Solid-phase SN2 macrocyclization reactions to form beta-turn mimics

Org Lett. 1999 Jul 15;1(1):121-4. doi: 10.1021/ol990597r.

Abstract

[formula: see text] Efficient solid-phase SN2 macrocyclization reactions were sought to facilitate preparations of focused libraries of beta-turn mimetics. A very efficient, but undesired, cyclization reaction to give five-membered ring lactams 4 was identified in attempts to use O-nucleophiles. Subsequent studies focused exclusively on S-nucleophiles. These reactions gave the desired macrocyclization products 1 in high purities and good overall yields. Conformational analyses of illustrative macrocyclization products 1 via NMR, CD, and molecular simulations showed that they seem to sample both type I and type II beta-turn conformations in solution. CD studies indicate a curious relationship between the preferred conformation and the amino acids encapsulated in the macrocycles.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Circular Dichroism
  • Cyclization
  • Molecular Mimicry
  • Peptides / chemistry*
  • Protein Conformation
  • Proteins / chemistry
  • Serine / chemistry
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • beta-Lactams / chemical synthesis*

Substances

  • Peptides
  • Proteins
  • beta-Lactams
  • Serine