Synthesis of Urease Inhibitory 2, 4-bis
(4-cyanobenzyl)glycoluril using Sandmeyer Reaction and Density
Functional Theory Investigation

J 2021

Synthesis of Urease Inhibitory 2, 4-bis (4-cyanobenzyl)glycoluril using Sandmeyer Reaction and Density Functional Theory Investigation

YAWER, Mirza Arfan; Shehar BANO; Muhammad SALEEM; Affiefa YAWER; Riaz HUSSAIN et al.

Základní údaje

Originální název

Synthesis of Urease Inhibitory 2, 4-bis (4-cyanobenzyl)glycoluril using Sandmeyer Reaction and Density Functional Theory Investigation

Autoři

YAWER, Mirza Arfan; Shehar BANO; Muhammad SALEEM; Affiefa YAWER; Riaz HUSSAIN; Muhammad IMRAN; Ahmad IRFAN; Abdur RAUF a Tareq ABU-IZNEID

Vydání

Current organic synthesis, Sharjah, Bentham Science Publ Ltd, 2021, 1570-1794

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10401 Organic chemistry

Stát vydavatele

Spojené arabské emiráty

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.276

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/21:00124371

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

Glycoluril derivative; sandmeyer reaction; H-1 NMR; (HR-MS) mass spectrometry; urease enzyme; thiourea; IC50; density func-tional theory (DFT); bambusuril

Štítky

14313010, 143180, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 3. 2022 22:50, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

Aims: The aim of the present research was to synthesize glycoluril derivative 2,4-Bis(4cyanobenzyl)glycoluril through a convergent scheme. Background: For this purpose, Sandmeyer reaction procedure was employed for the synthesis of said compound. The structure of the pure compound was confirmed by using different spectroscopic techniques, such as 1HNMR, 13C-NMR and (HR-MS) Mass spectrometry. Objective: Convergent synthesis of 2,4-BIS (4-CYANOBENZYL)GLYCOLURIL USING SANDMEYER REACTION and urease inhibition study. Methods: The structure of the pure compound was confirmed by using different spectroscopic techniques such as 1H-NMR, 13C-NMR and (HR-MS) Mass spectrometry. The electronic properties of the newly synthesized compound and thiourea were determined by using density functional theory. Results: Furthermore, the compound was evaluated against urease enzyme and was found to be potent inhibitors with an IC50 value of 11.5 +/- 1.50 mu M when compared with standard inhibitor thiourea (IC50 = 21.0 +/- 1.90 mu M). The compound may serve as a lead compound to synthesize new cyano-based bambusuril in the future with enhanced biological properties. Conclusion: We have synthesized a new glycoluril derivative 2,4-Bis(4-cyanobenzyl)glycoluril by the sandmeyer reaction. It has been obtained in the form of light yellowish powder in good yield (96%). Glycoluril based macrocycles have been used in various fields; starting from the 2,4-Bis(4-nitrobenzyl)glycoluril (already reported compound), which has undergone reduction (CH3OH,Pt/C) , diazotization (NaNO2/HCl), cyanation (CuCl/KCN), respectively in order to synthesize the desired new glycoluril derivative. The obtained product will be used as a building block for the synthesis of the cyano based bambusuril marcocycle in the future. The yield of the obtained product has been monitored by using different amounts of cyanating reagent, but the best results are shown by the use of 4 mmol of CuCl/KCN. KCN with CuCl assisted the conversion of diazo group into the cyano group with enhanced yield when used in excess amount. It acts as a catalyst. The solubility characteristic of 2,4-Bis(4-cyanobenzyl)glycoluril has also been determined in different organic solvents. 1H NMR technique proved to be very helpful for the structure determination of our desired product. Benzylic protons give signals at 7.5 ppm and 7.8 ppm, respectively. The downfield peaks confirm the presence of CN group near the benzylic protons. Methine protons show a signal at 5.2 ppm, which ensures the basic skeleton of glycoluril. Ureidyl protons also confirm the synthesis of the heterocyclic 2,4-Bis(4-cyanobenzyl)glycoluril compound. The negative and positive electrostatic potential sites, molecular descriptors, and charge density distribution of frontier molecular orbitals are revealing that 4a with promising sites for electrophilic and nucleophilic attacks would result to enhance the urease inhibition, which is in good agreement with the experimental data.

Citovat

YAWER, Mirza Arfan; Shehar BANO; Muhammad SALEEM; Affiefa YAWER; Riaz HUSSAIN; Muhammad IMRAN; Ahmad IRFAN; Abdur RAUF a Tareq ABU-IZNEID. Synthesis of Urease Inhibitory 2, 4-bis (4-cyanobenzyl)glycoluril using Sandmeyer Reaction and Density Functional Theory Investigation. Current organic synthesis. Sharjah: Bentham Science Publ Ltd, 2021, roč. 18, č. 6, s. 592-597. ISSN 1570-1794. Dostupné z: https://doi.org/10.2174/1570179418666210113162909.

