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 ethyl ester is a lipophilic derivative of ferulic acid, demonstrating increased ability to cross cell membranes. Ferulic acid ethyl ester has less antioxidant capacity than ferulic acid in neuronal PC12 cells (IC50 = 66.7 μM for ferulic acid ethyl ester vs. 44.6 μM for ferulic acid, 2,2-diphenyl-1-picrylhydrazyl radical scavenging). However, ferulic acid ethyl ester increases the expression of heme oxygenase-1, Hsp70, and Hsp72, providing neuroprotection against amyloid β-peptide. Moreover, ferulic acid ethyl ester (25 μM) completely prevents cytotoxicity induced by ultraviolet B irradiation of normal human epidermal melanocytes, again associated with an induced expression of heme oxygenase-1 and Hsp70.
To an ice-chilled suspension of trans-ferulic acid (1.942 g, 10 mmol, 1 eq) in absolute ethanol (20 mL) was added thionyl chloride (0.87 mL, 12 mmol, 1.2 eq). The resulting mixture was refluxed with stirring for 20 h. The solution was concentrated in vacuo, dissolved in ethyl acetate (30 mL) and washed with a 1 M HCI solution (15 mL), saturated NaHCOs solution (15 mL) and brine (15 mL). The organic layer was dried over anhydrous NajSC and concentrated in vacuo to afford Ethyl 4-hydroxy-3-methoxycinnamate as an orange oil (2.185 g, yield: 98%).
