Hesperetin is a flavonoid that has been found in citrus fruits and has diverse biological activities. It reduces ApoB protein levels, ACAT2 expression, and LDL degradation in HepG2 cells when used at a concentrations ranging from 10 to 200 μM. Hesperetin inhibits IgG-induced β-hexosaminidase release from RBL-2H3 cells (IC50 = 0.099 mg/ml). It inhibits LPS-induced nitric oxide (NO) production and reduces levels of inducible nitric oxide synthase (iNOS), IL-6, and IL-1β in BV-2 microglial cells. Hesperetin (5 mg/kg) inhibits passive cutaneous anaphylaxis in mice. It reduces body weight loss, colon shortening, and ulcer severity in a mouse model of TNBS-induced ulcerative colitis. Hesperetin reduces cortical and hippocampal neuronal apoptosis and increases time spent in the target quadrant in the Morris water maze in a mouse model of LPS-induced neuronal inflammation.
Beige to Light Brown Crystalline Solid
The aglucon of Hesperidin (H281185), a flavanone found in citrus fruits.
(±)-Hesperetin is an antioxidant flavonoid. Induces G1-phase cell cycle arrest. Anti-inflammatory. (±)-Hesperetin suppresses NF-κB activation. Reduces cholesterol biosynthesis. Inhibits lipid peroxidation. Neuroprotective against neuronal oxidative damage.
ChEBI: Hesperetin is a trihydroxyflavanone having the three hydroxy gropus located at the 3'-, 5- and 7-positions and an additional methoxy substituent at the 4'-position. It has a role as an antioxidant, an antineoplastic agent and a plant metabolite. It is a monomethoxyflavanone, a trihydroxyflavanone, a member of 3'-hydroxyflavanones and a member of 4'-methoxyflavanones. It is a conjugate acid of a hesperetin(1-).
Generic method: compound 2 was synthesized by the method reported in the literature. The raw material (S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-((((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-2-yl)oxy )benzodihydropyran-4-one (3.5 g, 5.7 mmol) was mixed with 10 mL of concentrated sulfuric acid in 280 mL of anhydrous methanol and the reaction was stirred at 60 °C for 7.5 hours. Upon completion of the reaction, 1.2 L of ethyl acetate was added to the reaction mixture and extracted at 20 °C. Subsequently, the organic phase was washed with 420 mL of water and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give a light yellow powdery crude product. The crude product was dissolved in 70 mL of acetone and then slowly added dropwise (over 60 minutes) to a pre-stirred 700 mL solution consisting of water and acetic acid mixed at 150:1 by volume, maintaining the temperature at 95°C. After dropwise addition, the mixed slurry was cooled to 45°C, the product was collected by filtration and dried under vacuum.
Crystallise it from EtOAc or ethanol. The natural S(-) form crystallises from EtOH and has m 216-218o and [] D -37.6o (c 2, EtOH). Note that C2 is chiral. [Beilstein 18 II 204, 18 III/IV 3215, 18/5 V 214.]
[1] Journal of Medicinal Chemistry, 2011, vol. 54, # 1, p. 95 - 106
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[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 23, p. 7194 - 7197
[4] Patent: CN105693682, 2016, A. Location in patent: Paragraph 0024; 0025
[5] Journal of Chemical Research, 2014, vol. 38, # 7, p. 396 - 398
