Kalegowda Shivashankar

Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin.

A series of new and novel coumarin-6-sulfonamides with a free C4-azidomethyl group have been synthesized as antimicrobials in three steps starting from 7-methyl-4-bromomethylcoumarin 1. The reaction of 1 with chlorosulfonic acid was found to yield the corresponding 6-sulfonylchloride 2, which when treated with sodium azide led to intermediate 3. The title sulfonamides 5a-y were obtained from the reaction of 3 with various aromatic amines 4 in refluxing benzene. The chemical structures of the compounds were elucidated by IR, NMR and LC-MS spectral data. All the synthesized compounds have been screened for their in vitro anti-bacterial and anti-fungal activities. Some of the compounds have been found to be active against both bacterial species at a concentration of 1 microg/mL.

Microwave assisted synthesis of dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones; synthesis, in vitro antimicrobial and anticancer activities of novel coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones.

The present article describes the synthesis of dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one (2a-h) under microwave irradiation. The product was obtained in excellent yield (74-94%) in a shorter reaction time (2 min). These molecules (2a, b) further reacted with various substituted 4-bromomethylcoumarins (3a-f) to yield a new series of coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones (4a-h). The structure of all the synthesized compounds were confirmed by spectral studies and screened for their in vitro antibacterial activity against three Gram-positive bacteria viz., Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and three Gram-negative bacteria viz., Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Fusarium oxysporum, Penicillium chrysogenum and anticancer activity against Daltons Ascitic Lymphoma (DAL) cell line. In general, all the compounds possessed better antifungal properties than antibacterial properties. The coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one (4g) (R = i-Pr, R₁ = 6-Cl) was found to be the most potent cytotoxic compound (88%) against Daltons Ascitic Lymphoma cell line at the concentration of 100 μg/mL.

Iodine-catalyzed three component reaction: a novel synthesis of 2-aryl-imidazo[1,2-a]pyridine scaffolds

A facile and efficient protocol for the synthesis of novel 2-aryl-imidazo[1,2-a]pyridines has been developed via a one-pot reaction of aromatic aldehydes with 2-amino-5-chloropyridine and tert-butylisocyanide in the presence of I2 in ethanol at 70 °C. The present approach offers the advantages of a clean and simple methodology, high atom-economy, mild conditions, short reaction times, wide substrate scope, low environmental impact and high yield.

Multicomponent reaction of benzyl halides: Synthesis of [1,2,4]triazolo/benzimidazolo quinazolinones

ABSTRACT We demonstrated a simple, highly efficient, one-pot method to construct triazolo/benzimidazolo quinazolinones through a cascade of oxidation, Knoevenagel condensation, and Michael addition followed by cyclization and dehydration. This protocol tolerates easily available benzyl halides, 2-amino benzimidazole/3-amino-1,2,4-triazole, and α-hydroxy C-H acids as starting materials using trimethyl amine N-oxide in ethanol. To the best of our knowledge, this is the first example of synthesis of triazolo/benzimidazolo quinazolinones directly from benzyl halides in one pot. Simple procedure, environmental friendliness, mild reaction conditions, and good yields are the attractive features of this method. GRAPHICAL ABSTRACT

Synthesis of N1 and N2 coumarin substituted 1,2,3-triazole isomers via click chemistry approach

ABSTRACT The synthesis of N1 and N2 coumarin substituted 1,2,3-triazole isomers from terminal alkynes, sodium azide, and 4-bromomethylcoumarins in the presence of triethylamine as a base and CuI as a catalyst in good yield are reported. The molecular structure of compounds 3g and 5d are established by single-crystal analysis. GRAPHICAL ABSTRACT

One pot synthesis of pyran-based heterocycles from benzyl halides as key reagents

Pyridine N-oxide and silver oxide have been demonstrated to be efficient and mild reagents for the one pot synthesis of pyran analogues from a variety of benzyl halides. Benzyl halides are oxidized in situ to aldehydes, which in turn undergo a three-component reaction with malanonitrile/ethylcyanoacetate and α-hydroxy C–H acids to yield pyran analogues. The attractive features of this process are mild reaction conditions, short reaction times, broad functional group tolerance, easy isolation of products and excellent yields. Thus, the current method utilizes benzyl halides as key reagents instead of benzaldehydes.

One pot synthesis of acridine analogues from 1,2-diols as key reagents

Lead tetraacetate have been demonstrated to be efficient, low cost and mild reagents for the one pot synthesis of acridine derivatives from a variety of 1,2-diols. 1,2-Diols are oxidised in situ to aldehydes, which in turn undergo reaction with dimedone and ammonium acetate to yield acridine derivatives. The attractive features of this process are mild reaction conditions, short reaction times, broad functional group tolerance, easy isolation of products and excellent yields. Thus, the current method utilises 1,2-diols instead of benzaldehydes to synthesise acridines derivatives.

Synthesis of pyridazinones via molecular-iodine-mediated cleavage of 4-bromomethylcoumarin precursors

ABSTRACT A facile and an efficient protocol for the synthesis of pyridazinones via molecular-iodine-mediated cleavage of 4-bromomethylcoumarin precursors in the presence of I2 in ethanol at 70 °C is reported. The present approach replaced the basic condition (K2CO3) with Lewis acidic condition. GRAPHICAL ABSTRACT

Molecular docking studies of benzimidazopyrimidine and coumarin substituted benzimidazopyrimidine derivatives: As potential human Aurora A kinase inhibitors

Protein kinases are important drug targets in human cancers, inflammation and metabolic diseases. Docking studies was performed for all the benzimidazopyrimidine and coumarin substituted benzimidazopyridimine derivatives with human Aurora A kinase target (3FDN) employing flexible ligand docking approach by using AutoDock 4.2. All the compounds were found to have minimum binding energy ranging from -6.26 to -9.29 kJ/mol. Among the molecules tested for docking study, 10-(6-Bromo-2-oxo- 2H-chromen-4-ylmethyl)-2-isopropyl-10H-benzo[4,5]imidazo[1,2-a]pyrimidin-4-one (2k) showed minimum binding energy (-9.29 kJ/mol) with ligand efficiency of -0.31. All the ligands were docked deeply within the binding pocket region of 3FDN showing hydrogen bonds with Ala 213 and Asn 261. The docking study results showed that these derivatives are excellent inhibitor of human Aurora A kinase target; and also all these docked compounds have good inhibition constant, vdW + Hbond + desolv energy with best RMSD value.

Four component synthesis of highly functionalized pyrano[2,3-c]pyrazoles from benzyl halides

ABSTRACT N-methylmorpholine N-oxide and silver oxide (Ag2O) oxidized four component reaction for the preparation of pyranopyrazole with different substituted pattern have been developed which provides rapid access to a library of compounds in good to excellent yields by using benzyl halide, malanonitrile/ethyl cyanoacetate, diethylacetylenedicarboxylate/ethyl acetoacetate and hydrazine hydrate as reactants. This transformation involves the breaking of one C‒O bond and formation of 2 C–C, 2 C–N, and a C‒O bond leading to the formation of a five and six membered ring in one pot operation. GRAPHICAL ABSTRACT