Synthesis, Tautomerism, and Antiradical Activity of Novel Pteridinetrione Derivatives

Abstract

in Wiley Online Library (wileyonlinelibrary.com).Synthesis of 1-methyl-6-((2-(aryl-(heteryl-))-2-oxoethyl) pteridine-2,4,7(1H,3H,8H)-triones via [4 + 2]-cycloaddition of 1-methyl-5,6-diaminouracil with ethyl 4-aryl(heteryl)-2,4-dioxobutanoates is described in presented work. It was established that the reaction occurs regioselectively and proceeds under refluxing of starting compounds in acetic acid for 60 min. The structures of synthesized compounds were proven by complex of physicochemical methods including infrared, 1 H-, 13 C-NMR spectroscopy, liquid chromatographymass spectrometry, and electron impact-mass spectrometry. Based on the detail analysis of the correlational NMR spectral data (correlation spectroscopy, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, and Nuclear Overhauser effect spectroscopy), it was determined that in dimethyl sulfoxide solution, the 1-methyl-6-((2-(aryl-(heteryl-))-2-oxoethyl)pteridine-2,4,7(1H,3H,8H)-triones exist in two tautomeric forms: ketone (A) and enol (B). It was also found that tautomeric behavior of aforementioned compounds in hexadeuterated dimethyl sulfoxide is sensitive to the nature of the aryl or heteryl substituent at the position 6 of ring. The electron donating groups shift equilibrium to the tautomer A, while electron withdrawingto the tautomer B. The synthesized compounds were tested on antiradical activity. It was found that obtained compounds reveal radical scavenging activity comparable or higher than ascorbic acid.

Synthesis, antiradical, and antimicrobial activities of new pteridine‐2,4,7‐trione derivatives

“…Thus, it allowed to obtain a significant number of different biologically active agents. Reasonability of this direction was further confirmed by previously described antiradical effects of 6‐aryl (heteryl) substituted pteridine‐2,4,7‐triones …”

“…The band vibrations of C═O groups were absent in the IR spectra of compounds 2.1‐2.18 in contrast with the starting compounds 1.1‐1.18. In addition, wide bands of νCH─OH groups of exchanged protons were registered at the 3300 to 3150 cm −1 and CH─OH bonds' deformation vibrations at the 1315 to 1125 cm −1 , while compounds 3.1‐3.16 were characterized by deformation vibrations of the aryl (heteryl)ethenyl moiety at the 1310 to 1290 cm −1 and 980 to 960 cm −1 .…”

“…The modification of pteridinetrione derivatives containing a high‐reactive carbonyl moiety implies its reduction. As it was expected, compounds 1.1‐1.18 formed secondary alcohols 2.1‐2.18 with satisfactory yields (Scheme ).…”

“…Compounds 1.1‐1.18 , 4.1 and 5.1 were synthesized according to the described synthetic protocols . The other starting reagents and solvents were purchased from commercially available sources and were used without purification.…”

“…Scientific interest in the abovementioned class of compounds is caused by their high structural affinity to coenzymes as well as the possibility of their chemical modification . In this regard, the phenacyl‐containing 6‐(2‐R‐2‐oxoethyl)‐1‐methylpteridine‐2,4,7(1 H ,3 H ,8 H )‐triones are interesting chemical objects . The latter are flexible for structural modification because of the possibility of tautomeric transformations.…”