Asymmetric synthesis of 2,4,5-trisubstituted piperidines from sulfinimine-derived delta-amino beta-ketoesters. Formal synthesis of pseudodistomin B triacetate

J Org Chem. 2005 Jul 8;70(14):5413-9. doi: 10.1021/jo050373o.

Abstract

[reaction: see text] N-Sulfinyl delta-amino beta-ketoester enaminones, a new sulfinimine-derived chiral building block, undergoes, on hydrolysis in one pot, an intramolecular Michael addition followed by a retro-Michael-type elimination to give enantiopure 2,4,5-trisubstituted piperidines, a structural motif found in numerous biologically active alkaloids. This new chiral building block is readily prepared by treating N-sulfinyl delta-amino beta-ketoesters with dimethylformamide dimethyl acetal. This new protocol was illustrated with a concise formal asymmetric synthesis of marine alkaloid pseudodistomin B triacetate.

Publication types

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

MeSH terms

  • Acetals / chemistry
  • Alkaloids / chemistry*
  • Amines / chemistry
  • Cyclization
  • Dimethylformamide / chemistry
  • Esters / chemistry*
  • Imines / chemistry
  • Ketones / chemistry*
  • Models, Chemical
  • Piperidines / chemical synthesis*
  • Stereoisomerism
  • Sulfinic Acids / chemistry

Substances

  • Acetals
  • Alkaloids
  • Amines
  • Esters
  • Imines
  • Ketones
  • Piperidines
  • Sulfinic Acids
  • pseudodistomin B triacetate
  • Dimethylformamide