Institute of Pharmaceutical Chemistry and Research Group for Stereochemistry, Hungarian Academy of Sciences, University of Szeged, H-6720, Szeged, Eötvös u. 6, Hungary; Institute of Pharmaceutical Chemistry, University of Szeged, Interdisciplinary Excellence Center, H-6720, Szeged, Eötvös u. 6, Hungary.
Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725, Szeged, Hungary.
Eur J Med Chem. 2022 Jul 5;237:114391. doi: 10.1016/j.ejmech.2022.114391. Epub 2022 Apr 18.
Starting from naphthols and morpholine and using ethyl glyoxylate as the aldehyde component in the modified Mannich reaction, new aminonaphthol derivatives substituted with 2- and 1-naphthol were synthesised. The stabilization of precursor bifunctional compounds via partially aromatic ortho-quinone methide intermediate was tested with different cyclic imines in [4 + 2] cycloaddition. Based on H NMR analysis, in the case of new α-amino acid esters the formation of a single product has been assumed. The NOE spectrum proved that the relative configuration of the newly formed stereogenic centres was trans. The compounds have also been tested in bacteria in order to reduce or reverse antibiotic resistance. Compounds 13 and 14 could inhibit the efflux pump system in susceptible and methicillin-resistant Staphylococcus aureus strains.
从萘酚和吗啉开始，使用乙二醛作为改良曼尼希反应的醛组分，合成了取代 2-和 1-萘酚的新型氨萘酚衍生物。通过部分芳构化邻醌甲叉中间体对前体双功能化合物进行了稳定性测试，在[4+2]环加成反应中使用了不同的环状亚胺。根据 1H NMR 分析，在新的α-氨基酸酯的情况下，假定形成了单一产物。NOE 谱证明了新形成的立体中心的相对构型为反式。还在细菌中测试了这些化合物，以降低或逆转抗生素耐药性。化合物 13 和 14 可以抑制敏感和耐甲氧西林金黄色葡萄球菌菌株中的外排泵系统。
