Description
Ethyl 3,4-dihydroxybenzoate (EDHB) is an analogue of 2-oxoglutarate and thus a competitive inhibitor of prolyl hydroxylase domain enzymes (PHDs). It is known as protocatechuic acid and is present in plant foods such as olives, roselle, du-zhong, and white grape wine.This compound have antioxidant, cardioprotective, neuroprotective, antimicrobial, anti-inflammatory and myoprotective activity, as well as anti-ulcer activity[1].
Chemical Properties
pale yellow to beige crystalline powder
Uses
An antioxidant compound found in Sicilian virgin olive oils and red wines.
Uses
The compound is a prolyl 4-hydroxylase inhibitor and can be used to protect the myocardium.
Definition
ChEBI: An ethyl ester resulting from the formal condensation of the carboxy group of 3,4-dihydroxybenzoic acid with ethanol. It is the anti-oxidative component of peanut seed testa.
Biological Activity
Ethyl 3,4-dihydroxybenzoate (EDHB) contains reducible polyphenol hydroxyl groups and exhibits antioxidant activity. Recent studies have shown that EDHB acts as an analog of the substrate α-ketoglutarate and competes for prolyl-hydroxylase activity, thus acting as an inhibitor and effectively inhibiting collagen synthesis and breast cancer metastasis. In addition, in vitro and animal studies in a cerebral ischemic rat model have revealed that EDHB shows increased protective effects and improves rat behavior by inhibiting free radical damage[2].
Synthesis
General procedure for the synthesis of ethyl 3,4-dihydroxybenzoate from 3,4-dihydroxybenzoic acid and ethanol: 3,4-dihydroxybenzoic acid (5.0 g, 32.0 mmol) was placed in a round-bottomed flask, and 40 mL of anhydrous ethanol was added, and the temperature was slowly elevated to 40°C. The reaction was carried out in the following manner. Under stirring, 5 mL of concentrated sulfuric acid was added dropwise. After the dropwise addition, the reaction system was warmed up to 80 °C, and the reaction was kept at reflux for 10 hours. After completion of the reaction, the reaction solution was cooled to room temperature and the pH was adjusted to neutral with 10 M potassium hydroxide solution. Subsequently, the solvent was removed by distillation under reduced pressure and the resulting solid was washed with a small amount of cold water to afford the target product ethyl 3,4-dihydroxybenzoate. The product was a white solid in 89% yield.
References
[1] Charu Nimker. "Ethyl 3,4-dihydroxy benzoate, a unique preconditioning agent for alleviating hypoxia-mediated oxidative damage in L6 myoblasts cells." Journal of Physiological Sciences 65 1 (2015): 77–87.
[2] Bo Han. "A prolyl-hydroxylase inhibitor, ethyl-3,4-dihydroxybenzoate, induces cell autophagy and apoptosis in esophageal squamous cell carcinoma cells via up-regulation of BNIP3 and N-myc downstream-regulated gene-1." PLoS ONE (2014): e107204.
