Raju Ranjith Kumar

Antimycobacterial activity of novel 1,2,4-oxadiazole-pyranopyridine/chromene hybrids generated by chemoselective 1,3-dipolar cycloadditions of nitrile oxides.

The 1,3-dipolar cycloaddition of nitrile oxides generated in situ from benzohydroximinoyl chloride and triethylamine to 2-aminopyranopyridine-3-carbonitriles and 2-aminochromene-3-carbonitriles occurred chemoselectively furnishing novel 1,2,4-oxadiazole-pyranopyridine/chromene hybrid heterocycles in moderate yields. In vitro screening of these compounds against Mycobacterium tuberculosis H37Rv (MTB) disclosed that the 1,2,4-oxadiazole-pyranopyridine hybrids display enhanced activity relative to the 1,2,4-oxadiazole-chromene hybrids. Among the compounds screened, 3-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]-4-(2,4-dichlorophenyl)-8-[(E)-(2,4-dichlorophenyl)-methylidene]-6-methyl-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridin-2-amine (MIC: 0.31 μM) is 1.2, 15.2 and 24.6 times more active than standard antitubercular drugs, viz. isoniazid, ciprofloxacin and ethambutol, respectively.

Four-component domino strategy for the combinatorial synthesis of novel 1,4-dihydropyrano[2,3-c]pyrazol-6-amines.

An efficient one-pot four-component domino protocol for the combinatorial synthesis of novel 1,4-dihydropyrano[2,3-c]pyrazol-6-amines has been achieved. This transformation presumably occurs via cyclization-Knoevenagel condensation-Michael addition-tautomerism-intramolecular O-cyclization-elimination sequence of reactions. The significant features of this reaction include expedient one-pot process, short reaction time, no column chromatographic purification, excellent yield, and readily available starting materials.

Ultrasound-assisted sequential multicomponent strategy for the combinatorial synthesis of novel coumarin hybrids.

The present investigation reports an easy access to a library of novel spiro-oxindole-pyrrolizine or pyrrolo[1,2-c]thiazole fused coumarin hybrid heterocycles through a one-pot sequential four-component reactions of 2,2-dimethyl-1,3-dioxane-4,6-dione, salicylaldehydes, isatins, and cyclic α-amino acids under ultrasound irradiation.

2-Oxo Driven Unconventional reactions: Microwave Assisted Approaches to Tetrahydrofuro[3,2-d]oxazoles and Furanones.

A highly efficient, novel, microwave-assisted, metal-free, diastereoselective synthesis of tetrahydrofuro[3,2-d]oxazole is disclosed. The synthesis of napthoxazoles is achieved for the first time without the aid of an external catalyst. On the contrary, our reactions generated naphthofuranones when treated in the presence of metals in microwave/thermal conditions. The unusual behavior of our reactions has further been explored in the generation of furanones from tetrahydrofuro[3,2-d]oxazole through the use of metals.

A Novel One-Pot Green Synthesis of Dispirooxindolo-pyrrolidines via 1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides

A facile synthesis of dispirooxindolopyrrolidines has been accomplished via a one-pot three component 1,3-dipolar cycloaddition reaction. The reaction of azomethine ylides generated in situ from L-phenylalanine and substituted isatins with a series of unusual (E)-2-oxoindolino-3-ylidene acetophenone dipolarophiles in the ionic liquid 1-butyl-3-methylimidazolium bromide [bmim]BF4, furnished the cycloadducts in good yields, with the regioisomers 5a–f being obtained with high selectivity. Furthermore, the recyclability of [bmim]BF4, up to five times, was also investigated.

Ionic Liquid-Promoted Synthesis and Cholinesterase Inhibitory Activity of Highly Functionalized Spiropyrrolidines

A library of novel, highly functionalized spiropyrrolidines has been synthesized stereoselectively for the first time in ionic liquid medium employing [3+2] cycloaddition of a series of 2-arylmethylidene-5,6-dimethoxy-2,3-dihydro-1H-inden-1-ones with an unexplored azomethine ylide derived from acenaphthenequinone or isatin and tryptophan. These compounds were evaluated in vitro for their acetylcholinesterase and butyrylcholinesterase inhibitory activities. Molecular modelling simulation was performed to determine the binding interaction and orientation of these molecules in the active site gorge of the respective receptors.

Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles

The stereoselective syntheses of a library of novel spiro-tethered pyrazolo[3,4-b]quinoline-pyrrolidine/pyrrolothiazole/indolizine-oxindole/acenaphthene hybrid heterocycles have been achieved through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ from α-amino acids and 1,2-diketones to dipolarophiles derived from pyrazolo[3,4-b]quinoline derivatives.

A one-pot domino synthesis and discovery of highly functionalized dihydrobenzo[b]thiophenes as AChE inhibitors

A library of novel 5-amino-2,7-diaryl-2,3-dihydrobenzo[b]thiophene-4,6-dicarbonitriles have been synthesized regioselectively in good yields through the one-pot domino reactions of 5-aryldihydro-3(2H)-thiophenones, malononitrile and aromatic aldehydes in the presence of morpholine. This transformation presumably involves Knoevenagel condensation-Michael addition-intramolecular Thorpe-Ziegler cyclization-Tautomerization-Elimination sequence of reactions. These compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity and 5-amino-2,7-bis(4-methoxyphenyl)-2,3-dihydrobenzo[b]thiophene-4,6-dicarbonitrile was found to be the most potent against AChE with IC50 4.16 μmol/L.

Sequential 1,3-Dipolar Cycloadditions in the Synthesis of Novel Tri-spiro Cyclohexanones and Piperidin-4-ones

Abstract The sequential 1,3-dipolar cycloadditions of azomethine ylide and nitrile oxide to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones and 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel tri-spiro heterocycles comprising isoxazoline, pyrrolidine and acenaphthylen-1(2H)-one rings in good yields and stereoselectivity.

Divergent Reactivity of Amino Acid Alkyl Ester Hydrochlorides with 2-Oxoaldehydes: Role of Selenium Dioxide To Promote Regioselective Synthesis of Imidazoles

Novel amino acid substituted imidazoles engendered from amino acid alkyl ester hydrochlorides and 2-oxoaldehydes as a result of selenium dioxide promoted unconventional reaction in a basic environment is presented for the first time. Despite the nature of the 2-oxoaldehydes/amino acids used, the imidazoles generated had a functional core structure, and all of the reactions meticulously retained regioselectivity. The imperative feature of these reactions was the uniqueness of selenium dioxide in fixing two nitrogen atoms from amino acids through an in situ generated ArCOCHN1N2 system.