Delgado Francisco, Benítez Andrés, Gotopo Lourdes, Romero Angel H
Grupo de Química Orgánica Medicinal, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Laboratorio de Biología Redox de Tripanosomatidos, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Front Chem. 2025 Apr 1;13:1553975. doi: 10.3389/fchem.2025.1553975. eCollection 2025.
4-Aminoquinoline is an important scaffold due to its variety of applications in medicinal, synthetic organic, and industrial chemistry. It has gained great relevance for the development of selective and potent leishmanicidal agents targeting parasite mitochondria, agonists and antagonists of Toll-like receptors (TLRs), antimalarials, and anticancer agents. As a consequence of the importance of 4-aminoquinoline as leishmanicidal, the present mini-review article aims to give comprehensive information about the different synthetic alternatives for the synthesis of 4-aminoquinolines, including (i) reactions based on nucleophilic aromatic substitution via conventional heating, microwave, and ultrasound; (ii) one-pot metal-free or metal-catalyzed reactions of inter- and intramolecular cyclization/annulation; (iii) miscellaneous reactions including the dehydrogenative amination of dihydroquinolin-4()one and amination via Hartwig-Buchwald cross-coupling or rearrangement reactions.
4-氨基喹啉是一种重要的骨架结构，因其在药物化学、有机合成化学和工业化学中有着广泛的应用。它对于开发靶向寄生虫线粒体的选择性强效杀利什曼原虫剂、Toll样受体（TLRs）的激动剂和拮抗剂、抗疟药及抗癌药具有重要意义。鉴于4-氨基喹啉作为杀利什曼原虫剂的重要性，本篇综述文章旨在全面介绍4-氨基喹啉合成的不同合成方法，包括：（i）基于亲核芳香取代反应，通过常规加热、微波和超声进行的反应；（ii）分子间和分子内环化/环合的无金属或金属催化的一锅法反应；（iii）包括二氢喹啉-4(1H)-酮的脱氢胺化反应以及通过Hartwig-Buchwald交叉偶联或重排反应进行的胺化反应等杂项反应。
