Theoretical DFT study of stereoselective hydrolysis of enantiomers of naproxen

Abstract

Ester hydrolysis is a common and important reaction in organic chemistry. It is catalyzed by acid or base. This phenomenon becomes very interesting when it attains enantioselectivity. Its most common example is the enantioselective hydrolysis of the S-naproxen ester. When the hydrolysis of R/S-naproxen ester is performed, only the S-naproxen ester takes part in the hydrolysis, but the R-naproxen ester does not. Because of this, the hydrolysis of R/S naproxen ester is used to gain pharmaceutically and biologically active S-naproxen. The data in the literature describe why the hydrolysis of only the S-naproxen ester is possible, while that of the R-naproxen ester is not. Furthermore, another notable question is the acid-catalyzed nature alone, while simple ester hydrolysis is an acid-base-catalyzed phenomenon. The theoretical DFT study answers these complicated questions. In the presented article, different parameters of the ester group (-COO-) constituents of the simple ester as well as the R/S naproxen ester in water were theoretically studied. These parameters were the same between the S-naproxen ester and the simple ester after DFT calculation in water. On the other hand, the R-naproxen ester did not show similarities to that of simple ester in water.