Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol

Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks several β-blockers synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased use catalytic amount base. reason this was found to be reduced formation dimeric by-products compared higher concentration An overall reduction reagents and reaction time also obtained our previously reported data similar compounds. enantiomers chlorohydrin were kinetic resolution racemate transesterification reactions catalyzed Candida antarctica Lipase B (CALB). Optical rotations confirmed absolute configuration drugs. β-blocker (S)-practolol ((S)-N-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) with 96% excess (ee) from (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which produced 97% ee 27% yield. Racemic block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol pindolol 53% (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol 92% ee. 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a derivative carteolol 77% (R)-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one S-enantiomer 87% 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, drug carteolol, yield, R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. (S)-Carteolol low easily can improved.