A Convenient Synthesis of (16 S,20 S)-3β-hydroxy-5α-pregnane-20,16-carbolactam and its N-alkyl Derivatives

Molecules. 2020 May 20;25(10):2377. doi: 10.3390/molecules25102377.

Abstract

A concise synthesis of (16S,20S)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route consisted of the lactone ring-opening with aminoalane reagent followed by PDC or Dess-Martin oxidation. The oxo-amide obtained was subjected to cyclization with Et3SiH/TFA or Et3SiH/Bi(TfO)3. Alternately, the lactone was converted first to the oxo-acid, which was then subjected to the microwave-assisted reductive amination. N-Alkyl derivatives were also obtained in a similar way.

Keywords: lactams; reductive amination; spirostane degradation; steroids.

MeSH terms

  • Cyclization*
  • Lactones / chemical synthesis*
  • Lactones / chemistry
  • Oxidation-Reduction
  • Pregnanes / chemical synthesis*
  • Pregnanes / chemistry

Substances

  • Lactones
  • Pregnanes