Privileged structures as peptide backbone constraints: polymer-supported stereoselective synthesis of benzimidazolinopiperazinone peptides

ACS Comb Sci. 2014 Jul 14;16(7):359-66. doi: 10.1021/co500023k. Epub 2014 Apr 29.

Abstract

A molecular scaffold comprising a privileged structure was designed and synthesized to serve as a peptide backbone conformational constraint. The synthesis of highly functionalized 2,3,10,10a-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-4(1H)-ones on a solid-phase support was performed via a tandem N-acyl-N-aryliminium ion cyclization-nucleophilic addition reaction. The synthesis proceeded with full stereocontrol of the newly formed stereogenic center. Conventional and microwave-assisted syntheses were compared with respect to efficiency and the optical integrity of the target compounds. Significant epimerization was observed during acylation with (S)- and (R)-2-bromopropionic acids under microwave conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Microwaves
  • Molecular Conformation
  • Peptides / chemical synthesis*
  • Peptides / chemistry*
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Polymers / chemistry*
  • Stereoisomerism

Substances

  • Benzimidazoles
  • Peptides
  • Piperazines
  • Polymers