1,5-Disubstituted 1,2,3-Triazole-Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

Kracker O., Gora J., Krzciuk-Gula J., Marion A., Neumann B., Stammler H., ...More

CHEMISTRY-A EUROPEAN JOURNAL, vol.24, no.4, pp.953-961, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 4
  • Publication Date: 2018
  • Doi Number: 10.1002/chem.201704583
  • Journal Name: CHEMISTRY-A EUROPEAN JOURNAL
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.953-961
  • Keywords: conformational analysis, foldamers, peptidomimetics, ruthenium, triazoles, AZIDE-ALKYNE CYCLOADDITION, CLICK CHEMISTRY, TERT-BUTANESULFINAMIDE, TERMINAL ALKYNES, SOLID-PHASE, STEREOSELECTIVE-SYNTHESIS, GROWING APPLICATIONS, ASYMMETRIC-SYNTHESIS, TRIAZOLE OLIGOMERS, PEPTIDE-SYNTHESIS
  • Middle East Technical University Affiliated: No

Abstract

Peptidotriazolamers are hybrid foldamers combining features of peptides and triazolamers-repetitive peptidomimetic structures with triazoles replacing peptide bonds. We report on the synthesis of a new class of peptidomimetics, containing 1,5-disubstituted 1,2,3-triazoles in an alternating fashion with amide bonds and the analysis of their conformation in solid state and solution. Homo-or heterochiral peptidotriazolamers were obtained from enantiomerically pure propargylamines with stereogenic centers in the prop-argylic position and alpha-azido esters by ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) under microwave conditions in high yields. With such building blocks the peptidotriazolamers are readily available by solution phase synthesis. While the conformation of the homochiral peptidotriazolamer Boc-Ala[5Tz] Phe-Val[5Tz] Ala-Leu[5Tz] Val-OBzl resembles that of a beta VIa1 turn, the heterochiral peptidotriazolamer Boc- D-Ala[5Tz] Phe-D-Val[5Tz] Ala-d-Leu[5Tz] Val-OBzl adopts a polyproline-like repetitive structure.