Continuous-flow protocol for the synthesis of enantiomerically pure intermediates of anti epilepsy and anti tuberculosis active pharmaceutical ingredients

Org Biomol Chem. 2019 Feb 6;17(6):1552-1557. doi: 10.1039/c8ob03088j.

Abstract

Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks. In this work we developed two different strategies for the synthesis of intermediates used on the synthesis of levetiracetam/brivaracetam and ethambutol. The results obtained show that methionine methyl ester can be continuously converted to the desired ethambutol intermediate by RANEY® Nickel dessulfurization/reduction strategy whereas levetiracetam/brivaracetam intermediates could be synthesized by both RANEY® Nickel (without H2) and Pd/C-H2 approach or by photochemical desulfurization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / chemistry
  • Anticonvulsants / pharmacology*
  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Chemistry Techniques, Synthetic
  • Ethambutol / chemical synthesis
  • Ethambutol / chemistry
  • Ethambutol / pharmacology
  • Levetiracetam / chemical synthesis
  • Levetiracetam / chemistry
  • Levetiracetam / pharmacology
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / chemistry
  • Pyrrolidinones / pharmacology
  • Stereoisomerism
  • Sulfur / chemistry

Substances

  • Anticonvulsants
  • Antitubercular Agents
  • Pyrrolidinones
  • Levetiracetam
  • Sulfur
  • Ethambutol
  • brivaracetam