520-33-2

Basic information

• Product Name: HESPERETIN
• Synonyms: 5,7,3'-TRIHYDROXY-4'-METHOXYFLAVANONE;4'-METHOXY-3',5,7-TRIHYDROXYFLAVANONE;(+/-)-3',5,7-TRIHYDROXY-4'-METHOXYFLAVANONE;3',5,7-TRIHYDROXY-4'-METHOXYFLAVANONE;3',5,7-TRIHYDROXY-4-METHOXYFLAVANONE;2,3-DIHYDRO-5,7-DIHYDROXY-2S-(3-HYDROXY-4-METHOXPHENYL)-4H-1-BENZOPYRAN-4-ONE;HESPERETINE;(+/-)-HESPERETIN
• CAS NO: 520-33-2
• Molecular Formula: C₁₆H₁₄O₆
• Molecular Weight: 302.28
• EINECS: 208-290-2
• Product Categories: Flavanones;Biochemistry;Flavonoids;Natural Plant Extract;Inhibitors;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;natural product
• Mol File: 520-33-2.mol
• Article Data: 41

Chemical Properties

• Melting Point: 230-232°C
• Boiling Point: 363.32°C (rough estimate)
• Flash Point: 223 °C
• Appearance: Beige to Light Brown Crystalline Solid
• Density: 1.2514 (rough estimate)
• Vapor Pressure: 2.45E-14mmHg at 25°C
• Refractive Index: -4 ° (C=1.8, EtOH)
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 7.49±0.40(Predicted)
• Water Solubility: Soluble in water (partly), dilute alkalis, and ethanol (50 mg/ml).
• Merck: 14,4670
• BRN: 309850
• CAS DataBase Reference: HESPERETIN(CAS DataBase Reference)
• NIST Chemistry Reference: HESPERETIN(520-33-2)
• EPA Substance Registry System: HESPERETIN(520-33-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39-27-37
• WGK Germany: 3
• Hazardous Substances Data: 520-33-2(Hazardous Substances Data)

Usage

Description

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.

Uses

Different sources of media describe the Uses of 520-33-2 differently. You can refer to the following data:
1. The aglucon of Hesperidin (H281185), a flavanone found in citrus fruits.
2. antiallergic
3. (±)-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.

Definition

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-).

Purification Methods

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.]

InChI:InChI=1/C16H14O6/c1-21-13-3-2-8(4-10(13)18)14-7-12(20)16-11(19)5-9(17)6-15(16)22-14/h2-6,14,17-19H,7H2,1H3/t14-/m0/s1

Synthetic route

hesperidin (520-26-3) → hesperetin (520-33-2)

Conditions	Yield
With sulfuric acid; acetic acid In water for 12h; Reflux;	98%
With sulfuric acid In water at 121℃; for 4h; High pressure;	87%
With sulfuric acid In ethanol for 8h; Reflux;	87%

7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5) + hesperidin (520-26-3) → 4-methylumbelliferyl-rutinoside (1356391-89-3) + hesperetin (520-33-2)

Conditions	Yield
With water In dimethyl sulfoxide at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;	A 28% B n/a

hesperidin (520-26-3) → hesperetin (520-33-2) + 3′,5,7,8-tetrahydroxy-4′-methoxyflavanone

Conditions	Yield
With Aspergillus saitoi In water; dimethyl sulfoxide at 30℃; pH=5.0;	A n/a B 3.5%

hesperidin (520-26-3) → (S)-2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-benzopyrone (520-33-2) + hesperetin (520-33-2)

Conditions	Yield
With sulfuric acid; ethylene glycol
With sulfuric acid
With methanol; sulfuric acid

hesperidin (520-26-3) → D-Glucose (2280-44-6) + L-rhamnose (73-34-7) + hesperetin 7‐O‐β‐D‐glucopyranoside + hesperetin (520-33-2)

Conditions	Yield
With sulfuric acid In water at 140℃; for 1h; Kinetics; Product distribution; Further Variations:; pH-values; Reagents; Temperatures; Hydrolysis;

hesperidin (520-26-3) → hesperetin-7-glucoside + hesperetin (520-33-2)

Conditions	Yield
L. acidophilus NCC 3010 crude extract for 4 - 8h; pH=4 - 6; Product distribution / selectivity; Enzymatic reaction;
L. plantarum NCC 1313 crude extract for 4 - 8h; pH=4 - 6; Product distribution / selectivity; Enzymatic reaction;

