Synthesis of ( S)-3-Amino-4-(difluoromethylenyl)-cyclopent-1-ene-1-carboxylic Acid (OV329), a Potent Inactivator of γ-Aminobutyric Acid Aminotransferase

Org Lett. 2018 Aug 3;20(15):4589-4592. doi: 10.1021/acs.orglett.8b01872. Epub 2018 Jul 16.

Abstract

( S)-3-Amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (OV329, 1) is being developed for the treatment of epilepsy and addiction. The previous 14-step synthesis of OV329 was low yielding, involved an unselective α-elimination to form the cyclopentene, required the use of tert-butyllithium, and produced toxic selenium byproducts in the penultimate step. A new synthesis, which avoids the aforementioned issues, was carried out on large scale, reducing the step count from 14 to 9 steps and increasing the overall yield from 3.7% to 8.1%.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 4-Aminobutyrate Transaminase / antagonists & inhibitors*
  • Cyclopentanes / chemistry*
  • Enzyme Inhibitors / chemical synthesis*
  • Molecular Structure
  • Organometallic Compounds / chemistry
  • Phenylacetates / chemistry
  • Selenium Compounds / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship
  • Transaminases / antagonists & inhibitors*

Substances

  • Cyclopentanes
  • Enzyme Inhibitors
  • Organometallic Compounds
  • Phenylacetates
  • Selenium Compounds
  • butyllithium
  • cyclodrine
  • Transaminases
  • 4-Aminobutyrate Transaminase