Chemoselective Esterification of Phenolic Acids and Alcohols

Appendino, Giovanni; Minassi, Alberto; Daddario, Nives; Bianchi, Federica; Tron, Gian Cesare

doi:10.1021/ol0266471

Cited by 92 publications

(82 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…General Synthetic Procedure for Polyphenolic Acid Ester Derivatives The esters were synthesized from polyphenolic acid and 2-phenoxy ethanol by Mitsunobu esterification using DIAD and TPP as coupling reagents 28) as shown in Fig. 1.…”

mentioning

confidence: 99%

Evaluation of Polyphenolic Acid Esters as Potential Antioxidants

Hsu

Lin

Hsu

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Six polyphenolic acid esters were synthesized and their antioxidative properties were evaluated in three model systems [2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, 2,2-azobis(2-amidinopropane)dihydrochloride (AAPH)-induced lipid peroxidation system, and the dye-bleaching assay of peroxynitrite radical]. Among these compounds, we found that compounds 4 [3,4-dihydroxy-benzoic acid-(2-phenoxyethyl ester)], and 5 [3,4-dihydroxy-cinnamic acid-(2-phenoxyethyl ester)] provided comparable activity to caffeic acid phenethyl ester (CAPE) in the DPPH model. Compound 3 [2,5-dihydroxy-benzoic acid-(2-phenoxyethyl ester)], was found to be more active than CAPE in the AAPH system, it also displayed about 2-fold greater activity than CAPE in the peroxynitrite radical model. These results suggest that these phenolic acid ester derivatives, with their potent anti-oxidant activities, may have useful applications as antioxidants.Key words polyphenolic acid ester; caffeic acid analogue; antioxidant; free radical scavenging activity

show abstract

mentioning

confidence: 99%

Evaluation of Polyphenolic Acid Esters as Potential Antioxidants

Hsu

Lin

Hsu

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Under basic catalysis, phenols can be easily deprotonated, so the esterification of phenolic alcohols and phenolic acids via acyl nucleophilic substitution requires previous protection of the phenolic hydroxyl groups, due to the competition between aliphatic and phenolic hydroxyl groups (Appendino et al, 2002;Gambacorta et al, 2007).…”

Section: Synthetic Approachesmentioning

confidence: 99%

“…Synthesis of hydroxytyrosyl acetate via benzylation of phenolic hydroxyls A two-step procedure involving the reaction of methyl orthoformate-protected hydroxytyrosol with acetyl chloride, and hydrolytic deprotection in phosphate buffer under very mild conditions (pH=7.2) to get hydroxytyrosyl acetate (87% overall yield) (Scheme 3) was also described as a successful procedure for the preparation of HT-derived esters (Gambacorta et al, 2007 In order to overcome the problems associated to the protection and deprotection steps of the phenolic hydroxyl groups, different methods for the preparation of hydroxytyrosyl esters by reaction of hydroxytyrosol with various acylating agents have been described, such as esterification with free acids (Appendino et al, 2002), transesterification with methyl or ethyl esters (Alcudia et al, 2004;Trujillo et al, 2006), acyl chlorides (Torregiani et al, 2005) and the use of enzymatic methodologies (Grasso et al, 2007;Mateos et al, 2008;Torres de Pinedo et al, 2005;Buisman, 1998).…”

Section: Protection Of Phenolic Hydroxyl Groupsmentioning

confidence: 99%

“…The Mitsunobu reaction has been also applied to the chemoselective esterification of phenolic acids with phenolic alcohols (Appendino et al, 2002) as demonstrated by the condensation of hydroxytyrosol with gallic acid, and of vanillyl alcohol with caffeic acid in a one step procedure with 48% and 50% yields, respectively. The esterification is carried out using DIAD (diisopropyl azodicarboxylate) and TPP (triphenylphosphine) in THF (Scheme 6).…”