4G-α-D-glucopyranosyl hesperidin (161713-86-6) → hesperidin (520-26-3) + hesperetin (520-33-2)

Conditions	Yield
With small intestine homogenate of rat at 37℃; for 4h; Title compound not separated from byproducts.;

concentrated H2 SO4 + hesperidin (520-26-3) → hesperetin (520-33-2)

Conditions	Yield
In methanol; water

(S)-2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-benzopyrone (520-33-2) → (R)-4'-methoxy-3',5,7-trihydroxyflavanone (24604-97-5) + hesperetin (520-33-2)

Conditions	Yield
With ammonium acetate In water; isopropyl alcohol pH=5; Resolution of racemate;
With per(4-chloro-3-methyl)phenylcarbamate β-cyclodextrin clicked onto an alkynyl surface modified silica support In ethanol; hexane at 25℃; Resolution of racemate;

methanol (67-56-1) + hesperidin (520-26-3) → C13H24O10 (184239-14-3) + hesperetin (520-33-2)

Conditions	Yield
With water at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;

propan-1-ol (71-23-8) + hesperidin (520-26-3) → C15H28O10 (168172-05-2) + hesperetin (520-33-2)

Conditions	Yield
With water at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;

ethanol (64-17-5) + hesperidin (520-26-3) → ethyl α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (187539-57-7) + hesperetin (520-33-2)

Conditions	Yield
With water at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;

2-methyl-propan-1-ol (78-83-1) + hesperidin (520-26-3) → C16H30O10 + hesperetin (520-33-2)

Conditions	Yield
With water at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;

pentan-1-ol (71-41-0) + hesperidin (520-26-3) → C17H32O10 (189187-99-3) + hesperetin (520-33-2)

Conditions	Yield
With water at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;

isopropyl alcohol (67-63-0) + hesperidin (520-26-3) → C15H28O10 (1174639-57-6) + hesperetin (520-33-2)

Conditions	Yield
With water at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;

hesperidin (520-26-3) → rutinose (26184-96-3, 552-74-9, 47235-47-2, 56906-86-6, 56942-81-5, 59246-67-2, 68398-81-2, 68567-48-6, 68567-49-7, 75828-90-9) + hesperetin (520-33-2)

Conditions	Yield
With water at 60℃; for 0.5h; pH=5; aq. buffer; Enzymatic reaction;
With ethanol; α-rhamnosyl-β-glucosidase at 30℃; for 2h; Enzymatic reaction;
With α-rhamnosyl-β-glucosidase; water Enzymatic reaction;
With sulfuric acid In methanol; water for 6h; Reflux;
With 6-O-α-rhamnosyl-β-glucosidase from Acremonium sp. DSM24697; choline chloride; urea In aq. phosphate buffer at 60℃; for 1h; pH=6; Reagent/catalyst; Enzymatic reaction;

hesperidin (520-26-3) + benzyl alcohol (100-51-6) → 1′-O-benzyl-α-L-rhamnopyranosyl-(1″→6′)-β-D-glucopyranoside (88510-10-5) + hesperetin (520-33-2)

Conditions	Yield
With water at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;

hesperidin (520-26-3) + butan-1-ol (71-36-3) → n-butyl α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside + hesperetin (520-33-2)

Conditions	Yield
With water at 30℃; for 1h; pH=5; aq. buffer; Enzymatic reaction;

hesperetin 7‐O‐β‐D‐glucopyranoside → β-D-glucose (492-61-5) + hesperetin (520-33-2)

Conditions	Yield
With water Enzymatic reaction;

hesperidin (520-26-3) → 6-O-α-L-rhamnopyranosyl-β-D-glucopyranose (552-74-9, 26184-96-3, 47235-47-2, 56906-86-6, 56942-81-5, 68398-81-2, 68567-48-6, 68567-49-7, 75828-90-9, 59246-67-2) + hesperetin (520-33-2)

Conditions	Yield
With solid phase supported Acremonium sp. DSM24697 α-rhamnosyl-β-glucosidase at 60℃; for 1h; pH=5; Kinetics; aq. buffer; Enzymatic reaction;

neohesperidin (13241-33-3, 61303-28-4, 61303-29-5, 61303-30-8, 61347-97-5, 61348-24-1, 88294-38-6, 139686-38-7) → 2-O-α-L-rhamnopyranosyl-β-D-glucopyranose (19949-48-5) + hesperetin (520-33-2)

Conditions	Yield
With sulfuric acid In methanol; water for 6h; Reflux;

hesperetin 7‐O‐β‐D‐glucopyranoside → hesperetin (520-33-2)

