One-pot Multicomponent Approach Research Articles

Synthesis of thiazolyl hydrazonothiazolamines and 1,3,4-thiadiazinyl hydrazonothiazolamines as a class of antimalarial agents.

Novel thiazolyl hydrazonothiazolamines and 1,3,4-thiadiazinyl hydrazonothiazolamines were synthesized by a facile one-pot multicomponent approach by the reaction of 2-amino-4-methyl-5-acetylthiazole, thiosemicarbazide or thiocarbohydrazide and phenacyl bromides or 3-(2-bromoacetyl)-2H-chromen-2-ones in acetic acid with good to excellent yields. These new compounds were screened in vitro for their antimalarial activity; among them, four compounds, 4h, 4i, 4k, 4l, showed moderate activity with half-maximal inhibitory concentration (IC50 ) values of 3.2, 2.7, 2.7, and 2.8 and 3.2, 3.2, 3.1, and 3.5 μM against chloroquine-sensitive and -resistant strains of Plasmodium falciparum, respectively. Compound 4l inhibited the ring stage growth of P. falciparum 3D7 at an IC90 concentration of 12.5 µM in a stage-specific assay method, where the culture is incubated with specific stages of P. falciparum for 12 hr, and no activity was found against the trophozoite and schizont stages, confirming that 4l may have potent action against the ring stage of P. falciparum.

Design, synthesis, molecular modelling, ADME prediction and anti-hyperglycemic evaluation of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors

The aim of the present study is to design and synthesis of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors. The target compounds 4a-n were synthesized by one-pot multicomponent approach with good yields and were characterized by various spectroscopic techniques and finally by single crystal X-ray diffraction method (4j). All the newly-synthesized derivatives have been screened for their α-glucosidase enzyme inhibition activity and acarbose taken as a standard drug. Among all the tested compounds, 4h has displayed excellent α-glucosidase enzyme inhibition activity with IC50 value 12.45 μM to the standard drug acarbose (IC50: 12.68 μM). Similarly, the compounds 4f and 4l have exhibited potent activity with IC50 values 14.47 μM and 17.27 μM respectively. Structure-activity relationship (SAR) studies of all the title compounds were established. The mode of binding interactions between the α-glucosidase enzyme and the compounds were studied. The drug-likeness properties (Lipinski parameters and in silico ADME properties) have predicted for the target compounds. The α-glucosidase inhibition, molecular docking and drug-likeness properties of the compounds 4h, 4f and 4l were suggested that these are promising hits for anti-diabetic activity.

One-pot synthesis of novel N,N-bis(isoxazol-5-yl)methyl tertiary arylamines via sequential diprop-3-ynylation and 1,3-dipolar cycloaddition from primary amines

A simple and efficient one-pot multicomponent approach for the synthesis of tertiary arylamines bearing N,N-bis(isoxazol-5-yl)methyl groups is developed through reactions including sequential diprop-3-ynylation of primary amines with propargyl bromide in the presence of calcium hydride in N,N-dimethylformamide, and 1,3-dipolar cycloaddition with nitrile oxides generated in situ from hydroximyl chlorides in DMF-Et3N. This protocol provides advantages such as high regioselectivity, easy operation, and moderate-to-good product yields with a wide substrate scope under mild conditions.

Design, synthesis, cytotoxicity, and molecular modeling study of 2,4,6-trisubstituted pyrimidines with anthranilate ester moiety

A series of 2,4,6-trisubstituted pyrimidines with antharanilic acid ester moiety have been designed and synthesized by employing a one-pot multicomponent approach from methyl 5-(ethynyl)anthranilate, aroyl or cinnamoyl chlorides and various amidines. All the compounds were evaluated for their cytotoxic activity with respect to model cancer cell lines (CEM-13, U-937, MDA-MB-231, BT-474, DU-145) using conventional MTT assays. Structure-activity relationship analysis revealed that 4,6-diarylpyrimidines 13–17, substituted with a pyridine or a pyrimidine ring in the 2 position displayed an increasing of activity compared to 2-methyl or 2-phenyl substituted pyrimidines. The 2-amino substututed compound 9 showed selectivity on the human monocyte-like cells U-937. Trisubstituted pyrimidines 18–21, containing a (E)-styryl substituent in the 6 position of the pyrimidine core, demonstrated an increasing of activity against the breast cancer cell lines MDA-MB-231, BT-474, and also against the human prostate cell lines DU-145. Compounds 18 and 20 shown the best potency towards the cancer cell lines MDA-MB-231; theirs activity was comparable with the activity of Doxorubicin on this cell lines. These compounds were confirmed to be cyclin-dependent kinase 9 (CDK9) inhibitors through in silico molecular modeling studies for the mode of action. The newly synthesized compounds may serve as lead molecules for the future research regarding the identification of new anticancer agents in the pyrimidine series.

One-pot Multicomponent Approach Towards the Synthesis of Heterocyclic Compounds by using β-cyclodextrin as a Catalyst

One-pot Multicomponent Approach Towards the Synthesis of Heterocyclic Compounds by using β-cyclodextrin as a Catalyst

One-Pot Assembly of Unsymmetrical Biaryl Thioglycosides through Chemoselective Palladium-Catalyzed Three-Component Tandem Reaction.

