Synthesis of 4-substituted-3-aminopiperidin-2-ones: application to the synthesis of a conformationally constrained tetrapeptide N-acetyl-Ser-Asp-Lys-Pro

J Org Chem. 2005 Jul 22;70(15):5946-53. doi: 10.1021/jo050736k.

Abstract

A new and practical synthetic strategy is developed for the synthesis of six-membered lactam-bridged dipeptides, 4-substituted-3-aminopiperidin-2-ones, featuring two key steps: (a) a diastereoselective addition of cuprate to (E)-alpha,beta-unsaturated ester (3) and (b) racemization-free reductive amination. On the basis of this methodology, conformationally constrained tetrapeptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) (2) has been successfully synthesized from 3-amino-4-vinylpiperidin-2-one (22).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Bridged-Ring Compounds / chemistry*
  • Lactams / chemistry*
  • Models, Chemical
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology
  • Oxidation-Reduction
  • Piperidones / chemical synthesis*
  • Piperidones / pharmacology
  • Stereoisomerism

Substances

  • 3-aminopiperidine-2-one
  • Bridged-Ring Compounds
  • Lactams
  • Oligopeptides
  • Piperidones
  • goralatide