Synthesis 2022; 54(13): 3025-3046
DOI: 10.1055/s-0041-1737396
paper

Enantiopure β3-Trifluoromethyl-β3-homoalanine Derivatives: Coupling with Boc-Protected Amino Acids and Conformational Studies of Peptides in Solid State

Nathalie Saraiva Rosa
,
Fabienne Grellepois
We gratefully thank the Agence Nationale de la Recherche for financial support (TFM4Asym project ANR JCJC: ANR-13-JS07-0011-01).


Abstract

The use of enantiopure β3-trifluoromethyl-β3-alkyl β-amino acids for the design of peptides would contribute to drastically enhance peptide stability in vivo. Moreover, the steric hindrance generated by the substituents on the tetrasubstituted carbon adjacent to the nitrogen function coupled to the electron-withdrawing effect of the trifluoromethyl group is more likely to influence the 3D conformation of the peptide. Herein, we describe a short, scalable and robust method to synthesize N- and/or C-protected enantiopure (R)- and (S)-β3-trifluoromethyl-β3-methyl β-amino acid derivatives and liquid-phase coupling methods suitable for incorporation of Boc-protected amino acids into short α/β- and β-peptides. Conformational studies of some of these original peptides via X-ray diffraction analysis highlighted intraresidue C6 hydrogen bonds within trifluoromethylated amino acids.

Supporting Information



Publikationsverlauf

Eingereicht: 22. November 2021

Angenommen nach Revision: 16. Februar 2022

Artikel online veröffentlicht:
06. April 2022

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