Comprehensive methodologies for synthesizing tricyclic fused pyrimidoquinolines of biological relevance: a review

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 via 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 (UV₃₆₅) 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.