Synthesis and Antioxidant Activity of Polyhydroxylated trans-Restricted 2-Arylcinnamic Acids

Abstract

A series of sixteen polyhydroxylated trans-restricted 2-arylcinnamic acid analogues 3a–p were synthesized through a one-pot reaction between homophthalic anhydrides and various aromatic aldehydes, followed by treatment with BBr3. The structure of the newly synthesized compounds was confirmed by spectroscopic methods and the configuration around the double bond was unequivocally estimated by means of gated decoupling 13C-NMR spectra. It was shown that the trans-cinnamic acid fragment incorporated into the target compounds’ structure ensures the cis-configuration of the stilbene backbone and prevents further isomerization along the carbon–carbon double bond. The antioxidant activity of compounds 3a–p was measured against 1,1-diphenyl-2-picrylhydrazyl (DPPH●), hydroxyl (OH●) and superoxide (O2●▬) radicals. The results obtained showed that the tested compounds possess higher activities than natural antioxidants such as protocatechuic acid, caffeic acid and gallic acid. Moreover, it was shown that a combination of two different and independently acting fragments of well-known pharmacological profiles into one covalently bonded hybrid molecule evoke a synergistic effect resulting in higher than expected activity. To rationalize the apparent antioxidant activity and to establish the mechanism of action, a SAR analysis and DFT quantum chemical computations were also performed.

3-(3,4-Dihydroxyphenyl)-8-hydroxy-2H-chromen-2-one

“…In a recent our articles, we demonstrated that polyhydroxylated cis-restricted stilbenes [8,9] or 3-arylcoumarins (2) bearing carboxylic function in their structure [10] can be obtained via one-pot procedure from diastereomeric mixture of methoxylated cis-and trans-3-aryl-3,4-dihydroisocoumarin-4-carboxylic acids [11] by treatment with BBr3. However, just recently we observed that replacement of BBr3 with HBr as a demethylating agent leads to a subsequent reaction, which produces decarboxylated 3-arylcoumarin derivative-the title compound 3 (Scheme 1).…”

“…Scheme 2) consisting of five sequential steps, including demethylation, lactone ring opening, elimination, isomerization, lactone ring closure and decarboxylation reactions. The main part of this mechanism was deduced on the base of our previous experiments (for details see [10]) and the starting diastereomeric mixture of cis-and trans-3-(2,3-dimethoxyphenyl)-6,7-dimethoxy-1-oxoisochroman-4-carboxylic acids (1) was obtained in 10 min from 6,7-dimetoxihomophthalic anhydride and 2,3-dimethoxybenzaldehyde in presence of DMAP/CH2Cl2 [8][9][10][11]. It has to be also mentioned that the target coumarin 3 was isolated in a high purity (>99%) and yield (92%) just by filtration at the end of the reaction, the latter suggesting the proposed reaction credible for the synthesis of a series of polyhydroxylated coumarin derivatives from readily available starting materials at a low cost.…”

Multifunctional biomolecules with roles in abiotic stress tolerance as well as nutraceutical potential

“…Substitution pattern of the flavonoids rings and hydrogen bond forces are proposed to play important roles in the antioxidant activity of flavonoids (Xiao et al 2008). Intermediates such as phenoxy radicals or phenoxide anion are involved in these activities (Mendoza-Wilson et al 2011). Miliovsky et al (2015 propose three important mechanisms may be involved in the radical-scavenging activities of phenolics; (1) single-electron transfer, associated with the O-H bond dissociation energy; (2) a two-step mechanism of ionization and proton transfer; (3) also a two-step mechanism of deprotonation and sequential electron transfer.…”

UV‐irradiation influence on free radical formation and radical scavenging ability of caffeic acid—EPR, UV‐Vis, and colorimetric examination

“…Fourier transform infrared (FTIR) and EPR spectroscopy were used to present antioxidant activity of caffeic acid in sunflower oil (Hamed & Allam, 2006). Antioxidant activity of caffeic acid against DPPH, hydroxyl (OH ● ), and superoxide (O 2 ● ) radicals was examined (Miliovsky et al, 2015). Schisandra chinensis leaves and fruits contained the valuable antioxidants ‐ polyphenols, especially caffeic acid (Mocan et al, 2014).…”

“…) radicals was examined (Miliovsky et al, 2015). Schisandra chinensis leaves and fruits contained the valuable antioxidants -polyphenols, especially caffeic acid (Mocan et al, 2014).…”