Conditions	Yield
With β-D-glucosidase In aq. buffer at 50 - 100℃; for 0.583333h; pH=4; Kinetics; Enzymatic reaction;

S-adenosyl-L-methionine (485-80-3, 15519-60-5, 60018-85-1, 60018-86-2, 79845-28-6) + eriodictyol (552-58-9) → hesperetin (520-33-2)

Conditions	Yield
With DL-dithiothreitol; recombinant Plagiochasma appendiculatum flavone 6-O-methyltransferase; magnesium chloride In aq. buffer at 37℃; for 0.5h; pH=7.5; Enzymatic reaction;

hesperetin (520-33-2) → diosmetin (520-34-3)

Conditions	Yield
With pyridine; iodine at 90℃; for 22h;	100%
With iodine In pyridine at 90℃; for 8h;	85%
With pyridine; iodine at 90 - 95℃;
With trifluoroacetic anhydride; potassium iodide In dimethyl sulfoxide; N,N-dimethyl-formamide at 100 - 120℃; for 4h; Temperature; Reagent/catalyst;	37.6 g

1-deoxy-1-fluoro-α-D-glucose (2106-10-7) + hesperetin (520-33-2) → hesperetin 7-α-O-glucoside

Conditions	Yield
With α-glucosidase from sulfolobus solfataricus In dimethyl sulfoxide at 45℃; for 2h; pH=9; Enzymatic reaction;	99%

temozolomide (85622-93-1) + hesperetin (520-33-2) → C6H6N6O2*C16H14O6

Conditions	Yield
In ethanol for 1h;	94%

tert-butyldimethylsilyl chloride (18162-48-6) + hesperetin (520-33-2) → 3',5,7-tri-O-tert-butyldimethylsilylhesperetin

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; silylation;	89%

2-Hydroxybenzoylhydrazine (936-02-7) + hesperetin (520-33-2) → hesperetin (2-hydroxybenzoyl)hydrazone (1261060-91-6)

Conditions	Yield
With acetic acid In ethanol for 24h; Reflux;	83.6%

benzenesulfonic acid (98-11-3) + hesperetin (520-33-2) → (2S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-7-yl benzenesulfonate

Conditions	Yield
With sodium carbonate; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 100℃; for 6h;	80.9%

hesperetin (520-33-2) → 3-(3-hydroxy-4-methoxy-phenyl)-1-(2,4,6-trihydroxyphenyl)propan-1 -one (35400-60-3)

Conditions	Yield
With potassium hydroxide; hydrogen; palladium on activated charcoal at 30℃; under 2280 Torr; for 0.5h;	80%

formaldehyd (50-00-0) + 4-(2-(piperazin-1-yl)ethyl)morpholine (4892-89-1) + hesperetin (520-33-2) → 6-[4-(2-morpholin-4-ylethyl)piperazine-1-yl]methyl-3',5,7-trihydroxyflavanone

Conditions	Yield
In methanol; water for 0.5h; Mannich Aminomethylation;	80%

o-trifluoromethylbenzyl bromide (395-44-8) + hesperetin (520-33-2) → (S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-{[2-(trifluoromethyl)benzyl]oxy}chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	80%

4-ethylpiperazine (5308-25-8) + formaldehyd (50-00-0) + hesperetin (520-33-2) → C23H28N2O6

Conditions	Yield
In methanol; water for 0.5h; Mannich Aminomethylation;	79%

formaldehyd (50-00-0) + tert-butylamine (75-64-9) + hesperetin (520-33-2) → C21H25NO6

Conditions	Yield
In methanol; water for 0.5h; Mannich Aminomethylation;	78%

formaldehyd (50-00-0) + phenethylamine (64-04-0) + hesperetin (520-33-2) → C25H25NO6

Conditions	Yield
In methanol; water for 0.5h; Mannich Aminomethylation;	78%

4-Fluorobenzyl bromide (459-46-1) + hesperetin (520-33-2) → (S)-7-[(4-fluorobenzyl)oxy]-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	78%

1-bromomethyl-3-trifluoromethylbenzene (402-23-3) + hesperetin (520-33-2) → (S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-{[3-(trifluoromethyl)benzyl]oxy}chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	78%

4-bromomethyltrifluoromethylbenzene (402-49-3) + hesperetin (520-33-2) → (S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-{[4-(trifluoromethyl)benzyl]oxy}chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	77%

propyl bromide (106-94-5) + hesperetin (520-33-2) → (S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-propoxychroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	75%

