Stéphane Quideau

Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis†

Eating five servings of fruits and vegetables per day! This is what is highly recommended and heavily advertised nowadays to the general public to stay fit and healthy! Drinking green tea on a regular basis, eating chocolate from time to time, as well as savoring a couple of glasses of red wine per day have been claimed to increase life expectancy even further! Why? The answer is in fact still under scientific scrutiny, but a particular class of compounds naturally occurring in fruits and vegetables is considered to be crucial for the expression of such human health benefits: the polyphenols! What are these plant products really? What are their physicochemical properties? How do they express their biological activity? Are they really valuable for disease prevention? Can they be used to develop new pharmaceutical drugs? What recent progress has been made toward their preparation by organic synthesis? This Review gives answers from a chemical perspective, summarizes the state of the art, and highlights the most significant advances in the field of polyphenol research.

Identification and synthesis of new ferulic acid dehydrodimers present in grass cell walls

Seven isomeric dehydrodimers of ferulic acid (4-hydroxy-3-methoxycinnamic acid) have been synthesized and identified in extracts of saponified cell walls of cocksfoot, switchgrass, and suspension-cultured corn. Dehydrodimers (E,E)-4,4′-dihydroxy-5,5′-dimethoxy-3,3′-bicinnamic acid, trans-5-[(E)-2-carboxyvinyl]-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid, (Z)-β-{4-[(E)-2-carboxyvinyl]-2-methoxyphenoxy}-4-hydroxy-3-methoxycinnamic acid, (E)-3-{4-[(E)-2-carboxyvinyl]-2-methoxyphenoxy}-4-hydroxy-5-methoxycinnamic acid, (E,E)-4,4′-dihydroxy-3,5′-dimethoxy-β,3′-bicinnamic acid, 4,4′-dihydroxy-3,3′-dimethoxy-β,β′-bicinnamic acid, and trans-7-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-6-methoxy-1,2-dihydronaphthalene-2,3-dicarboxylic acid, all arise from oxidative coupling of ferulate esters in cell walls and represent products of 8–5, 8–8, 8–O–4, 4–O–5, and 5–5 radical coupling. Prior literature has acknowledged only the presence of the 5–5-coupled dehydrodimer (E,E)-4,4′-dihydroxy-5,5′-dimethoxy-3,3′-bicinnamic acid. Consequently, by measuring only a single dehydrodimer and assuming inappropriate response factors, ferulate dehydrodimers have been underestimated by factors of up to 20. Synthetic routes to all seven isomers have been developed to provide structural authentication and determination of GC response factors.

Lignin–feruloyl ester cross-links in grasses. Part 1. Incorporation of feruloyl esters into coniferyl alcohol dehydrogenation polymers

Methyl 5-O-(E)-[γ-13C]feruloyl-α-L-arabinofuranoside (FA-Ara) has been synthesized and incorporated into a synthetic lignin dehydrogenation polymer (DHP) of coniferyl alcohol. Inverse-detected long-range C–H correlation NMR experiments on the DHP lignin gave correlation peaks indicative of the copolymerization of the FA-Ara and coniferyl alcohol into the DHP polymer. The bonding sites and modes, as determined by analysis of the carbonyl region of the long-range C–H correlated 2D NMR experiment, are predictable from free-radical coupling mechanisms. In addition to the abundant 4-O-α′ and 4-O-β′ ether couplings, structures involving the β-position of the feruloyl moiety of FA-Ara in β-ether, phenylcoumaran and pinoresinolide structures were present. The incorporation of feruloyl esters into a lignin DHP results in some structures which would not release ferulic acid by solvolytic schemes currently used for quantitation of ferulic acid in plant materials. Thus the degree to which hydroxycinnamic acids are involved in the lignification of forages may be significantly underestimated.

SYNTHETIC USES OF ORTHOQUINONE MONOKETALS AND THEIR ORTHOQUINOL VARIANTS. A REVIEW

(1999). SYNTHETIC USES OF ORTHOQUINONE MONOKETALS AND THEIR ORTHOQUINOL VARIANTS. A REVIEW. Organic Preparations and Procedures International: Vol. 31, No. 6, pp. 617-680.

Highly Diastereoselective Synthesis of Orthoquinone Monoketals through λ3-Iodane-Mediated Oxidative Dearomatization of Phenols†

Orthoquinone monoketals A and orthoquinols B are cyclohexa-2,4-dienone derivatives with valuable reactivity features for the construction of complex molecular architectures. Their conjugated dienone unit and the vicinal positioning of their oxygenated functionalities constitute a unique structural arrangement that can be transformed rapidly into various kinds of polyoxygenated (poly)cyclic systems (Scheme 1).

