酮还原酶在罗苏伐他汀制备中的应用

On Application of Ketoreductase in Production of Rosuvastatin

将酮还原酶应用于降血脂药罗苏伐他汀的制备.通过高通量筛选,酮还原酶KRED-4可催化罗苏伐他汀乙酯的制备反应.经过反应条件的初步优化后,确定了该酶催化反应的最适温度为25~35℃、最适pH值为6.0、初始底物浓度1g/L和酶浓度2g/L.在最优条件下,可将底物1完全转化为产物2罗苏伐他汀乙酯,产物的构型完全正确,且de〉99.9%,为建立罗苏伐他汀制备的绿色工艺提供了新的思路.

Ketoreductasehas been used in a synthesis of the lipid‐lowering agent Rosuvastatin .By high‐throughput screening ,KRED‐4has beenpicked up to prepare Rosuvastatin ethyl ester .After a preliminary optimization ,the enzymatic reactiontemperature 25℃ ~35℃ ,pH6 .0 ,initial substrate concentration1g/L and enzyme concentration 2g/Lhave been determined .In optimal conditions ,the substrate can be com‐pletely transformed into the product of Rosuvastatin ethyl ester .The configuration of the product is entire‐ly correct ,and the de〉99 .9% ,providinga new idea for the green technology of Rosuvastatin prepared .