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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F21%3A00124371" target="_blank" >RIV/00216224:14310/21:00124371 - isvavai.cz</a>

Result on the web

<a href="https://www.eurekaselect.com/article/113286" target="_blank" >https://www.eurekaselect.com/article/113286</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570179418666210113162909" target="_blank" >10.2174/1570179418666210113162909</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Current organic synthesis

ISSN

1570-1794

e-ISSN

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Volume of the periodical

18

Issue of the periodical within the volume

6

Country of publishing house

AE - UNITED ARAB EMIRATES

Number of pages

6

Pages from-to

592-597

UT code for WoS article

000713714200005

EID of the result in the Scopus database

2-s2.0-85121251197