Efficient Electrocatalytic Approach to Spiro[Furo[3,2-b]pyran-2,5′-pyrimidine] Scaffold as Inhibitor of Aldose Reductase

Michail N Elinson,Fedor V Ryzhkov,Yuliya E Ryzhkova,Artem N Fakhrutdinov,Anatoly N Vereshchagin,Mikhail P Egorov

doi:10.3390/electrochem2020021

Michail N Elinson, Fedor V Ryzhkov + Show 4 more

Open Access

https://doi.org/10.3390/electrochem2020021

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Abstract

A continuously growing interest in convenient and ‘green’ reaction techniques encourages organic chemists to elaborate on new synthetic methodologies. Nowadays, organic electrochemistry is a new useful method with important synthetic and ecological advantages. The employment of an electrocatalytic methodology in cascade reactions is very promising because it provides the combination of the synthetic virtues of the cascade strategy with the ecological benefits and convenience of electrocatalytic procedures. In this research, a new type of the electrocatalytic cascade transformation was found: the electrochemical cyclization of 1,3-dimethyl-5-[[3-hydroxy-6-(hydroxymethyl)-4-oxo-4H-pyran-2-yl](aryl)methyl]pyrimidine-2,4,6(1H,3H,5H)-triones was carried out in alcohols in an undivided cell in the presence of sodium halides with the selective formation of spiro[furo[3,2-b]pyran-2,5′-pyrimidines] in 59-95% yields. This new electrocatalytic process is a selective, facile, and efficient way to create spiro[furo[3,2-b]pyran-2,5′-pyrimidines], which are pharmacologically active heterocyclic systems with different biomedical applications. Spiro[furo[3,2-b]pyran-2,5′-pyrimidines] were found to occupy the binding pocket of aldose reductase and inhibit it. The values of the binding energy and Lead Finder’s Virtual Screening scoring function showed that the formation of protein–ligand complexes was favorable. The synthesized compounds are promising for the inhibition of aldose reductase. This makes them interesting for study in the treatment of diabetes or similar diseases.

Highlights

C–H acids are well-known and useful starting compounds for electrocatalytic transformations using alkali metal halides as mediators [9,10,11,12,13]
Electrocatalytic reactions of heterocyclic C–H acids [17] have been intensively studied, as they afford the synthesis of different classes of heterocyclic compounds with a wide range of bioactivity [18]
At the beginning of our study, MeOH was used as a solvent and alkali metal bromides were used as mediators

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. C–H acids are well-known and useful starting compounds for electrocatalytic transformations using alkali metal halides as mediators [9,10,11,12,13]. Electrocatalytic reactions of heterocyclic C–H acids [17] have been intensively studied, as they afford the synthesis of different classes of heterocyclic compounds with a wide range of bioactivity [18]. In continuation of our research on electrocatalytic cascade transformations of carbonyl compounds and C–H acids into different types of spirocyclic compounds [36,37,38,39,40], and taking into consideration the biomedical applications of spirocyclic barbiturates given above, we were prompted to design a facile and efficient electrocatalytic one-pot cascade methodology for the conversion of 1,3-dimethyl-5-[[3-hydroxy-6-(hydroxymethyl)-4oxo-4H-pyran-2-yl](aryl)methyl]pyrimidine-2,4,6(1H,3H,5H)-triones 1 into spiro[furo[3,2b]pyran-2,50 -pyrimidines] 2

Experimental Section

Discussion

Electrocatalytic

(Supplementary

The general view of compound

Conclusions