scholarly journals Design, Microwave-Assisted Synthesis and In Silico Prediction Study of Novel Isoxazole Linked Pyranopyrimidinone Conjugates as New Targets for Searching Potential Anti-SARS-CoV-2 Agents

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6103
Author(s):  
Faisal K. Algethami ◽  
Maher Cherif ◽  
Salma Jlizi ◽  
Naoufel Ben Ben Hamadi ◽  
Anis Romdhane ◽  
...  

A series of novel naphthopyrano[2,3-d]pyrimidin-11(12H)-one containing isoxazole nucleus 4 was synthesized under microwave irradiation and classical conditions in moderate to excellent yields upon 1,3-dipolar cycloaddition reaction using various arylnitrile oxides under copper(I) catalyst. A one-pot, three-component reaction, N-propargylation and Dimroth rearrangement were used as the key steps for the preparation of the dipolarophiles3. The structures of the synthesized compounds were established by 1H NMR, 13C NMR and HRMS-ES means. The present study aims to also predict the theoretical assembly of the COVID-19 protease (SARS-CoV-2 Mpro) and to discover in advance whether this protein can be targeted by the compounds 4a–1 and thus be synthesized. The docking scores of these compounds were compared to those of the co-crystallized native ligand inhibitor (N3) which was used as a reference standard. The results showed that all the synthesized compounds (4a–l) gave interesting binding scores compared to those of N3 inhibitor. It was found that compounds 4a, 4e and 4i achieved greatly similar binding scores and modes of interaction than N3, indicating promising affinity towards SARS-CoV-2 Mpro. On the other hand, the derivatives 4k, 4h and 4j showed binding energy scores (−8.9, −8.5 and −8.4 kcal/mol, respectively) higher than the Mpro N3 inhibitor (−7.0 kcal/mol), revealing, in their turn, a strong interaction with the target protease, although their interactions were not entirely comparable to that of the reference N3.

Synlett ◽  
2019 ◽  
Vol 31 (03) ◽  
pp. 267-271 ◽  
Author(s):  
Firouz Matloubi Moghaddam ◽  
Atiyeh Moafi ◽  
Behzad Jafari ◽  
Alexander Vilinger ◽  
Peter Langer

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.


Catalysts ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 185
Author(s):  
Ivy L. Librando ◽  
Abdallah G. Mahmoud ◽  
Sónia A. C. Carabineiro ◽  
M. Fátima C. Guedes da Silva ◽  
Carlos F. G. C. Geraldes ◽  
...  

A set of Cu(I) complexes with 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo-[3.3.1]nonane (DAPTA) phosphine ligands viz. [CuX(κP-DAPTA)3] (1: X = Br; 2: X = I) and [Cu(μ-X)(κP-DAPTA)2]2 (3: X = Br; 4: X = I) were immobilized on activated carbon (AC) and multi-walled carbon nanotubes (CNT), as well as on these materials after surface functionalization. The immobilized copper(I) complexes have shown favorable catalytic activity for the one-pot, microwave-assisted synthesis of 1,2,3-triazoles via the azide-alkyne cycloaddition reaction (CuAAC). The heterogenized systems with a copper loading of only 1.5–1.6% (w/w relative to carbon), established quantitative conversions after 15 min, at 80 °C, using 0.5 mol% of catalyst loading (relative to benzyl bromide). The most efficient supports concerning heterogenization were CNT treated with nitric acid and NaOH, and involving complexes 2 and 4 (in the same order, 2_CNT-ox-Na and 4_CNT-ox-Na). The immobilized catalysts can be recovered and recycled by simple workup and reused up to four consecutive cycles although with loss of activity.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Mohammed Aarjane ◽  
Siham Slassi ◽  
Bouchra Tazi ◽  
Amina Amine

A simple and mild protocol towards the synthesis of new 1,2,3-triazole compounds derived from acridone has been developed via regiospecific 1,3-dipolar cycloaddition reaction between 10-(prop-2-yn-1-yl)acridone derivatives and aromatic azides using CuI as a catalyst. The cycloaddition reaction has been performed using conventional as well as microwave-assisted methods. Microwave-assisted synthesis caused a significant reduction in the reaction times and improvement in the yields of all the synthesized compounds compared with the conventional method. The structure of the 1,4-disubstituted 1,2,3-triazoles has been elucidated by IR, HRMS, 1H-NMR, 13C-NMR, and 2D NMR (1H-13C HMBC, 1H-1H COSY, and 1H-1H NOESY) spectroscopies.


2019 ◽  
Vol 70 (9) ◽  
pp. 3094-3099 ◽  
Author(s):  
Emilian Georgescu ◽  
Florea Dumitrascu ◽  
Florentina Georgescu ◽  
Constantin Draghici ◽  
Denisa Dumitrescu

A library of new pyrrolo[1,2-c]quinazoline derivatives was obtained by the one-pot, three-component microwave-assisted synthesis, starting from quinazolines, 2-bromoacetyl derivatives and electron-deficient alkynes in 1,2-epoxybutane via 1,3-dipolar cycloaddition of quinazolinium N-ylides. This synthetic pathway offers a simple and rapid access to a large range of pyrrolo[1,2-c]quinazoline derivatives.


RSC Advances ◽  
2015 ◽  
Vol 5 (25) ◽  
pp. 19724-19733 ◽  
Author(s):  
Shaik Karamthulla ◽  
Md. Nasim Khan ◽  
Lokman H. Choudhury

An expeditious one-pot, metal-free, three-component reaction of arylglyoxals, cyclic 1,3-dicarbonyls and 2-aminopyridines in the presence of molecular iodine under microwave irradiation is reported.


2011 ◽  
Vol 89 (10) ◽  
pp. 1236-1244 ◽  
Author(s):  
Kancherla Rajesh ◽  
Bandapalli Palakshi Reddy ◽  
Vijayaparthasarathi Vijayakumar

The one pot, three component reaction of p-hydroxy benzaldehyde, β-ketoester, and ammonium acetate afforded the corresponding monopodal 1,4-dihydropyridines as building blocks, which in turn converted into diversified novel bipodal, tripodal, and tetrapodal 1,4-dihydropyridines with different alkylating agents through conventional as well as microwave assisted reactions. The unambiguous structural confinements of the all the synthesized compounds were drawn out with the help of 2D NMR (H-H COSY and C-H COSY).


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