Galloyl-Derived Orthoquinones as Reactive Partners in Nucleophilic Additions and Diels−Alder Dimerizations:  A Novel Route to the Dehydrodigalloyl Linker Unit of Agrimoniin-Type Ellagitannins

Abstract

Orthochloranil-mediated oxidation of galloyl monoethers furnishes the derived orthoquinones in excellent yield. These reactive electrophiles participate in a variety of nucleophilic addition reactions with heteroatomic and carbanionic partners. In addition, Lewis acid-mediated dimerization of the orthoquinones provides an efficient route to dehydrodigalloyl-type diaryl ether units characteristic of several ellagitannin natural products. The implications for ellagitannin biosynthesis and gallotannin-protein covalent attachment are discussed.

A unified strategy for the synthesis of highly oxygenated diaryl ethers featured in ellagitannins

“…One of the rare examples is Feldman's synthesis of DHDG derivative 3 (Fig. 2a) [19][20][21] . This synthesis is a four-step sequence that starts from orthoquinone 4 through (1) the self-hetero Diels-Alder cycloaddition of 4 to produce a mixture of regioisomers 5a and 5b, (2) b-elimination, as indicated by the curved arrows, (3) reduction of the orthoquinone, and (4) benzylation accompanying the Smiles rearrangement 22 , which converges the mixture into 3.…”

Oxidative Dimer Produced from a 2,3,4-Trihydroxybenzoic Ester

“…Oxidation mechanism studies on polyphenols have frequently used o-chloranil as an oxidant from a catechol to the corresponding quinone, since the reaction proceeds cleanly compared to using radical species. 12,13,19) Changing the oxidant from the DPPH radical to o-chloranil could simplify the chromatogram of the reaction mixture, probably due to the mild oxidative property of the nonradical chlorinated quinone compared to the DPPH radical. Hence, a distinctive new peak (t R ¼ 43:5 min) was observed in the equimolar reaction mixture of 4 and o-chloranil in acetonitrile at 5 min, as well as a broad peak (t R ¼ 23:6 min) detected at 400 nm.…”

“…The difference in total radical-scavenging efficiency of each hydroxybenzoic acid inherently depends on this latter phase, although little has been found for this complex stage. So far, a protocatechuic (3,4-dihydroxybenzoic) ester (1) gave its quinone dimer, 6) quinone acetal 7) and adducts, [8][9][10][11] and a gallic (3,4,5-trihydroxybenzoic) ester (2) and its analogs also produced quinone dimers 6,12,13) and adducts.12) In contrast to protocatechuic and gallic acids, there has been no report on the oxidation reaction of another naturally occurring phenolic acid, 2,3,4-trihydroxybenzoic acid (3).14-16) We have investigated the DPPH (2,2-diphenyl-1-picrylhydrazyl) radicalscavenging abilities and the oxidant-mediated reaction of 2,3,4-trihydroxybenzoic acid (3) and its ester (4) (Fig. 1), and identified a novel oxidative dimer in the reaction mixture with o-chloranil (3,4,5,6-tetrachloro-obenzoquinone) in acetonitrile.…”

“…The difference in total radical-scavenging efficiency of each hydroxybenzoic acid inherently depends on this latter phase, although little has been found for this complex stage. So far, a protocatechuic (3,4-dihydroxybenzoic) ester (1) gave its quinone dimer, 6) quinone acetal 7) and adducts, [8][9][10][11] and a gallic (3,4,5-trihydroxybenzoic) ester (2) and its analogs also produced quinone dimers 6,12,13) and adducts. 12) In contrast to protocatechuic and gallic acids, there has been no report on the oxidation reaction of another naturally occurring phenolic acid, 2,3,4-trihydroxybenzoic acid (3).…”

“…So far, a protocatechuic (3,4-dihydroxybenzoic) ester (1) gave its quinone dimer, 6) quinone acetal 7) and adducts, [8][9][10][11] and a gallic (3,4,5-trihydroxybenzoic) ester (2) and its analogs also produced quinone dimers 6,12,13) and adducts. 12) In contrast to protocatechuic and gallic acids, there has been no report on the oxidation reaction of another naturally occurring phenolic acid, 2,3,4-trihydroxybenzoic acid (3). [14][15][16] We have investigated the DPPH (2,2-diphenyl-1-picrylhydrazyl) radicalscavenging abilities and the oxidant-mediated reaction of 2,3,4-trihydroxybenzoic acid (3) and its ester (4) (Fig.…”