@article{1839330,
   author = {Yawer, Mirza Arfan and Bano, Shehar and Saleem, Muhammad and Yawer, Affiefa and Hussain, Riaz and Imran, Muhammad and Irfan, Ahmad and Rauf, Abdur and AbuandIzneid, Tareq},
   article_location = {Sharjah},
   article_number = {6},
   doi = {https://doi.org/10.2174/1570179418666210113162909},
   keywords = {Glycoluril derivative; sandmeyer reaction; H-1 NMR; (HR-MS) mass spectrometry; urease enzyme; thiourea; IC50; density func-tional theory (DFT); bambusuril},
   language = {eng},
   issn = {1570-1794},
   journal = {Current organic synthesis},
   title = {Synthesis of Urease Inhibitory 2, 4-bis (4-cyanobenzyl)glycoluril using Sandmeyer Reaction and Density Functional Theory Investigation},
   url = {https://www.eurekaselect.com/article/113286},
   volume = {18},
   year = {2021}
}

TY  - JOUR
ID  - 1839330
AU  - Yawer, Mirza Arfan - Bano, Shehar - Saleem, Muhammad - Yawer, Affiefa - Hussain, Riaz - Imran, Muhammad - Irfan, Ahmad - Rauf, Abdur - Abu-Izneid, Tareq
PY  - 2021
TI  - Synthesis of Urease Inhibitory 2, 4-bis (4-cyanobenzyl)glycoluril using Sandmeyer Reaction and Density Functional Theory Investigation
JF  - Current organic synthesis
VL  - 18
IS  - 6
SP  - 592-597
EP  - 592-597
PB  - Bentham Science Publ Ltd
SN  - 15701794
KW  - Glycoluril derivative
KW  - sandmeyer reaction
KW  - H-1 NMR
KW  - (HR-MS) mass spectrometry
KW  - urease enzyme
KW  - thiourea
KW  - IC50
KW  - density func-tional theory (DFT)
KW  - bambusuril
UR  - https://www.eurekaselect.com/article/113286
N2  - Aims: The aim of the present research was to synthesize glycoluril derivative 2,4-Bis(4cyanobenzyl)glycoluril through a convergent scheme. Background: For this purpose, Sandmeyer reaction procedure was employed for the synthesis of said compound. The structure of the pure compound was confirmed by using different spectroscopic techniques, such as 1HNMR, 13C-NMR and (HR-MS) Mass spectrometry. Objective: Convergent synthesis of 2,4-BIS (4-CYANOBENZYL)GLYCOLURIL USING SANDMEYER REACTION and urease inhibition study. Methods: The structure of the pure compound was confirmed by using different spectroscopic techniques such as 1H-NMR, 13C-NMR and (HR-MS) Mass spectrometry. The electronic properties of the newly synthesized compound and thiourea were determined by using density functional theory. Results: Furthermore, the compound was evaluated against urease enzyme and was found to be potent inhibitors with an IC50 value of 11.5 +/- 1.50 mu M when compared with standard inhibitor thiourea (IC50 = 21.0 +/- 1.90 mu M). The compound may serve as a lead compound to synthesize new cyano-based bambusuril in the future with enhanced biological properties. Conclusion: We have synthesized a new glycoluril derivative 2,4-Bis(4-cyanobenzyl)glycoluril by the sandmeyer reaction. It has been obtained in the form of light yellowish powder in good yield (96%). Glycoluril based macrocycles have been used in various fields; starting from the 2,4-Bis(4-nitrobenzyl)glycoluril (already reported compound), which has undergone reduction (CH3OH,Pt/C) , diazotization (NaNO2/HCl), cyanation (CuCl/KCN), respectively in order to synthesize the desired new glycoluril derivative. The obtained product will be used as a building block for the synthesis of the cyano based bambusuril marcocycle in the future. The yield of the obtained product has been monitored by using different amounts of cyanating reagent, but the best results are shown by the use of 4 mmol of CuCl/KCN. KCN with CuCl assisted the conversion of diazo group into the cyano group with enhanced yield when used in excess amount. It acts as a catalyst. The solubility characteristic of 2,4-Bis(4-cyanobenzyl)glycoluril has also been determined in different organic solvents. 1H NMR technique proved to be very helpful for the structure determination of our desired product. Benzylic protons give signals at 7.5 ppm and 7.8 ppm, respectively. The downfield peaks confirm the presence of CN group near the benzylic protons. Methine protons show a signal at 5.2 ppm, which ensures the basic skeleton of glycoluril. Ureidyl protons also confirm the synthesis of the heterocyclic 2,4-Bis(4-cyanobenzyl)glycoluril compound. The negative and positive electrostatic potential sites, molecular descriptors, and charge density distribution of frontier molecular orbitals are revealing that 4a with promising sites for electrophilic and nucleophilic attacks would result to enhance the urease inhibition, which is in good agreement with the experimental data.
ER  -

YAWER, Mirza Arfan; Shehar BANO; Muhammad SALEEM; Affiefa YAWER; Riaz HUSSAIN; Muhammad IMRAN; Ahmad IRFAN; Abdur RAUF a Tareq ABU-IZNEID. Synthesis of Urease Inhibitory 2, 4-bis (4-cyanobenzyl)glycoluril using Sandmeyer Reaction and Density Functional Theory Investigation. \textit{Current organic synthesis}. Sharjah: Bentham Science Publ Ltd, 2021, roč.~18, č.~6, s.~592-597. ISSN~1570-1794. Dostupné z: https://doi.org/10.2174/1570179418666210113162909.

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