Mekheimer Ramadan A, Allam Samar M R, Al-Sheikh Mariam A, Medrasi Hanadi Y, Abd-Elmonem Mohamed, Sadek Kamal U
Department of Chemistry, Faculty of Science, Minia University Minia 61519 Egypt
Faculty of Physical Therapy, Deraya University Minia Egypt.
RSC Adv. 2025 Apr 22;15(16):12494-12527. doi: 10.1039/d5ra00779h. eCollection 2025 Apr 16.
Among quinoline-fused heterocycles, tricyclic pyrimidoquinoline nuclei have received considerable attention from synthetic chemists and medicinal and materials scientists over many years because they occur commonly in various biologically important natural products and potent drugs that exhibit anticancer, antibacterial, anti-inflammatory, antilipidemic, antioxidant and antimalarial activities. This study will be beneficial for medicinal chemists in the field of drug discovery to synthesize new fused tricyclic pyrimidoquinolines as potent therapeutic agents. This review provides a comprehensive compilation of the methodologies developed for the synthesis of all six known types of pyrimidoquinolines reported thus far. This article includes synthesis solvent-free reactions, Vilsmeier-Haack reaction, Lewis and Brønsted acid catalysis, Pictet-Spengler reaction, the use of metal oxide nanoparticles as a green catalyst, multicomponent reactions (MCR), the use of l-proline as an environmentally friendly organocatalyst, aza-Wittig reaction, the use of β-cyclodextrin (β-CD) as a supramolecular catalyst, ultrasound irradiation, microwave-assisted reaction and ultraviolet light (UV) irradiation. To the best of our knowledge, this is the first review that focuses on the synthesis of all six types of pyrimidoquinolines along with mechanistic aspects. Some medicinal applications are also mentioned.
在喹啉稠合杂环中，三环嘧啶并喹啉核多年来一直受到合成化学家、药物和材料科学家的广泛关注，因为它们普遍存在于各种具有重要生物学意义的天然产物和具有抗癌、抗菌、抗炎、抗血脂、抗氧化和抗疟活性的强效药物中。这项研究将有助于药物发现领域的药物化学家合成新型稠合三环嘧啶并喹啉作为强效治疗剂。本综述全面汇编了迄今为止报道的用于合成所有六种已知类型嘧啶并喹啉的方法。本文包括无溶剂反应合成、Vilsmeier-Haack反应、路易斯酸和布朗斯特酸催化、Pictet-Spengler反应、使用金属氧化物纳米颗粒作为绿色催化剂、多组分反应（MCR）、使用L-脯氨酸作为环境友好型有机催化剂、氮杂维蒂希反应、使用β-环糊精（β-CD）作为超分子催化剂、超声辐射、微波辅助反应和紫外线（UV）辐射。据我们所知，这是第一篇专注于所有六种类型嘧啶并喹啉合成及其机理方面的综述。还提到了一些医学应用。