A range of unsymmetrical biaryls bearing thiosugars could be synthesized in a one-pot multicomponent approach using one catalytic palladium system that permitted the C-S and C-C bonds to be formed sequentially. The reaction showed a high selectivity and was applied to a broad variety of substrates giving access to novel glycosylated biaryl structures in good yields.

New prospects for the development of selective inhibitors of α -glucosidase based on coumarin-iminothiazolidinone hybrids: Synthesis, in-vitro biological screening and molecular docking analysis

Abstract α-Glucosidase inhibitors have extensively been exploited for the effective management of type 2 diabetes and associated complications by significantly reducing the postprandial increase in glucose and plasma insulin levels. In this endeavour, we designed and synthesized a new series of coumarinyl iminothiazolidinone hybrid compounds (6a‒o) using a one-pot multi-component approach. The hybrid structures were accessed in good chemical yields. The synthesized compounds were tested for their glucosidase inhibitory efficacy using acarbose as a standard inhibitor (IC50 = 38.2 ± 0.12 µM). In-vitro analysis of the hybrid molecules identified several potential leads for the development of potent glucosidase inhibitors with IC50 values in the range of 0.09‒0.92 µM with compound 6g being the most potent drug candidate (IC50 = 0.09 ± 0.001 µM). Furthermore, compound 6f was identified as the lead inhibitor against maltase-glucoamylase with comparable inhibitory efficacy to acarbose with an IC50 value of 0.07 ± 0.016 µM. Binding interactions of potent compounds with the key residues in the active site of the glucosidase enzyme were revealed by molecular docking analysis. In summary, these new structural leads based on the hybrid pharmacophores could be developed as potential inhibitors of α-glucosidase for treating postprandial hyperglycemia.

Novel Cu(I)-catalyzed one-pot multicomponent synthesis of the antiepileptic drug rufinamide

This work represents a new synthesis of the antiepileptic drug rufinamide, through a one-pot multicomponent approach employing a Cu(I) as a catalyst. In this methodology, 2,6-difluoro benzyl bromide reacts with NaN3 and propiolamide in the presence of 0.5 mol% [Cu(phen)(PPh3)2]NO3 as a catalyst under click condition to afford regioselectively rufinamide in 95% yield. The new protocol offers several advantages such as high yields, clean reaction profile, short reaction time, use of less toxic catalyst, environmentally friendly and one pot approach.

One-pot synthesis of bis (phenylimino dihydro thiazolyl-2H-chromene) derivatives

ABSTRACTA novel series of bis (phenylimino dihydro thiazolyl-2H-chromene) derivatives have been synthesized through an efficient one-pot multicomponent approach involving different substituted of 3-(2-bromoacetyl)-2H-chromen-2-ones, phenyl isothiocyanates and para-phenylenediamine in presence of dimethylformamide solvent. The target compounds were obtained in a shorter reaction time through simple reaction work up with good yields. All the synthesized products were characterized by their spectral and analytical data like IR, 1H NMR, 13C NMR, Roesy, and mass spectral data.

A one-pot multicomponent approach to a new series of morphine derivatives and their biological evaluation.

A novel and facile domino reaction has been developed to synthesize a variety of new derivatives from hydromorphone, amines and paraformaldehyde in good yields in a catalyst-free fashion with high atom efficiency. The products show a mixed MOR/DOR biological characteristic which makes them valuable for further study as opioid analgesics.

Synthesis of novel 2-aryl-3-benzoyl-1H-benzo[f]indole-4,9-diones using a domino reaction

A convenient one-pot multicomponent synthetic approach was developed for the synthesis of novel 2-aryl-3-benzoyl-1H-benzo[f]indole-4,9-diones using 2-amino-1,4-naphthoquinone, N-acylmethylpyridinium bromides, and a variety of aromatic aldehydes.

ChemInform Abstract: One‐Pot Access to a Privileged Library of Six Membered Nitrogenous Heterocycles Through Multi‐Component Cascade Approach

AbstractReview: 174 refs.

ChemInform Abstract: Site Selective Synthesis of Cytotoxic 1,3,6‐Trisubstituted 3,6‐Diunsaturated (3Z,6Z)‐2,5‐Diketopiperazines via a One‐Pot Multicomponent Method.

AbstractA one‐pot protocol is presented for the reaction of 1,4‐diacetyl‐2,5‐diketopiperazine with a halohydrocarbon and one or two different aldehydes.

Site selective synthesis of cytotoxic 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazines via a one-pot multicomponent method

A one-pot multicomponent approach was established for site selective synthesis of novel 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazine derivatives with high stereoselectivity. The computational studies revealed that the steric hindrances between the 2-hydrogen atoms on the aromatic rings and the carbonyl, as well as the steric repulsions between the hydrogen atoms of the CH group in the benzylidene and the CH2 group in the N-alkylative part might be responsible for the Z/E selectivity. Compound (3Z,6Z)-3h (IC50=11 nM) has a close activity to the positive compound plinabulin (IC50=15 nM) against the cancer cell line HL60.

