Abstract
A multicomponent domino reaction of enaminone, malononitrile, and o-phthalaldehyde has been established, providing direct access to novel highly functionalized pentacyclic cyclopenta [b] indeno [1, 2, 3-de] [1,8] naphthyridine derivatives. The simplicity of execution, readily available substrates, high yields, excellent functional group tolerance, scalability, and good scores of environmental parameters make this synthetic strategy more sustainable and worthy of further attention. This one-pot transformation, which involved multiple steps and did not require the use of a catalyst, constructed four new C-C bonds, two new C-N bonds, and three new rings, with efficient use of all reactants. Furthermore, we performed in silico molecular docking analysis for prediction of anticancer (against human topoisomerase IIβ protein) and antimicrobial (against E.coli. DNA gyrase B protein) activities. Drug likeness and ADMET studies were also predicted. Overall investigation indicates that compound 6i may serve as a candidate that could be developed as potential anticancer and antimicrobial agent among all.
Highlights
A series of novel 1,8-naphthyridine derivatives are synthesized via a four-component domino reaction with no more than 20 minutes of microwave irradiation
It is noteworthy that we synthesized the starting material enaminone (3a-i) under microwave irradiation, starting with cyclopentane-1, 3-dione (1), and various amines (2a-i) in neat at 160°C for 10 min. e reaction and products are summarized in Scheme 2. is work represents the first example of synthesizing different enaminones through this simple and green methodology
A diverse collection of 1,8-naphthyridine derivatives were rapidly constructed with excellent yields in short reaction times by heating a mixture of different enaminones, malononitrile, and o-phthalaldehyde in DMF, without a catalyst, under microwave irradiation
Summary
Among the six possible (1,5−, 1,6−, 1,7−, 1,8−, 2,6−, and 2,7−) isomeric pyridopyridines, [9, 10] 1,8-naphthyridines and their derivatives have diverse potential in clinical and medicinal chemistry due to their anti-inflammatory, [11] antimalarial, [12] antihypertensive, [13] gastric antisecretory, [14] antiplatelet aggregation, [15] AChE inhibitory, [16] antihistaminic, [2] antimicrobial [17, 18], and anticancer [19,20,21] activities (Figure 1). In continuation to our ongoing endeavors to prepare novel biologically active nitrogen containing heterocyclic entities, by using green and benign MCR protocols, [38, 39] we report a domino four-component strategy for the efficient synthesis of highly functionalized pentacyclic cyclopenta [b] indeno [1, 2, 3-de] [1,8] naphthyridine derivatives by utilizing cheap and commercially available reagents, that is, different enaminones, malononitrile, and o-phthalaldehyde under appropriate catalyst-free and mild microwave conditions (Scheme 1).
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