δ-Valerolactamic Quaternary Amino Acid Derivatives : Enantiodivergent Synthesis and Evidence for Stereodifferentiated β-Turn-Inducing Properties
| Autor: | Sandrine Py, Arnaud Martel, Sullivan Bricaud, Romain Ligny, Sopa Chewchanwuttiwong, Mathieu Y. Laurent, Rawan Hadade, Corentin Jacquemmoz, Jérôme Lhoste, Gilles Dujardin, X. M. Zhang |
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| Přispěvatelé: | Institut des Molécules et Matériaux du Mans (IMMM), Le Mans Université (UM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Prince of Songkla University (PSU), Département de Chimie Moléculaire - Synthèse Et Réactivité en Chimie Organique (DCM - SeRCO), Département de Chimie Moléculaire (DCM), Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular chemistry.chemical_classification Magnetic Resonance Spectroscopy 010405 organic chemistry Peptidomimetic Chemistry Stereochemistry [CHIM.ORGA]Chemical Sciences/Organic chemistry In silico Organic Chemistry Solid-state Sequence (biology) 010402 general chemistry 01 natural sciences Protein Structure Secondary 0104 chemical sciences Amino acid Enantiopure drug X-Ray Diffraction Side chain Amino Acids |
| Zdroj: | Journal of Organic Chemistry Journal of Organic Chemistry, American Chemical Society, 2021, 86 (12), pp.8041-8055. ⟨10.1021/acs.joc.1c00456⟩ |
| ISSN: | 0022-3263 1520-6904 |
| DOI: | 10.1021/acs.joc.1c00456⟩ |
| Popis: | International audience; Enantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics |
| Databáze: | OpenAIRE |
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