1-(Bromomethyl)-3-fluorobenzene (456-41-7) + hesperetin (520-33-2) → (S)-7-[(3-fluorobenzyl)oxy]-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	75%

2-methylbenzyl bromide (89-92-9) + hesperetin (520-33-2) → (S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-[(2-methylbenzyl)oxy]chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	74%

formaldehyd (50-00-0) + isopropylamine (75-31-0) + hesperetin (520-33-2) → C20H23NO6

Conditions	Yield
In methanol; water for 0.5h; Mannich Aminomethylation;	73%

4-Methylbenzyl bromide (104-81-4) + hesperetin (520-33-2) → (S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-[(4-methylbenzyl)oxy]chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	73%

o-fluorobenzyl bromide (446-48-0) + hesperetin (520-33-2) → (S)-7-[(2-fluorobenzyl)oxy]-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	72%

benzyl bromide (100-39-0) + hesperetin (520-33-2) → (S)-7-(benzyloxy)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one (1403990-90-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	71%
With potassium carbonate In acetone at 56℃; for 10.5h;	70.1%

1-methyl-piperazine (109-01-3) + formaldehyd (50-00-0) + hesperetin (520-33-2) → C22H26N2O6

Conditions	Yield
In methanol; water for 0.5h; Mannich Aminomethylation;	70%

ethyl bromoacetate (105-36-2) + hesperetin (520-33-2) → 7-O-(2-ethoxy-2-oxoethyl)hesperetin

Conditions	Yield
With potassium carbonate; potassium iodide In ethanol for 1h; Reflux;	70%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.333333h;	68%
With potassium carbonate; potassium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 0.5h;	50%
Stage #1: hesperetin With potassium carbonate; potassium hydrogencarbonate In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: ethyl bromoacetate In N,N-dimethyl-formamide for 1h;	50%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.333333h;

4-cyanobenzyl bromide (17201-43-3) + hesperetin (520-33-2) → (S)-4-{[(5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-7-yl)oxy]methyl}benzonitrile

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	70%

C35H56O5 (1186389-76-3) + hesperetin (520-33-2) → C51H68O10 (1314678-14-2)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 60℃; for 2.5h; Inert atmosphere;	68%

ethyl crotonate (10544-63-5) + hesperetin (520-33-2) → C22H22O8

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 1h;	68%

1-(2-hydroxyethyl)piperazine (103-76-4) + formaldehyd (50-00-0) + hesperetin (520-33-2) → C23H28N2O7

Conditions	Yield
In methanol; water for 0.5h; Mannich Aminomethylation;	67%

1-bromomethyl-3-methyl-benzene (620-13-3) + hesperetin (520-33-2) → (S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-[(3-methylbenzyl)oxy]chroman-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Alkaline conditions;	67%

Upstream product

• 520-26-3 hesperidin 
• 161713-86-6 4^G-α-D-glucopyranosyl hesperidin 
• 67-56-1 methanol 
• 71-23-8 propan-1-ol 
• 90-33-5 7-hydroxy-4-methyl-chromen-2-one 
• 64-17-5 ethanol 
• 78-83-1 2-methyl-propan-1-ol 
• 71-41-0 pentan-1-ol 
• 67-63-0 isopropyl alcohol 
• 100-51-6 benzyl alcohol 
• 71-36-3 butan-1-ol 
• 13241-33-3 neohesperidin 
• 485-80-3 S-adenosyl-L-methionine 
• 552-58-9 eriodictyol 

Downstream Products

• 70987-96-1 5-hydroxy-3′4′7-trimethoxy flavanone 
• 520-33-2 (S)-2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-benzopyrone 
• 6274-73-3 (S)-5,7-diacetoxy-2-(3-acetoxy-4-methoxy-phenyl)-chroman-4-one 
• 6033-54-1 (-)-hesperetin oxime 
• 75917-11-2 5-hydroxy-6,3',4'-trimethoxyflavanone 
• 211255-69-5 5,7,3'-trihydroxydihydroquercetin 3-acetate 4'-(methyl ether) 
• 3162-05-8 3',5,7-triacetoxy-4'-methoxyflavone 
• 6274-73-3 3',5,7-triacetoxy-4'-methoxyflavanone 
• 5928-45-0 5,3′-dihydroxy-7,4′-dimethoxyflavanone 
• 6033-54-1 (+/-)-hesperetin oxime 
• 76799-48-9 3',5-dihydroxy-4'-methoxy-7-(2-butyrolactonoxy)flavanone 
• 76799-53-6 3',5-dihydroxy-4'-methoxy-7-<2-ethoxy>flavanone 
• 128373-93-3 Acetic acid 5-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-4-oxo-chroman-7-yl ester 
• 128373-92-2 Acetic acid 5-(5,7-dihydroxy-4-oxo-chroman-2-yl)-2-methoxy-phenyl ester 

