Spirolactams as conformationally restricted pseudopeptides: synthesis and conformational analysis

J Org Chem. 2002 Nov 1;67(22):7587-99. doi: 10.1021/jo025999i.

Abstract

The synthesis of 1-(tert-butoxycarbonyl)-7-[1-(tert-butoxycarbonyl)-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.5]decanes (S,S)-1a and (S,R)-1b is described. Derivatives 17a,b and 19a are prepared for use in peptide synthesis as constrained surrogates of the Pro-Leu and Gly-Leu dipeptides. The Ac-[Gly-Leu]-Met-NH(2) derivatives (S,S,S)-2a and (S,R,S)-2b, with the tripeptidic C-terminal region present in tachykinins, are also synthesized. Conformational analyses of these tripetide analogues by NMR experiments and molecular modeling calculations show that both (S,S,S)-2a and (S,R,S)-2b epimers are gamma-turn/distorted type II beta-turn mimetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hydrogen Bonding
  • Lactams / chemistry*
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Molecular Structure
  • Peptides / chemical synthesis*
  • Peptides / chemistry*
  • Stereoisomerism
  • Temperature
  • Thermodynamics

Substances

  • Lactams
  • Peptides