition of NADP （H） and with t-butyl 6-cyano-（ 3R, 5R）-dihydroxyhexanoate the d. e. value was over 99.5%.