One-pot access to a privileged library of six membered nitrogenous heterocycles through multi-component cascade approach

The presence of heterocycles and heteroaromatics as ubiquitous components in a diverse variety of synthetic drugs, biologically active molecules, and natural products has inspired the researchers to develop new strategies and technologies for their easy accessibility. Among them, six membered nitrogenous heterocycles gained immense interest, and significant efforts have been made to the development of synthetic strategies which could lead to the discovery of architecturally complex and diverse molecules with high efficiency, low cost, less organic waste and shorter reaction time. Access to such systems by one-pot multi-component approach with inherent advantages of step-economy, operational simplicity, synthetic efficiency, and environmental compatibility is particularly attractive. The current review article highlights the recent developments in the synthesis of six membered nitrogen-containing heterocyclic scaffolds through one-pot multi-component assembly approach.

Synthesis, biological activity evaluation and molecular docking studies of novel coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes.

A novel series of coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes (4a-o) were synthesized via an efficient, one-pot multicomponent approach involving 3-(2-bromoacetyl)coumarins (1a-g), thiosemicarbazide (2) and substituted acetophenones (3a-c) utilizing Vilsmeier-Haack reaction condition with good yields. The title compounds structure was elucidated by spectroscopic data (IR, NMR and Mass) and elemental analysis. All the synthesized compounds were screened for their in vitro cytotoxic activity against MCF-7, DU-145 and HeLa cell lines and studied detailed about molecular interaction of probable target protein human microsomal cytochrome CYP450 2A6 using docking simulation. These coumarin derivatives were exhibiting moderate to appreciable cytotoxic activities. The compounds 4m and 4n exhibited significant cytotoxic activity with IC50 values having 5.75 and 6.25μM against HeLa cell line. Similarly compound 4n also exhibiting good anti cancer property and antibacterial activity against DU-145 cell line and Gram negative bacterial strains.

Synthesis and cytotoxic evaluation of novel dihydrobenzo[h]cinnoline-5,6-diones

A convenient one-pot multicomponent synthetic approach was developed en route to novel functionalized dihydrobenzo[h]cinnoline-5,6-diones using 2-hydroxy-1,4-naphthoquinone, methylhydrazine, and a variety of aromatic aldehydes. Fifteen new derivatives were thus prepared and subsequently evaluated in terms of their cytotoxicity profile, revealing a promising anticancer activity of nine of the compounds against KB and Hep-G2 human tumor cell lines.

Solvent-free one-pot synthesis of polysubstituted tetrahydropyrimidines and their antioxidant and antimicrobial properties

A versatile and highly efficient one-pot multicomponent approach for the synthesis of novel multisubstituted tetrahydropyrimidine (dimethyl/diethyl-1,3-disubstituted-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate) derivatives catalyzed by Bromo(dimethylsulfonium) bromide under solvent-free conditions has been developed. The protocol is eco-friendly, operationally simple, and proceeds in short reaction time, providing high-yield, high-purity (90–95 %) stable target compounds without any side products. Further, the scope of this protocol extended to aliphatic substrates, thus establishing the versatility of the catalyst. The lead compounds were screened for antioxidant and antimicrobial activities. Among them, compounds 4a, 4d, 4e, 4j exhibited excellent antibacterial activity when compared with the standard gentamycin. Compounds 4e and 4k exhibited excellent antifungal activity in comparison with the standard itraconazole. The results of this study revealed that all synthesized compounds were significantly scavenged DPPH free radicals in a concentration-dependent manner. The IC50 values of the compounds is between 13.28 and 23.16 µM when compared with the standard ascorbic acid. Compound 4f was found to be a good antioxidant. The synthesis of polysubstituted tetrahydropyrimidines (dimethyl/diethyl-1,3-disubstituted-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate) derivatives from but-2-ynedioates, amines, and formaldehyde via a one-pot multicomponent reaction is reported. The reactions were performed under solvent-free and mild conditions with shorter reaction times, high purity, and high yield. The obtained products are interesting heterocyclic compounds containing ester functional groups and exhibited excellent antibacterial activity and moderate-to-good antioxidant properties.

ChemInform Abstract: Isocyanide‐Based One‐Pot Three‐Component Synthesis of Novel Spiroiminolactone Derivatives in Water.

A new and efficient isocyanide-based one-pot multi-component approach for the synthesis of novel spiroiminolactone derivatives is described. Products were obtained by a three-component condensation reaction of 1,3-diones, reactive cyclic carbonyl compounds, and isocyanides in the presence of a catalytic amount of tetrabutylammonium hydrogensulfate in water. Using this method, target compounds were synthesized with great efficiency and atom economy.

L-Proline catalyzed one-pot multi-component synthesis of 2-(1,3-diphenyl-1H-pyrazol-4-yl)quinazolin-4(3H)-one derivatives and their biological studies

Abstract A new series of quinazolin-4(3 H )-one derivatives containing a (1,3-diphenyl-1 H -pyrazol-4-yl) core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized using an l -proline catalyzed one-pot multi-component reaction approach. All the synthesized compounds were characterized and screened for their antimicrobial, antifungal and anti-tubercular activities.