A practical and facile synthesis of azetidine derivatives for oral carbapenem, L-084

Chem Pharm Bull (Tokyo). 2006 Oct;54(10):1408-11. doi: 10.1248/cpb.54.1408.

Abstract

An orally active carbapenem L-084, which exhibits high bioavailability in humans, has a 1-(1,3-thiazolin-2-yl)azetidin-3-ylthio moiety at the C-2 position of the 1beta-methylcarbapenem skeleton. We established a practical and cost-effective synthesis of 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine (1) for further scale-up production of L-084. This synthesis method entails an industry-oriented reaction of azetidine ring-closure to yield N-benzyl-3-hydroxyazetidine (16), which is eventually converted to 1 via key intermediates, Bunte salts 19 and 20.

MeSH terms

  • Administration, Oral
  • Azetidines / chemical synthesis*
  • Azetidines / chemistry
  • Carbapenems / administration & dosage
  • Carbapenems / chemical synthesis*
  • Carbapenems / chemistry
  • Drug Industry
  • Humans
  • Molecular Structure
  • Stereoisomerism
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry

Substances

  • 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine
  • Azetidines
  • Carbapenems
  • Thiazoles
  • azetidine
  • L 084