Continuous flow method for preparing (R)-3-hydroxy-5-hexenoate

A continuous-flow method for preparing (R)-3-hydroxy-5-hexenoate of formula (I) using a micro reaction system, the micro reaction system comprising a microchannel reactor,

• the method comprising:
• (1) co-immobilizing a carbonyl reductase and an isopropanol dehydrogenase onto an inert solid medium to prepare a carbonyl reductase/isopropanol dehydrogenase co-immobilized catalyst;
• and filling the microchannel reactor with the co-immobilized catalyst;
• (2) pumping a substrate solution containing 3-carbonyl-5-hexenoate of formula (II) into the microchannel reactor filled with the carbonyl reductase/isopropanol dehydrogenase co-immobilized catalyst prepared in step (1) to perform an asymmetric carbonyl reduction reaction;
• and
• (3) collecting the reaction mixture flowing out of the microchannel reactor followed by separation and purification to obtain a target product (R)-3-hydroxy-5-hexenoate;
• wherein R is linear or branched C1-C8 alkyl group, linear or branched C3-C8 cycloalkyl group, monosubstituted or polysubstituted aryl group, or monosubstituted or polysubstituted aralkyl group;
• wherein an amino acid sequence of the carbonyl reductase is SEQ ID NO:
• 1;
• an amino acid sequence of the isopropanol dehydrogenase is SEQ ID NO:
• 2;
• and
• wherein the yield of the product (R)-3-hydroxy-5-hexenoate is increased from 80% to more than 95% compared to a method using a batch reactor.