Section: Esterification With Free Acids: Mitsunobu Esterificationmentioning

confidence: 99%

See 1 more Smart Citation

Biological Properties of Hydroxytyrosol and Its Derivatives

Fernandez‐Bolanos¹,

López²,

López-García³

et al. 2012

Olive Oil - Constituents, Quality, Health Properties and Bioconversions

View full text Add to dashboard Cite

“…Although the synthesis via acid chloride was straightforward, a one-step esterification in which acids react directly with alcohol is practical because of the troublesome protection and deprotection steps. The recent study by Appenedino et al 26) indicated that the Mitsunobu reaction is especially suitable for the esterification of phenolic acids and alcohols. Because phenolic carbons are not substrates for the SN2-type reaction, the Mitsunobu reaction shows good chemoselectivity between hydroxyl groups bound to aliphatic and aromatic carbons.…”

Section: Synthesis Of Selenium-containing Polyphenolic Acid Esters Anmentioning

confidence: 99%

Synthesis of Selenium-Containing Polyphenolic Acid Esters and Evaluation of Their Effects on Antioxidation and 5-Lipoxygenase Inhibition

Lin

Chang

Chiang³

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Free radicals are highly reactive molecules generated predominantly during cellular respiration and normal metabolism. Imbalance between the cellular production of free radicals and the ability of cells to defend against them is referred to as oxidative stress (OS). Biological systems use enzymatic (superoxide dismutase, glutathione peroxidase, etc.) and nonenzymatic (uric acid, creatinine, polyamine, retinal, etc.) antioxidant systems to prevent OS. However, once the systems are disturbed the uncontrolled oxidative stresses initiate a series of harmful biochemical events or generate them as a consequence of earlier tissue injury, thus aggravating the final damages. Such damages include brain dysfunction, cancer, and cardiovascular disease and inflammation. 1,2) Selenium is an essential trace element and has been known to be intimately involved in the activity of enzymes such as glutathione peroxidase (GSH Px) and thioredoxin reductase, which catalyze chemistry essential to the protection of biomolecules against OS and free radical damage.3) Although possessing potent antioxidative activity, like other protein drugs GSH Px is limited for clinical use due to the instability and immunogenicity of the endogenous forms. To circumvent the intrinsic difficulties of using natural enzymes as drugs, several attempts have been made to produce synthetic compounds that mimic the properties of GSH Px. Ebselen, 4) 2-phenylbenzisoselenazole-3(2H)-one, was the most successful compound and showed anti-inflammatory, anti-atherosclerotic, and cytoprotective activities. These biological activities are attributed partly to the strong tendency of selenium to undergo redox reactions. Therefore, in the design of novel antioxidants as therapeutic agents there are a number of approaches utilizing the redox properties of selenium and incorporating selenium into the molecule skeleton. Review articles have summarized the synthesis and properties of a considerable number of organoselenium compounds prepared as potential pharmaceuticals. 5-7)Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE, 1; Fig. 1), a kind of polyphenolic acid, is an active component of propolis from honeybee hives. It has antiviral, anti-inflammatory, and immunomodulatory properties 8) and has been shown to inhibit the growth of different types of transformed cells. [8][9][10][11][12][13] In transformed cells, CAPE alters the redox state and induces apoptosis.14) It has been reported that CAPE suppresses lipid peroxidation, 15) displays antioxidant activity, 16) and inhibits ornithine decarboxylase, protein tyrosine kinase (PTK), and lipoxygenase activities. [17][18][19][20] CAPE can also inhibit phorbol ester-induced H 2 O 2 production and tumor promotion. 21,22) In recent years, studies in our laboratory have been directed at synthetic antioxidants with diverse anti-oxidative functionalities. [23][24][25] Based on the unique anti-oxidative properties of selenium, we speculated that ester analogues of polyphenolic acid and phenylselenoethanol, such as 2 ...

show abstract

Chemoselective Esterification of Phenolic Acids and Alcohols

Abstract: [formula: see text] The Mitsunobu reaction can distinguish between alcohol and phenol hydroxyls in esterification reactions, providing an expeditious and broadly applicable entry into various phenolics and polyphenolics of biomedical and nutritional relevance.

Cited by 92 publications

References 21 publications

Evaluation of Polyphenolic Acid Esters as Potential Antioxidants

Evaluation of Polyphenolic Acid Esters as Potential Antioxidants

Biological Properties of Hydroxytyrosol and Its Derivatives

Synthesis of Selenium-Containing Polyphenolic Acid Esters and Evaluation of Their Effects on Antioxidation and 5-Lipoxygenase Inhibition

Contact Info

Product

Resources

About