Identification of the Lipophilic Factor Produced by Macrophages That Stimulates Steroidogenesis1

Macrophages are known to release a lipophilic factor that stimulates testosterone production by Leydig cells. This macrophage-derived factor (MDF) is thought to be physiologically relevant, because removal of macrophages from the testis results in altered testosterone secretion and reduced fertility. The purpose of the present study was to purify this factor, elucidate its chemical structure, and determine whether it is both present in the testis and acts when injected intratesticularly. Culture media from testicular and peritoneal macrophages were extracted with ether, and the organic phase was sequentially purified on C18, silica, and cyano-HPLC columns. MDF was detected using a rat Leydig cell bioassay, with testosterone secretion being the end point. Purified material and crude ether extracts were analyzed by gas chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy. The time of elution of MDF from both testicular and peritoneal macrophages was identical on all three HPLC column...

Chemistry and biology of ellagitannins : an underestimated class of bioactive plant polyphenols

Ellagitannins Renewed the Concept of Tannin (T Okuda et al.) Structural Diversity and Antimicrobial Activities of Ellagitannins (T Yoshida et al.) Biosynthesis of Ellagitannins: Old Ideas and New Solutions (G Gross) Physicochemical Properties and Biomimetic Reactions of Ellagitannins (T Tanaka et al.) Total Synthesis of Ellagitannins (K Khanbabaee) Immunomodulatory Ellagitannin Chemistry (K Feldman et al.) Bioavailability and Metabolism of Ellagic Acid and Ellagitannins (F A Tomas-Barberan et al.) Ellagitannins in Food (R Torronen) C-Glycosidic Ellagitannins and Their Influence on Wine Chemistry (S Quideau et al.).

2-Alkoxyarenol-derived orthoquinols in carbon–oxygen, carbon–nitrogen and carbon–carbon bond-forming reactions

Abstract Silylated oxygen- and nitrogen-tethered orthoquinol acetates, generated by phenyliodine(III) diacetoxy-mediated oxidative acetoxylation of 2-alkoxyphenols in CH2Cl2 can be used to furnish regioselectively benzannulated heterocycles. Oxidative activation of 2-alkoxynaphthols with non-nucleophilic phenyliodine(III) bis(trifluoroacetoxy) in the presence of carbon nucleophiles, including oxidation sensitive silyl enol ethers, constitute a potentially valuable route to naturally occurring vicinally oxygenated benz[a]anthracene motifs.

Total Synthesis of Wasabidienones B1 and B0 via SIBX-Mediated Hydroxylative Phenol Dearomatization

The first total synthesis of the natural nondimerizing o-quinol (+)-wasabidienone B1 was achieved from commercially available 1,3,5-trimethoxybenzene. The key dearomatizing transformation was efficiently accomplished via a hydroxylative phenol dearomatization reaction using the stabilized lambda(5)-iodane reagent IBX (SIBX). (+)-Wasabidienone B1 was then converted into its congener (-)-wasabidienone B0 via an improved thermally induced ring-contracting isomerization reaction.

A Biomimetic Route to Lignin Model Compounds via Silver (I) Oxide Oxidation. 1. Synthesis of Dilignols and Non-cyclic Benzyl Aryl Ethers

The oxidative coupling of (E)-coniferyl alcohol using 1.5 equiv. of silver (I) oxide in methylene Chloride led to the formation of ß-5-coupled dehydrodiconiferyl alcohol in 50% yjeld, whereas in l : l methylene Chloride: water solution, the ß-ß-coupled dehydrodimer pinoresinol was obtained äs the major reaction product in 25% yield. In aqueous (pH 5-8) and non-aqueous Solutions, the quinone methide generated by ß-O-4 coniferyl alcohol radical coupling rapidly led to the formation of significant amounts of the non-cyclic oc-O-4 benzyl aryl ethers; eryiÄw-guaiacylglycerol-a-dehydrodiconiferyl-ß-coniferyl-bisether, £ry//irö-guaiacylglycerol-a,ß-bis-coniferyl ether and eryf/zro-guaiacylglycerol-a-pinoresinol-ßconiferyl-bis-ether, via phenol addition. The addition of water became predominant only under acid catalysis. Non-cyclic benzyl alkyl ethers were not obtained. These findings, together with literature precedents, have implications for lignin biosynthesis.