Asymmetric Total Synthesis of Meptazinol

J Org Chem. 2022 May 6;87(9):6410-6417. doi: 10.1021/acs.joc.2c00272. Epub 2022 Apr 12.

Abstract

The first enantioselective synthesis of (S)-meptazinol in 14 steps from commercially available ethyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate, being widely used in racemic form for pain treatment, and, en route, the formal synthesis of two anti-Alzheimer's agents are reported. A novel ring expansion of 2-azabicyclo[4.1.0]heptanes, readily available via the stereoselective cyclopropanation of 1,2,3,4-tetrahydropyridine-4-ols, provides an effective entry to 3,3-disubstituted azepanes that represent the core for a variety of approved drugs.

MeSH terms

  • Carboxylic Acids
  • Meptazinol*
  • Stereoisomerism

Substances

  • Carboxylic Acids
  • Meptazinol