Enantioselective hydrolysis of 3-hydroxy-1,4-benzodiazepin-2-one esters by pig liver microsomes

• The S-enantiomers of the 3-hydroxy-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one esters were obtained (ees >97%).
• S-enantiomers were 1.4–2.1 times more potent ligands of CBR than the corresponding racemates.
• Pig liver microsomal fraction was immobilized in calcium alginate beads.
• Obtained biocatalyst has been applied for the enantioselective hydrolysis of the esters for 12 cycles of use.

The method of enantioselective hydrolysis of 3-hydroxy-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one esters using pig liver microsomal fraction was developed. The S-enantiomers of three substrates were obtained with ees >97% and yields 44–49%, their absolute configurations were determined by X-ray crystallography. It was shown, that the S-enantiomers of 3-hydroxy-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one esters were 1.4–2.1 times more potent ligands of CBR than the corresponding racemates. Pig liver microsomal fraction was immobilized in calcium alginate beads. It was shown, that immobilized preparation has three times greater thermal stability at 50 °C compared to the free microsomal fraction. Enantioselective hydrolysis of 1-methyl-3-acetoxy-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one using immobilized microsomal fraction was conducted for 12 cycles of use without loss of the esterase activity.