A post-elongation strategy for the introduction of guanidinium units in the main chain of helical oligourea foldamers

Karolina Pulka-Ziach (1, 2) , Stéphanie Antunes (2) , Camille Perdriau (2) , Brice Kauffmann (3) , Morgane Pasco (2) , Céline Douat (2) , Gilles Guichard (2)

1 Faculty of Chemistry [Warsaw]
2 CBMN - Chimie et Biologie des Membranes et des Nanoobjets
3 Institut Européen de Chimie et de Biologie

The synthesis of hybrid urea-based foldamers containing isosteric guanidinium linkages at selected positions in the sequence is described. We used a postelongation approach whereby the guanidinium moiety is introduced by direct transformation of a parent oligo(urea/thiourea) foldamer precursor. The method involves activation of the thiourea by treatment with methyl iodide and subsequent reaction with amines. To avoid undesired cyclization with the preceding urea moiety, resulting in heterocyclic guanidinium formation in the main chain, the urea unit preceding the thiourea unit in the sequence was replaced by an isoatomic and isostructural gamma-amino acid. The approach was extended to solid-phase techniques to accelerate the synthesis of longer and more functionalized sequences. Under optimized conditions, an octamer hybrid oligomer incorporating a central guanidinium linkage was obtained in good overall yield and purity. This work also reports data related to the structural consequences of urea by guanidinium replacements in solution and reveals that helical folding is substantially reduced in oligomers containing a guanidinium group.

Mots clés: Mixtures; Solvents; Guanidine; Urea; Oligomers

Domaines: Chimie organique; Matériaux

Karolina Pulka-Ziach, Stéphanie Antunes, Camille Perdriau, Brice Kauffmann, Morgane Pasco, et al.. A post-elongation strategy for the introduction of guanidinium units in the main chain of helical oligourea foldamers. Journal of Organic Chemistry, 2018, 83 (5), pp.2530-2541. ⟨10.1021/acs.joc.7b01895⟩. ⟨hal-02345248⟩