Browsing by Author "Kulkarni, Manohar V."

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5-phenylpyridazinones - A serendipitous route from coumarins
(2008-07-07)
Ghate, Manjunath D.
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Jadhav, Vithal B.
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Shastri, Lokesh A.
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Kulkarni, Manohar V.
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Kulkarni, Geetha M.
A new route of the ring transformation has been discovered during the reaction of 4-bromomethylcoumarins with hydrazine hydrate leading to the formation of pharmacologically important pyridazinones in a single step with very high yields. These so obtained pyridazinones have the potential for further functional group interconversions. (C) 2008 Elsevier Ltd. All rights reserved.
Ionic liquid supported synthesis of tricyclic pyrimido [1,2-a]benzimidazoles by a telescoped Michael/hetero annulation strategy
(2013)
Selvaraju, Manikandan
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Shiu, Wei-Shuen
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Kulkarni, Manohar V.
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Sun, Chung-Ming
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應用化學系
A telescoped sequence involves the reaction of cationic imidazolium attached 2-aminobenzimidazoles with in situ generated 1,1-dicyano-2-aryl ethylenes was explored for the regioselective synthesis of pyrimido[1,2-a]benzimidazoles. The perceived regioselectivity was presumed in terms of preferential Michael addition of 2-aminobenzimidazole followed by intramolecular annulation to the exclusive formation of 4-iminopyrimidines on an ionic liquid support. A plausible mechanistic pathway for their selective formation is discussed and fully supported by X-ray analysis. The present strategy reveals both the amine function and the ring nitrogen in substituted 2-aminobenzimidazoles are active sites for nucleophilic attack on alpha,beta-unsaturated nitriles.
Parallel synthesis of 2-sulphanylated bis-benzimidazoles on soluble polymer support
(2008-05-01)
Chang, Chia-Mao
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Kulkarni, Manohar V.
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Chen, Chih-Hau
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Wang, Chi-Hsiang
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Sun, Chung-Ming
A well-sustained multistep synthetic protocol has been designed for the PEG-functionalized aromatic acid amide to generate a molecular library of 2-alkylthio bis-benzimidazoles. An attempted synthesis of benzimidazole-2-thiol in dichloromethane has led to S-chloromethyl methyl sulfides, mimicking bacterial enzymatic systems. Regioselective S-alkylation was brought about under controlled conditions using a mild base at room temperature. The polymer-free compounds, 2-sulfanylated bisbenzimidazoles, were obtained in high yields and high purities. Chemical shift changes in proton and carbon NMR-have been employed to monitor the progress of the reaction steps and to prove the site of S-alkylation, respectively.
Recent advances in coumarins and 1-azacoumarins as versatile biodynamic agents
(2006)
Kulkarni, Manohar V.
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Kulkarni, Geeta M.
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Lin, Chao-Hsiung
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Sun, Chung-Ming
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應用化學系
Coumarins, also referred as benzopyran-2-ones, and their corresponding nitrogen counterpart, 1-azacoumarins also referred to as carbostyrils, are a family of nature-occurring factories and lactams respectively. The plant extracts containing coumarin-related heterocycles, which were employed as herbal remedies in early days, have now been extensively studied for their biological activities. These investigations have revealed their potentials as versatile biodynamic agents. For example, coumarins with phenolic hydroxyl groups have the ability to scavenge reactive oxygen species and thus prevent the formation of 5-HETE and HHT in the arachidonic pathway of inflammation suppression. Recent in vivo studies have revealed the role of coumarins in hepatotoxicity and also ill depletion of cytochrome P450. Similarly 1-azacoumarins which is part of quinoline alkaloids, are known for their diverse biological activity and recently, a 6-functionalized 1-aza coumarins are undergoing human clinical trials as an orally active anti-tumor drug in view of its farnesyl protein-inhibiting activity in the nanomolar range. Furthermore, several synthetic coumarins with a variety of pharmacophoric groups at C-3, C-4 and C-7 positions have been intensively screened for anti-microbial, anti-HIV, anti-cancer, lipid-lowering, anti-oxidant, and anti-coagulation activities. Specifically, coumarin-3-sulfonamides and carboxamides were reported to exhibit selective cytotoxicity against mammalian cancer cell lines. The C4-substituted aryloxymethyl, arylaminomethyl, and dichloroacetamidomethyl coumarins, along with the corresponding 1-azacoumarins, have been demonstrated to be potential anti-microbial and anti-inflammatory agents. To expand the structural diversity of synthetic courmarins for biological functions, attempts have also been made to attach a chloramphenicol side chain at C-3 position of courmarin. In addition, the bi- and tri-heterocyclic coumarins and 1-azacoumarins with benzofuran, furan and thiazole ring systems along with biocompatible fragments like vanillin have shown remarkable potency as anti-inflammatory agents ill animal models. Photobiological studies oil pyridine-fused polycyclic coumarins have highlighted their potential as thymine dimer photosensitisers and the structurally related compounds of both coumarin and carbostyrils have also been found to act via the DNA gyrase pathway in their anti-bacterial activity. Apart from the above works, the present review also addresses the potential roles of coumarins and carbostyrils as protease inhibitors, or fluorescent probes in mechanistic investigation of biochemical pathways, and their application for QSAR in theoretical studies. Though 1-Azacoumarins have received less attention as compared to coumarins in the literature, an attempt has been made to compare both the systems at various stages, so that it can spark new thoughts on synthetic methodologies, reactivity pattern and biological activities.
