Ketoreductase RasADH-E189D and application thereof
By using ketone reductase to catalyze the asymmetric reduction reaction of aryl-substituted alkenyl 3,5-dicarbonyl esters, the problem of the difficulty in efficiently preparing chiral β-hydroxy esters in the existing technology has been solved, achieving a biocatalytic effect with high selectivity and high conversion rate, and successfully synthesizing pitavastatin intermediates.
Patent Information
- Application Number
- CN202610620943.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-08
- Publication Date
- 2026-06-02
- Estimated Expiration
- 2046-05-08
AI Technical Summary
Existing methods are insufficient to efficiently achieve highly selective asymmetric reduction of aryl-substituted alkenyl 3,5-dicarbonyl esters to prepare chiral β-hydroxy esters without pre-reduction, protection, or pre-functionalization of the substrate.
A biocatalytic platform was constructed to prepare high-purity chiral aryl-substituted alkenyl β-hydroxy esters by using ketone reductases RasADH, RasADH-E189D, KmCR2, SSCR-QA, or SSCR-QA to catalyze the asymmetric reduction reaction of aryl-substituted alkenyl 3,5-dicarbonyl esters.
Highly selective asymmetric reduction of aryl-substituted alkenyl 3,5-dicarbonyl esters was achieved with a conversion rate of 89%-99% and an enantioselectivity of 93%-99%. Key intermediates of pitavastatin were also successfully prepared, exhibiting good diastereoselectivity.