Ferulic acid ethyl ester

In search of novel natural antioxidant compounds that might posses a good brain bioavailability, our laboratory has focused attention on the phenolic compound ferulic acid ethyl ester (FAEE) (Fig. 18.1). Ferulic acid is a ubiquitous plant constituent that occurs primarily in seeds and leaves both in its free form and covalently linked to lignin and other biopolymers. Due to its phenolic nucleus and an extended side chain conjugation, it readily forms a resonance stabilized phenoxy radical that accounts for its potent antioxidant potential [Kanski et al., 2002 Kikuzaki et al., 2002], Ferulic acid has been shown to be protective against oxidative stress in vitro it is absorbed and excreted by humans, and may be a promising candidate for therapeutic intervention in AD [Yan et al., 2001]. Although ferulic acid has been demonstrated to be effective in vitro, the low lipophilicity impairs its in vivo efficiency, bioavailability, and stability. 

Joshi G, Perluigi M, Sultana R, Agrippino R, Calabrese V, Butterfield DA. 2006. In vivo protection of synaptosomes by ferulic acid ethyl ester (FAEE) from oxidative stress mediated by 2,2-azobis(2-amidino-propane)dihydrochloride (AAPH) or Fe(2 +)/ H(2jO(2) Insight into mechanisms of neuroprotection and relevance to oxidative stress-related neurodegenerative disorders. Neurochem Int 48 318-327. 

Perluigi M, Joshi G, Sultana R, Calabrese V, De Marco C, Coccia R, Cini C, Butterfield DA. 2006b. In vivo protective effects of ferulic acid ethyl ester against amyloid-beta peptide 1-42-induced oxidative stress. J Neurosci Res 84 418-426. 

Sultana R, Ravagna A, Mohmmad-Abdul H, Calabrese V, Butterfield DA. 2005. Ferulic acid ethyl ester protects neurons against amyloid beta-peptide(l-42)-induced oxidative stress and neurotoxicity Relationship to antioxidant activity. J Neurochem 92 749-758. 

On its own, DMD is too powerfnl an electrophilic reagent to be considered for lignin-retaining bleaching. Bnt, in carefnl conjunction with alkaline peroxide, it has been found useful in bleaching the ferulic acid-linked lignins in wheat straw mechanical pulps. Pan et al. [112] evaluated DMD for its ability to oxidize ferulic acid (IVa), ferulic acid ethyl ester and diferulic acid (IVb). All these model compounds were completely oxidized at room temperature. 

Esterases. Acetyl esterase (EC 3.1.1.6) removes acetyl esters from acetylated xylose and short-chain xylo-oligomers. It s polymeracting counterpart, acetyl xylan esterase (EC 3.1.1.72), has a similar activity, but prefers polymeric xylan.244 In addition to acetate-specific enzyme detection kits, HPLC or GC analysis of acetate release from native extracted xylan and chemically acetylated xylan, colorimetric substrates, such as p-nitrophenol acetate and /3-napthyl acetate, or the fluorometric substrate, 4-methylumbelliferyl acetate are also used to assay acetyl esterases.244,253 The third esterase, ferulic acid esterase (EC 3.1.1.73), hydrolyzes the ester bond between ferulic acid or coumaric acid and the arabinose side chain of arabinoxylan. Assays for this activity are usually carried out using starch-free wheat bran or cellulase-treated gramineous biomass as a substrate and monitoring ferulic or coumaric acid released by HPLC or TLC. When preparing enzyme-treated substrates, care must be taken to employ phenolic-acid-esterase-free cellulases.244 Other substrates include methyl and ethyl esters of the phenolic acids, as well as finely ground plant biomass.240,254,255... 

L-Phenylalanine,which is derived via the shikimic acid pathway,is an important precursor for aromatic aroma components. This amino acid can be transformed into phe-nylpyruvate by transamination and by subsequent decarboxylation to 2-phenylacetyl-CoA in an analogous reaction as discussed for leucine and valine. 2-Phenylacetyl-CoA is converted into esters of a variety of alcohols or reduced to 2-phenylethanol and transformed into 2-phenyl-ethyl esters. The end products of phenylalanine catabolism are fumaric acid and acetoacetate which are further metabolized by the TCA-cycle. Phenylalanine ammonia lyase converts the amino acid into cinnamic acid, the key intermediate of phenylpropanoid metabolism. By a series of enzymes (cinnamate-4-hydroxylase, p-coumarate 3-hydroxylase, catechol O-methyltransferase and ferulate 5-hydroxylase) cinnamic acid is transformed into p-couma-ric-, caffeic-, ferulic-, 5-hydroxyferulic- and sinapic acids,which act as precursors for flavor components and are important intermediates in the biosynthesis of fla-vonoides, lignins, etc. Reduction of cinnamic acids to aldehydes and alcohols by cinnamoyl-CoA NADPH-oxido-reductase and cinnamoyl-alcohol-dehydrogenase form important flavor compounds such as cinnamic aldehyde, cin-namyl alcohol and esters. Further reduction of cinnamyl alcohols lead to propenyl- and allylphenols such as... 

Unsaturated Lignin Model Compounds Double bonds in lignin model compounds are attacked by peracetate ions. Dehydro-di-woeugenol (XXI, Figure 12.9) reacted with epoxidation of the aliphatic double bond and formation of the diol. The double bonds in stilbenes [59] and coniferaldehyde [90] are also cleaved. FemUc acid (IVa) and its ethyl ester reacted slowly at 50°C the methyl ether, 3,4-dimethoxy cinnamic acid, was much less reactive and was almost quantitatively recovered [55]. The reactions of ferulic acid and its ethyl ester (both in the trans form) were accompanied by trans-cis isomerization, perhaps an indication of reversible phenoxy radical formation. HomovanilUc acid (XXXa) was also formed the proposed mechanism involved epoxidation of the a-P double bonds followed by decarboxylation. 

Experiments with tritium and C-labelled phenylalanine samples established that this amino-acid was incorporated intact as a Cg unit (with loss of C-1). Support for a pathway proceeding via cinnamic acid and hydroxylated derivatives and benzoylacetic acid derivatives was provided in further experiments with cinnamic acid, ferulic acid/isoferulic acid, and the (easily hydrolysed) ethyl esters of benzoylacetic acid and piperonylacetic acid. As far as they go the results suggest that a mixed pathway is in operation with introduction of hydroxy- and methylenedioxy-groups on more than one intermediate. 

Suberins or polyestolides are related to cutins. These are complex polymers composed of co-hydroxy monobasic acids linked by ester bonds. They also contain a,P-dibasic acids esterified with diols, as well as ferulic and sinapic acid moieties. Suberins are enriched with molecules having 16 and 18 carbon atoms. They also have ethyl-enic and hydroxyl functionalities, and ester and ether cross-linking can occur. 

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