Regioselective one-pot three component synthesis of chiral 2-iminoselenazolines under sonication
(2015-01-01)
Chang, Wong-Jin
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Kulkarni, Manohar V.
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Sun, Chung-Ming
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應用化學系
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Department of Applied Chemistry
A one-pot multi component reaction of selenoureas, which are in situ generated from L-amino esters and isoselenocyanates, with alpha-bromoketone under ultrasonication. Selenourea and alpha-bromoketones formed 2-iminoselenazoles through a Hantzsch selenazole-type reaction. The steric effect of the alpha-substituted bromoketones on the rate of the tandem reaction was studied to understand the reaction mechanism by isolating the key reaction intermediate, 2-iminoselenol.
Rhodium-Catalyzed Regioselective Synthesis of Isocoumarins through Benzothiadiazine-Fused Frameworks
(2016-08-05)
Dalvi, Prashant B.
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Lin, Kuang-Ling
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Kulkarni, Manohar V.
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Sun, Chung-Ming
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應用化學系
An unprecedented two-step, one-pot synthesis of benzimidazothiadiazine 5,5-dioxides is presented. Reaction condition based regioselectivity has been achieved where fused benzimidazo[1,2-b][1,2,4]thiadiazines are exclusively formed under thermal conditions, whereas benzimidazo[2,1-c][1,2,4]thiadiazines were created only under microwave irradiation. The salient features of this protocol include a regioselective sulfonylation of 2-aminobenzimidazole with o-halo sulfonyl chlorides followed by N-C bond formation. The acid forms of these fused regioisomers have been used to introduce novel guanidine containing isocoumarin frameworks.
Synthesis of structurally diverse benzimidazolyl benzimidazolones by application of soluble polymer support
(2008-06-30)
Chen, Hsia-Yuan
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Kulkarni, Manohar V.
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Chen, Chih-Hau
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Sun, Chung-Ming
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應用化學系
Chemical stability and reactivity of a bifunctional polymer conjugate containing an ortho-amino arylamide linkage have been successfully exploited to achieve a parallel synthesis of methoxycarbonylated head-tail bis-benzimidazoles. Regioselective alkylation of the two nitrogens in the benzimidazolone moiety has been carried out by ipso-fluoro displacement, and N-alkylation to generate two diversities. Cleavage of the polymer support has resulted in two libraries of di- and tri-substituted benzimidazolyl benzimidazolones in high purity and high yield. All reaction steps have been monitored by (1)H NMR on the support directly. (c) 2008 Elsevier Ltd. All rights reserved.
Unusual Anisotropic Effects from 1,3-Dipolar Cycloadducts of 4-Azidomethyl Coumarins
(2010-01-01)
Kusanur, Raviraj A.
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Kulkarni, Manohar V.
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Kulkarni, Geetha M.
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Nayak, Susanta K.
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Row, Tayur N. Guru
4-Bromomethylcoumarins (1) reacted with sodium azide in aqueous acetone to give 4-azidomethyl-coumarins (2), which underwent 1,3-dipolar cycloaddition with acetylenic dipolarophiles to give triazoles (3). These triazoles (3) have been found to exhibit interesting variations in the chemical shifts of C(3)-H and C(4)-methylene protons. Protonation studies indicate that the shielding effect of the C(3)-H of coumarin is due to pi-electrons of the triazole ring, further supported by diffraction and computational studies.