Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-41296 Göteborg, Sweden.
Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, H-1117 Budapest, Hungary.
Org Biomol Chem. 2020 Mar 14;18(10):1957-1967. doi: 10.1039/d0ob00168f. Epub 2020 Feb 26.
1,4- and 1,5-Disubstituted triazole amino acid monomers have gained increasing interest among peptidic foldamers, as they are easily prepared via Cu- and Ru-catalyzed click reactions, with the potential for side chain variation. While the latter is key to their applicability, the synthesis and structural properties of the chiral mono- or disubstituted triazole amino acids have only been partially addressed. We here present the synthesis of all eight possible chiral derivatives of a triazole monomer prepared via a ruthenium-catalyzed azide alkyne cycloaddition (RuAAC). To evaluate the conformational properties of the individual building units, a systematic quantum chemical study was performed on all monomers, indicating their capacity to form several low energy conformers. This feature may be used to effect structural diversity when the monomers are inserted into various peptide sequences. We envisage that these results will facilitate new applications for these artificial oligomeric compounds in diverse areas, ranging from pharmaceutics to biotechnology.
1,4-和 1,5-取代的三唑氨基酸单体在肽折叠物中越来越受到关注，因为它们可以通过 Cu-和 Ru-催化的点击反应轻松制备，具有侧链变化的潜力。虽然后者是其适用性的关键，但手性单取代或双取代三唑氨基酸的合成和结构性质仅部分得到解决。我们在这里介绍了通过钌催化的叠氮化物-炔烃环加成反应（RuAAC）制备的一种三唑单体的所有八个可能的手性衍生物的合成。为了评估各个构建单元的构象性质，对所有单体进行了系统的量子化学研究，表明它们能够形成几种低能量构象。当单体插入到各种肽序列中时，该特性可用于实现结构多样性。我们设想这些结果将促进这些人工寡聚物化合物在从制药到生物技术等各个领域的新应用。
