Regioselective Oxidative Coupling of 4-Hydroxystilbenes:  Synthesis of Resveratrol and ε-Viniferin (E)-Dehydrodimers

Abstract

Treatment of 5-[2-(4-hydroxyphenyl)vinyl]benzene-1,3-diol (resveratrol) with an equimolar amount of silver(I) acetate in dry MeOH at 50 degrees C for 1 h followed by chromatographic purification with a short silica gel column allowed the isolation of its (E)-dehydrodimer, 5-[5-[2-(3,5-dihydroxyphenyl)vinyl]-2-(4-hydroxyphenyl)-2,3-dihydrobenzofuran-3-yl]benzene-1,3-diol, as a racemic mixture in high yield. The present method was applicable to the oxidative dimerization of 4-hydroxystilbenes such as trans-styrylphenol and 5-[6-hydroxy-2-(4-hydroxyphenyl)-4-[2-(4-hydroxyphenyl)vinyl]-2,3-dihydrobenzofuran-3-yl]benzene-1,3-diol (epsilon-viniferin) leading to the corresponding 2-(4-hydroxyphenyl)-2,3-dihydrobenzofurans possessing various types of biological activities.

Laccase‐Catalyzed Dimerization of Hydroxystilbenes

“…The results of these two experiments clearly supported our hypothesis that the reaction proceeded through radical-radical coupling and not through the radical addition to the double bond of a non-radical substrate. These results were in accordance with most of the literature reports [8,9] and not with the hypothesis suggested by Penning and co-workers, who proposed a mechanism in which the resveratrol dimerization occurs via radical attack to a second molecule of resveratrol. [14] …”

“…[7] More recently, Sako described the non-enzymatic synthesis of 2 involving the treatment of 1 with AgOAc and other metallic oxidants. [8] Similarly, Takaya and co-workers described FULL PAPERS the treatment of 1 with several oxidizing reagents and found that TlA C H T U N G T R E N N U N G (NO 3 ) 3 and K 3 [Fe(CN) 6 ] were the best oxidants to transform 1 into 3, whereas FeCl 3 in acetone and MnO 2 in dichloromethane were the best catalysts to produce the dimer 2. [9] Different studies have shown that resveratrol is transformed in vivo (for instance by incubating 1 with Botrytis cinerea cultures) into various oxidized products (dimers), such as 2.…”

“…Synthesis of trans-3,5-Dihydroxy-4'-methoxystilbene (8) [28c] a) 3,5-Diisopropoxybenzaldehyde: Isopropyl bromide (3.1 mL, 4.5 equivs.) and then anhydrous potassium carbonate (3.3 g, 3.3 equivs.)…”

Total Synthesis of Resveratrol‐Based Natural Products: A Chemoselective Solution

“…[6][7][8][9][10][11] Typically, mixtures of compounds were observed [6][7][8] and, in those rare instances when selectivity was achieved, solely nonnatural products resulted. [9,10] Thus far, only a highly engineered resveratrol fragment has proven capable of leading to an actual dimeric natural product within this class. [11] Given this state of affairs, we wondered if a structural solution might exist for this general chemoselectivity problem, one empowered by the identification of hidden relationships between their seemingly divergent architectures.…”

Synthesis, modeling and biological studies on 4-2'(2, 3- dihydrobenzofuranyl) coumarins

“…[1][2][3][4][5][6] Recently 2,3-dihydrobenzofuran-5-ol has been shown to be more promising than vitamin E2 in inhibition of lipid per oxidation. 7 This skeleton has been a part of number of naturally occurring oxygen heterocycles.…”