On the Use of Orthoformates as an Efficient Approach to Enhance the Enzymatic Enantioselective Synthesis of (S)-Ibuprofen

In this paper, we describe the effectiveness of the combination between an organic solvent system mixture with orthoformates with different chain sizes from one to four carbon atoms. These orthoesters have been used as a water trapper/alcohol releaser molecule to reach a notable improvement in enantioselectivity and enantiomeric excess of our target compound, (S)-2-(4-isobutylphenyl)propanoic acid (ibuprofen eutomer), during the enzymatic kinetic resolution of rac-ibuprofen using immobilized lipase B of Candida antarctica as a biocatalyst. At the same time, one of the great problems of biocatalysis in organic media has been solved by eliminating excess water in the medium that allows the reversibility of the reaction. Following the optimization of the reaction conditions, an increase in enantiomeric excess and enantioselectivity was reached by using these acyl donors in the presence of a cosolvent.

Automated summary

In this paper, the authors study the combination between different chain sizes of orthoesters and an organic solvent mixture. These orthoesters act as water trappers and alcohol releasers during the enzymatic kinetic resolution of rac-ibuprofen. By using these orthoesters in the presence of a cosolvent, an improvement in enantioselectivity and enantiomeric excess of the target compound is achieved.