Pyrrolidine ring puckering and prolyl amide bond configurations of 2-methyl-allo-hydroxyproline-based dipeptides

Org Biomol Chem. 2019 May 8;17(18):4460-4464. doi: 10.1039/c9ob00150f.

Abstract

An expeditious method for the synthesis of homo and heterochiral dipeptides containing l-alanine and d/l 2-methyl allo-hydroxyl prolines was developed using direct aminolysis of bicyclic lactones derived from d/l alanine. The impact of C-2 methylation and its spatial orientation on the pyrrolidine ring puckering and prolyl amide bond configuration was ascertained by solution NMR studies. The present studies reveal that C-2 methylation causes the prolyl amide bond to exist exclusively in the trans geometry in both homo- and heterochiral dipeptides. However, the spatial orientation of the C-2 methyl group and its i + 2 position in appropriately capped model dipeptides may nucleate into a turn like structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Dipeptides / chemical synthesis
  • Dipeptides / chemistry*
  • Hydroxyproline / chemistry*
  • Magnetic Resonance Spectroscopy
  • Molecular Dynamics Simulation
  • Protein Conformation
  • Pyrrolidines / chemistry*
  • Stereoisomerism

Substances

  • Amides
  • Dipeptides
  • Pyrrolidines
  • Hydroxyproline