A series of pyrano[4,3-b][1]benzopyranones (7a–t) were synthesized through hetero-Diels-Alder reaction of substituted 3-formylchromones (5) with enol ethers (6), characterized by IR, 1H NMR, 13C NMR, and mass spectral techniques. All the compounds were evaluated for antimicrobial activity against various bacterial and fungal strains, found to possess significant inhibitory potential, particularly, compounds bearing electron withdrawing group -fluoro such as 7i and 7h. Compounds were also tested and displayed a significant inhibitory potential against methicillin-resistant Staphylococcus aureus (MRSA). 1. Introduction Despite decades of extensive progress in treatment and prevention, infectious diseases remain a major cause of death and are responsible for worsening the living conditions of many millions of people around the world [1]. Additionally, resistance to known antibiotics is also a serious problem and presents a challenge for the medicinal chemists to develop new effective molecular entities against pathogenic microorganism resistant to available current treatments [2]. Chromones are an important class of heterocyclic molecules naturally occurring, and synthetic analogs are found to display a wide range of pharmacological activities such as antimicrobial, anticancer, neuroprotective, HIV-inhibitory, antifungal activities, and antioxidant [3–9]. Natural products such as aposhaerin A (1), isolated from Aposhaeria sp. possess remarkable antibacterial activity [10]. Recently, we have reported that 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl-) chromen-4-ones (2) possess significant antibacterial activity against Shigella flexneri (Figure 1) [11]. Figure 1: Chromone based compounds as antimicrobial agents. Similarly, pyran moiety is widely present in animal and plant kingdom; it exhibits diverse pharmacological activities such as antimicrobial, antiviral, antiproliferative, antitumor, antiinflammatory [12–16]. Pyrano[3,2-c]chromene derivatives (3a–c), bearing a 2-thiophenoxyquinoline nucleus, have been found to display excellent antibacterial activity against B. subtilis, E. coli, and P. aeruginosa, respectively, [17]. 2-Amino-3-cyano-6-(3,5-dibromo-4-methoxyphenyl)-4-arylpyrans (4) have been found to exhibit potent antimicrobial and antimycobacterial activity (Figure 2) [18]. Figure 2: Pyran based compounds as antimicrobial agents. Taking cognizance of high antimicrobial activity of both chromone and pyran derivatives, it was decided to synthesize chromone fused pyrans and evaluate against various pathogenic bacterial and fungal strains. 2. Results and
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