scholarly journals Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1963 ◽  
Author(s):  
Sarra Boudriga ◽  
Saoussen Haddad ◽  
Vikneswaran Murugaiyah ◽  
Moheddine Askri ◽  
Michael Knorr ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Cycloaddition Reaction ◽  
Docking Study ◽  
X Ray Diffraction ◽  
Molecular Docking Study ◽  
Reaction Conditions ◽  
One Pot ◽  
X Ray ◽  
Cholinesterase Inhibitory Activity ◽  
Ache Inhibitory Activity

A novel one-pot [3+2]-cycloaddition reaction of (E)-3-arylidene-1-phenyl-succinimides, cyclic 1,2-diketones (isatin, 5-chloro-isatin and acenaphtenequinone), and diverse α-aminoacids such as 2-phenylglycine or sarcosine is reported. The reaction provides succinimide-substituted dispiropyrrolidine derivatives with high regio- and diastereoselectivities under mild reaction conditions. The stereochemistry of these N-heterocycles has been confirmed by four X-ray diffraction studies. Several synthetized compounds show higher inhibition on acetylcholinesterase (AChE) than butyrylcholinesterase (BChE). Of the 17 synthesized compounds tested, five exhibit good AChE inhibition with IC50 of 11.42 to 22.21 µM. A molecular docking study has also been undertaken for compound 4n possessing the most potent AChE inhibitory activity, disclosing its binding to the peripheral anionic site of AChE enzymes.

Replacing sulfonate by carboxylate: application of pyridyliminocarboxylato copper(II) complexes in rac-lactide polymerization and Chan–Evans–Lam coupling

2019 ◽  
Vol 97 (3) ◽  
pp. 178-190 ◽  
Author(s):  
Valérie Hardouin Duparc ◽  
Clémentine Dimeck ◽  
Frank Schaper
Keyword(s):  
Molecular Sieves ◽  
Weight Control ◽  
Phenylboronic Acid ◽  
Side Reactions ◽  
X Ray Diffraction ◽  
Reaction Conditions ◽  
One Pot ◽  
X Ray ◽  
Induction Periods ◽  
Lactide Polymerization

Copper(II) complexes carrying pyridylmethyleneaminobenzoate or –propanoate ligands, LCuX, were prepared in one-pot reactions from pyridinecarboxaldehyde, aminobenzoic acid or β-alanine, and CuX2 (X = Cl, NO3, OAc, or OTf). All complexes were characterized by single-crystal X-ray diffraction studies and formed either dimers, tetramers, or coordination polymers. Attempted preparation of the respective alkoxide complexes, LCu(OR), was unsuccessful, but use of LCuX/NaOMe mixtures in rac-lactide polymerization indicated under some conditions coordination–insertion polymerization via a copper alkoxide as the mechanism. The complexes performed poorly in rac-lactide polymerization, showing low activities (12 h to completion at 140 °C), low to moderate heterotacticity (Pr = 0.6–0.8), and poor polymer molecular weight control (intramolecular transesterification). They were competent catalysts for Chan–Evans–Lam couplings with phenylboronic acid, without any indication of side reactions such as deboration or aryl homocoupling. The complexes were active in undried methanol, without addition of base, ligand, or molecular sieves. Aniline, n-octylamine, and cyclohexylamine were coupled quantitatively under identical reaction conditions. There is only little influence of the anion on activities (less than a factor of 2) but a strong influence on induction periods. The complexes were not active in CEL coupling with alcohols, phenols, or alkylboronic acids.

Regio- and Diastereoselective Synthesis of Novel Polycyclic Pyrrolo[2,1-a]isoquinolines Bearing Indeno[1,2-b]quinoxaline Moieties by a Three-Component [3+2]-Cycloaddition Reaction

Synlett ◽  
2019 ◽  
Vol 31 (03) ◽  
pp. 267-271 ◽  
Author(s):  
Firouz Matloubi Moghaddam ◽  
Atiyeh Moafi ◽  
Behzad Jafari ◽  
Alexander Vilinger ◽  
Peter Langer
Keyword(s):  
Cycloaddition Reaction ◽  
Reaction Times ◽  
Dipolar Cycloaddition ◽  
Diastereoselective Synthesis ◽  
X Ray Diffraction ◽  
Reaction Conditions ◽  
One Pot ◽  
Three Component Reaction ◽  
Relative Stereochemistry ◽  
High Yields

A regio- and diastereoselective synthesis of 2,3-dihydro-10b′H-spiro[indeno[1,2-b]quinoxaline-11,1′-pyrrolo[2,1-a]isoquinoline]-2′,3′-diylbis(phenylmethanone) derivatives containing four contiguous chiral stereocenters was achieved through 1,3-dipolar cycloaddition of isoquinolinium N-ylides in a one-pot three-component reaction. The desired products were obtained in short reaction times and in moderate to high yields (up to 92%) under relatively mild reaction conditions. The structure and relative stereochemistry of the desired product was confirmed by X-ray diffraction analysis.

