Study on the different replacing groups of trans-paroxol for enzymatic resolution using molecular simulations

Abstract

Trans-paroxol is an important key intermediate for paroxetine synthesis. Four different replacing groups of trans-paroxol on the kinetic resolution were studied to illuminate the mechanism of enzymatic catalysis using molecular simulations. Hydrogen bonds, hydrophobic interactions and the protein structure were analysed for enzyme-substrate complex. Results indicated that the formation of hydrogen bond, hydrophobic interactions and the distribution of substrate conformation in active site were the major forces which resulted in the diversity of enzymatic resolution. Electrostatic interactions and the stability of complex also played an important role in this reaction. This study will be quite useful for understanding the mechanism of enzymatic resolution and guiding to design the appropriate substrate for paroxetine synthesis.