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Exploration of the expeditious potential of Pseudomonas fluorescens lipase in the kinetic resolution of racemic intermediates and its validation through molecular docking
Author(s) -
Soni Surbhi,
Dwivedee Bharat P.,
Sharma Vishnu K.,
Patel Gopal,
Banerjee Uttam C.
Publication year - 2018
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22771
Subject(s) - chemistry , pseudomonas fluorescens , kinetic resolution , lipase , docking (animal) , pseudomonas , stereochemistry , enzyme , organic chemistry , enantioselective synthesis , catalysis , bacteria , medicine , genetics , nursing , biology
A profoundly time‐efficient chemoenzymatic method for the synthesis of ( S ) ‐ 3‐(4‐chlorophenoxy)propan‐1,2‐diol and ( S ) ‐ 1‐chloro‐3‐(2,5‐dichlorophenoxy)propan‐2‐ol, two important pharmaceutical intermediates, was successfully developed using Pseudomonas fluorescens lipase (PFL). Kinetic resolution was successfully achieved using vinyl acetate as acylating agent, toluene/hexane as solvent, and reaction temperature of 30°C giving high enantioselectivity and conversion. Under optimized condition, PFL demonstrated 50.2% conversion, enantiomeric excess of 95.0%, enantioselectivity (E = 153) in an optimum time of 1 hour and 50.3% conversion, enantiomeric excess of 95.2%, enantioselectivity (E = 161) in an optimum time of 3 hours, for the two racemic alcohols, respectively. Docking of the R‐ and S ‐enantiomers of the intermediates demonstrated stronger H‐bond interaction between the hydroxyl group of the R ‐enantiomer and the key binding residues of the catalytic site of the lipase, while the S ‐enantiomer demonstrated lesser interaction. Thus, docking study complemented the experimental outcome that PFL preferentially acylated the R form of the intermediates. The present study demonstrates a cost‐effective and expeditious biocatalytic process that can be applied in the enantiopure synthesis of pharmaceutical intermediates and drugs.