Ionic liquid-enabled synthesis, cholinesterase inhibitory activity, and molecular docking study of highly functionalized tetrasubstituted pyrrolidines

2018 ◽  
Vol 77 ◽  
pp. 263-268 ◽  
Author(s):  
Raju Suresh Kumar ◽  
Abdulrahman I. Almansour ◽  
Natarajan Arumugam ◽  
Dhaifeallah Mohammed Qaide Althomili ◽  
Mohammed Altaf ◽  
...  
Keyword(s):  
Ionic Liquid ◽  
Molecular Docking ◽  
Inhibitory Activity ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Cholinesterase Inhibitory Activity

A Simple, One-Pot Synthesis of Trans-Substituted Spiro [5,5] undecane-1,5,9-triones with Aromatic Aldehydes and Meldrum's Acid as the Starting Materials

2015 ◽  
Vol 68 (10) ◽  
pp. 1599 ◽  
Author(s):  
Jingping Ou-Yang ◽  
Yu Zhao ◽  
Huailei Jiang ◽  
Lingxin Meng ◽  
Xingshu Li ◽  
...  
Keyword(s):  
1H Nmr ◽  
Aromatic Aldehydes ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Meldrum's Acid ◽  
X Ray Diffraction ◽  
Meldrum’S Acid ◽  
Reaction Conditions ◽  
One Pot ◽  
X Ray

A simple, one-pot process for the construction of substituted spiro[5,5]undecane-1,5,9-triones using aromatic aldehydes and Meldrum’s acid, and aniline as a catalyst, is reported. Fifteen compounds were synthesized, and the trans/cis ratios were calculated based on 1H NMR analyses of the unpurified products. Quantum mechanical calculations and X-ray diffraction were undertaken to identify the configuration of compound 2a. The proposed mechanisms for these reactions are presented in this paper. In contrast to previous literature, this method endows excellent diastereoselectivity to a series of trans-substituted derivatives. The method is characterized by its simple operation, commercial availability of all materials, mild reaction conditions and moderate-to-good chemical yields.

scholarly journals Design, Construction, and Characterization of a New Regioisomer and Diastereomer Material Based on the Spirooxindole Scaffold Incorporating a Sulphone Function

Symmetry ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1337 ◽  
Author(s):  
Abdullah Mohammed Al-Majid ◽  
Saied M. Soliman ◽  
Matti Haukka ◽  
M. Ali ◽  
Mohammad Shahidul Islam ◽  
...  
Keyword(s):  
Chemical Shifts ◽  
Cycloaddition Reaction ◽  
X Ray Diffraction ◽  
One Pot ◽  
Catalyst Synthesis ◽  
X Ray ◽  
Reactivity Descriptors ◽  
Three Component Reaction ◽  
Hirshfeld Analysis ◽  
Donor Acceptor

The 1,3-dipolar cycloaddition reaction is one of the most rapid, and efficient protocols to access, and construct highly divergent heterocycle chiral auxiliaries. Free catalyst synthesis of spirooxindole scaffold incorporating sulphone moiety via one pot–three component reaction of 6-chloro-isatin, L-proline, and the phenylvinylsulphone as dienophile is presented. The new regioisomer and diastereomer was isolated by precipitation without the tedious purification step, and then characterized via NMR and single crystal X-ray diffraction analysis. Using Hirshfeld analysis, the analysis of molecular packing was performed. It depended mainly on strong O…H and N…H interactions, and weak H…H, C…H, and Cl…H interactions as well. DFT calculations were used to optimize the experimental X-ray structure, which was found well matched with the calculated one. Reactivity descriptors based on the energies of the highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbitals were calculated. Additionally, the donor–acceptor interactions which stabilized the system via σ–σ*, π→π*, n→σ* and n→π* electron delocalization processes were also computed using NBO calculations. The net interaction energies are 49.96, 235.38, 179.66 and 107.06 kJ/mol, respectively. Additionally, the calculated NMR chemical shifts correlated well with the experimental data (R2=0.99).

scholarly journals Cholinesterase Inhibition Activity and Molecular Docking Study of Eugenol Derivatives

