Lipase mediated enzymatic kinetic resolution of phenylethyl halohydrins acetates: A case of study and rationalization

• Published in: Molecular Catalysis
• Main Authors: Thiago de Sousa Fonseca, Kimberly Benedetti Vega, Marcos Reinaldo da Silva, Maria da Conceição Ferreira de Oliveira, Telma Leda Gomes de Lemosa, Martina Letizia Contenteb, Francesco Molinari, Marco Cespugli, Sara Fortuna, Lucia Gardossi, Marcos Carlos de Mattos
• Other Authors: de Sousa Fonseca, Thiago, Benedetti Vega, Kimberly, Reinaldo da Silva, Marco, da Conceição Ferreira de Oliveira, Maria, Leda Gomes de Lemosa, Telma, Letizia Contenteb, Martina, Molinari, Francesco, Cespugli, Marco, Fortuna, Sara, Gardossi, Lucia, Carlos de Mattos, Marcos
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2020
• Subjects: Biocatalysis; Enzymatic kinetic resolution; Lipases; Halohydrins; Molecular docking; Antarc*; Antarctica
• Online Access: http://hdl.handle.net/11368/2957718; https://doi.org/10.1016/j.mcat.2020.110819

Racemic phenylethyl halohydrins acetates containing several groups attached to the aromatic ring were resolved via hydrolysis reaction in the presence of lipase B from Candida antarctica (Novozym® 435). In all cases, the kinetic resolution was highly selective (E>200) leading to the corresponding (S)-β-halohydrin with ee>99 %. However, the time required for an ideal 50 % conversion ranged from 15 min for 2,4-dichlorophenyl chlorohydrin acetate to 216 h for 2-chlorophenyl bromohydrin acetate. Six chlorohydrins and five bromohydrins were evaluated, the latter being less reactive. For the β-brominated substrates, steric hindrance on the aromatic ring played a crucial role, which was not observed for the β-chlorinated derivatives. To shed light on the different reaction rates, docking studies were carried out with all the substrates using MD simulations. The computational data obtained for the β-brominated substrates, based on the parameters analysed such as NAC (near attack conformation), distance between Ser-O and carbonyl-C and oxyanion site stabilization were in agreement with the experimental results. On the other hand, the data obtained for β-chlorinated substrates suggested that physical aspects such as high hydrophobicity or induced change in the conformation of the enzymatic active site are more relevant aspects when compared to steric hindrance effects.