Molecular modeling of the lipase-catalyzed hydrolysis of acetoxymethyl(i-propoxy)phenylphosphine oxide and its P-borane analogue.
The molecular modeling of the CAL-B-promoted hydrolysis reactions of acetoxymethyl(i-propoxy)phenylphosphine oxide and its P-borane analogue, acetoxymethyl(i-propoxy)-phenylphosphine P-borane, confirms that the reactions proceed with the same stereochemistry and in both cases the (S)-enantiomers are preferentially transformed by the enzyme. Molecular mechanics calculations show that the main reason for the particular stereoselectivity of the substrates is the steric effect of the phenyl group which causes a remarkable hindrance when placed inside the active site. The replacement of the oxygen by a borane group at the phosphorus stereogenic center does not nullify the stereorecognition by the enzyme, although for the P-borane a lower stereoselectivity is observed. The latter is explained in terms of a smaller energy difference between complexes of CAL-B and particular enantiomers of the P-borane in comparison with those of the phosphine oxide, resulting from the steric effect of the BH₃ group. The results helped to revise the previously published erroneous conclusions concerning absolute configuration of the phosphine-borane complex.
Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland.
Grzegorz
G
Krasiński
Marek
M
Cypryk
Małgorzata
M
Kwiatkowska
Marian
M
Mikołajczyk
Piotr
P
Kiełbasiński
D055162:Biocatalysis; D001880:Boranes / Q000737:chemistry*; D020134:Catalytic Domain; D006540:Herbicides / Q000138:chemical synthesis; D006868:Hydrolysis; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D010087:Oxides / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013816:Thermodynamics
D001880:Boranes; D006540:Herbicides; D010087:Oxides; D010720:Phosphines; D008049:Lipase