2021 ◽  
Vol 50 (4) ◽  
pp. 1037-1045
Author(s):  
Khairunisa Mohd Zamli ◽  
Asnuzilawati Asari ◽  
Kooi Yeong Khaw ◽  
Vikneswaran Murugaiyah ◽  
Mariya al-Rashida ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Docking Simulation ◽  
Docking Study ◽  
Protein Docking ◽  
Cholinesterase Inhibition ◽  
Ache Inhibition ◽  
Molecular Docking Study ◽  
Ache Inhibitory Activity ◽  
Inhibition Property ◽  
Ellman’S Method

The study was conducted to explore the anticholinesterase inhibition property of eugenol derived molecules. Ten eugenol derivatives were synthesized and evaluated for the inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by Ellman’s method. Most of the tested derivatives showed higher inhibition on BChE than AChE, however, their overall inhibitory activity was weak. In contrast, three derivatives (compounds 3,6,9) showed higher and good AChE inhibitory activity of more than 50% inhibition at 10 μg/mL. Among them, compound 9bearing a ethyl substituent at para position of the benzoyl ring showed the most potent AChE inhibition, with IC50 of 5.64 μg/mL. Ligand-protein docking simulation was also performed for the most active derived molecules (compounds 3,6,9).

Water Promoted One-pot Three-Step Synthesis of Novel N-Saccharin Isoxazolines/Isoxazoles Using KI/Oxone Under Ultrasonic Activation

2019 ◽  
Vol 23 (11) ◽  
pp. 1270-1281 ◽  
Author(s):  
Hamza Tachallait ◽  
Mohsine Driowya ◽  
Eleuterio Álvarez ◽  
Rachid Benhida ◽  
Khalid Bougrin
Keyword(s):  
Cycloaddition Reaction ◽  
Hydroxylamine Hydrochloride ◽  
Spectroscopic Techniques ◽  
X Ray Diffraction ◽  
Ultrasonic Activation ◽  
One Pot ◽  
Ultrasonic Probe ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Compounds

A green and efficient regioselective protocol was developed for the preparation of novel isoxazolines and isoxazoles of N-saccharin derivatives via the water-promoted cycloaddition reaction of nitrile oxides with alkenes and alkynes. It is noteworthy that KI/Oxone/water-promoted one-pot three-component reactions of aldehyde, hydroxylamine hydrochloride, and alkene or alkyne were observed to be very satisfactory. The synthesis of all adducts (4a-j/5a-j) has been carried out by this method with high to excellent yields (70-95%) at 25°C within 30 min, using ultrasonic probe. All the new compounds were thoroughly characterized by spectroscopic techniques and also 5b, 5c and 5f were structurally identified by single-crystal X-ray diffraction methods. X-ray crystallography structure analysis clearly supported the regioselectivity of the cycloaddition reaction.

scholarly journals Synthesis, X-ray Single Crystal, Conformational Analysis and Cholinesterase Inhibitory Activity of a New Spiropyrrolidine Scaffold Tethered Benzo[b]Thiophene Analogue

Crystals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 120 ◽  
Author(s):  
Assem Barakat ◽  
Saied M. Soliman ◽  
Saeed Alshahrani ◽  
Mohammad Shahidul Islam ◽  
M. Ali ◽  
...  
Keyword(s):  
Single Crystal ◽  
Inhibitory Activity ◽  
Chemical Yield ◽  
Moderate Activity ◽  
One Pot ◽  
Topology Analysis ◽  
Standard Drug ◽  
X Ray ◽  
Cholinesterase Inhibitory Activity ◽  
Bond Network

Described herein is a one-pot protocol for the synthesis of a substituted spiropyrrolidine scaffold tethered benzo[b]thiophene analogue from (E)-3-(benzo[b]thiophen-2-yl)-1-(4-fluoro- phenyl)-prop-2-en-1-one. The described protocol has the advantage of the high purity of the cyclized adduct and high chemical yield. To assign the chemical structure, different spectrophotometric tools have been applied, including 1H-NMR, 13C-NMR, FTIR, and the X-ray single crystal technique. The X-ray structure showed that the studied compound exist in two disordered parts with equal partial occupancies. The energies of the two conformers were found to be very similar and not exceed 1 kcal/mol, which justifies their coexistence in the crystal with equal percentage. The molecular packing in the crystal was analyzed using Hirshfeld topology analysis. The packing described as two dimensional hydrogen bond network extended along the ac-plane in both conformers but the intermolecular interactions included in each conformer are not similar. The synthesized spiropyrrolidine scaffold tethered benzo[b]thiophene analogue was examined against cholinesterase inhibitory activity and show moderate activity compared to standard drug galantamine.

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