Synthesis of the antistroke drug lubeluzole and its enantiomer. Lipase-catalyzed resolution of chiral building block

Chirality. 2001;13(3):135-9. doi: 10.1002/1520-636X(2001)13:3<135::AID-CHIR1010>3.0.CO;2-D.

Abstract

1-Chloro-3-(3,4-difluorophenoxy)-2-propanol was kinetically resolved by lipase-catalyzed esterification with vinyl butanoate in organic medium to yield the (S)-butanoate and the (R)-alcohol as the remaining substrate. In an enantioconvergent synthesis the mixture was subject to Mitsunobu esterification in one pot which converted the (R)-alcohol to the (S)-ester. The (S)-butanoate was hydrolyzed by lipase catalysis to give (S)-1-chloro-3-(3,4-difluorophenoxy)-2-propanol. The two enantiopure chiral building blocks were used for synthesis of Lubeluzole and its enantiomer respectively.

MeSH terms

  • Cardiovascular Agents / chemical synthesis*
  • Catalysis
  • Lipase / chemistry*
  • Piperidines / chemical synthesis*
  • Propanols / chemistry
  • Propanols / isolation & purification
  • Stereoisomerism
  • Substrate Specificity
  • Thiazoles / chemical synthesis*

Substances

  • Cardiovascular Agents
  • Piperidines
  • Propanols
  • Thiazoles
  • Lipase
  • lubeluzole