Relevant articles and documents

Discovery of Novel Bacterial Chalcone Isomerases by a Sequence-Structure-Function-Evolution Strategy for Enzymatic Synthesis of (S)-Flavanones

Chalcone isomerase (CHI) is a key enzyme in the biosynthesis of flavonoids in plants. The first bacterial CHI (CHIera) was identified from Eubacterium ramulus, but its distribution, evolutionary source, substrate scope, and stereoselectivity are still unclear. Here, we describe the identification of 66 novel bacterial CHIs from Genbank using a novel Sequence-Structure-Function-Evolution (SSFE) strategy. These novel bacterial CHIs show diversity in substrate specificity towards various hydroxylated and methoxylated chalcones. The mutagenesis of CHIera according to the substrate binding models of these novel bacterial CHIs resulted in several variants with greatly improved activity towards these chalcones. Furthermore, the preparative scale conversion catalyzed by bacterial CHIs has been performed for five chalcones and revealed (S)-selectivity with up to 96 % ee, which provides an alternative biocatalytic route for the synthesis of (S)-flavanones in high yields.

Enhanced antioxidant, anti-inflammatory and α-glucosidase inhibitory activities of citrus hesperidin by acid-catalyzed hydrolysis

Hesperidin hydrolysates (HHS) was produced by the hydrolysis of hesperidin (HDN) in previous studies. The potential components in HHS were identified by LC-MS, and minor components (MCS) in HHS were isolated. Antioxidant activities by radical-scavenging capacities, reducing capacity and β-carotene-linoleate assay, anti-inflammatory effects by inhibiting NO production of RAW 264.7 cells, and α-glucosidase inhibitory effects of HDN, HHS, MCS and henperetin (HTN) were investigated in present study. HHS showed higher radical scavenging activities, higher reducing capacity, and higher inhibitory activity in the β-carotene-linoleate assay than HDN. HHS inhibited the production of NO and pro-inflammatory cytokines of RAW 264.7 cells more strongly than HDN. HHS also intensively inhibited α-glucosidase activity whereas HDN showed little activity. In addition, the effects of MCS on above activities showed it play a synergistic part with HTN. This work suggested that hydrolyzation of HDN enhance the activities, and provided valuable information on effective utilization of HDN.

Synthesis of 5-Hydroxy-3′,4′,7-trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2-Mediated Anticancer Drug Resistance

3′,4′,7-Trimethoxyflavone (TMF) has been reported to show a potent reversal effect on drug resistance mediated by breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we designed and synthesized five derivatives with either a hydroxy group or a fluorine atom at C-5 and several kinds of capping moiety at the C-7 hydroxy group, on the same 3′,4′-dimethoxy-substituted flavone skeleton. We subsequently evaluated the efficacies of these compounds against BCRP-expressing human leukaemia K562/BCRP cells. Reversal of drug resistance was expressed as the concentration of compound causing a twofold reduction in drug sensitivity (RI50). Of the synthesized compounds, the reversal effect of 5-hydroxy-3′,4′,7-trimethoxyflavone (HTMF, RI50 7.2 nm) towards 7-ethyl-10-hydroxycamptothecin (SN-38) was stronger than that of TMF (RI50 18 nm). Fluoro-substituted 5-fluoro-3′,4′,7-trimethoxyflavone (FTMF, RI50 25 nm) and monoglycosylated 7-(β-glucosyloxy)-5-hydroxy-3′,4′-dimethoxyflavone (GOHDMF, 91 nm) also exhibited reversal effects, whereas the di- and triglycoside derivatives did not. TMF, HTMF and FTMF at 0.01–10 μm upregulated the K562/BCRP cellular accumulation of Hoechst 33342 nuclear staining dye. In addition, western blotting revealed that treatment of K562/BCRP cells with 0.1 μm TMF, HTMF or FTMT suppressed the expression of BCRP. HTMF showed the strongest inhibition of BCRP-mediated efflux and suppression of BCRP expression of the three effective synthesized flavones.