Uses
Ferulic acid is a hydroxycinnamic acid that is abundant in plants and originally derived from giant fennel (F. communis). This naturally-occurring phenolic has antioxidant activities that provide protection against inflammation and cancer. Ferulic acid methyl ester is a lipophilic derivative of ferulic acid, demonstrating increased ability to cross cell membranes. Ferulic acid methyl ester has less antioxidant capacity than ferulic acid in neuronal PC12 cells (IC50 = 74.7 μM for ferulic acid ethyl ester vs. 44.6 μM for ferulic acid, 2,2-diphenyl-1-picrylhydrazyl radical scavenging). Ferulic acid methyl ester, at 10-25 μg/ml, inhibits the release of pro-inflammatory cytokines, blocks the expression of COX-2, and reduces nitric oxide generation from LPS-stimulated macrophages.
Synthesis
General procedure for the synthesis of methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate from methanol and 3-methoxy-4-hydroxyphenylacrylic acid: ferulic acid (1.94 g, 10 mmol) was dissolved in anhydrous methanol (3.20 g, 100 mmol), and 0.25 mL of concentrated sulfuric acid was added as catalyst. The reaction was refluxed under stirring and the progress was monitored by thin layer chromatography (TLC). After the disappearance of the raw material point, the reaction was stopped and cooled to room temperature. The reaction mixture was poured into an ice-water system and the remaining acid was neutralized with a 10% excess of sodium carbonate solution. Subsequently, the reaction mixture was washed with saturated brine and extracted with ether. After separation of the organic phase, the organic layers were combined and dried over anhydrous sodium sulfate. After filtration to remove the desiccant, the solvent was evaporated under reduced pressure to give the crude product. The crude product was eluted with hexane and further purified by recrystallization to afford (E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid methyl ester in the form of a white solid with a mass of 1.42 g (theoretical mass 2.08 g) in 68.3% yield.
References
[1] European Journal of Medicinal Chemistry, 2009, vol. 44, # 1, p. 332 - 344
[2] Chinese Chemical Letters, 2014, vol. 25, # 3, p. 474 - 478
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 19, p. 6085 - 6088
[4] Molecular Crystals and Liquid Crystals, 2016, vol. 624, # 1, p. 59 - 68
[5] Organic and Biomolecular Chemistry, 2009, vol. 7, # 11, p. 2367 - 2377
