Design of Pseudodiproline Dimers as Mimetics of Pro-Pro Units: Stereocontrolled Synthesis, Configurational Relevance, and Structural Properties

J Org Chem. 2021 Dec 3;86(23):16834-16847. doi: 10.1021/acs.joc.1c02061. Epub 2021 Nov 8.

Abstract

Stereocontrolled methods are described for the synthesis of hitherto unreported pseudodiproline dimers in which a cyclopentane carboxylic acid is linked to a pyrrolidine residue by a stereochemically defined hydroxymethylene tether. These proline-cyclopentane (Pro-Cyp) dimers have interesting structural characteristics as seen in their X-ray crystal structures as well as their nuclear magnetic resonance (NMR) spectra in CDCl3. They can be considered to be novel Pro-Pro mimetics, which can be used to replace natural diproline sequences with potential applications in medicinal chemistry. They also represent a new concept in the peptidomimetic design of chimeric proline-based amino acids as carbocyclic hydroxyethylene isosteres of inhibitor molecules, in which the stereodefined bridging hydroxyl group can simulate a tetrahedral intermediate in an enzyme complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dipeptides*
  • Magnetic Resonance Spectroscopy
  • Peptidomimetics*
  • Proline

Substances

  • Dipeptides
  • Peptidomimetics
  • prolyl-proline
  • Proline