480-23-9

Usage

Uses

Used in Pharmaceutical Applications:
3',4',5,7-Tetrahydroxyisoflavone is used as a potential therapeutic agent for various health conditions due to its estrogenic and anti-estrogenic activities. It is being explored for its potential benefits in cardiovascular health, bone health, and the alleviation of menopausal symptoms.
Used in Nutraceutical Applications:
3',4',5,7-Tetrahydroxyisoflavone is used as a dietary supplement or functional food ingredient, capitalizing on its antioxidant properties and potential health benefits. It is often found in products that aim to support overall well-being and address specific health concerns related to hormonal balance and aging.
Used in Cosmetic Applications:
3',4',5,7-Tetrahydroxyisoflavone is used as an ingredient in skincare products for its antioxidant activity, which may help protect the skin from environmental damage and promote a more youthful appearance. It may also be included in formulations that target specific skin concerns related to aging and hormonal changes.

Synthetic route

3-(3,4-dimethoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one (53084-11-0) → orobol (480-23-9)

Conditions	Yield
With pyridine hydrochloride at 150℃; Inert atmosphere;	70%

3-(3',4'-dihydroxyphenyl)-5,7-dimethoxy-4H-chromen-4-one → orobol (480-23-9)

Conditions	Yield
With boron tribromide In dichloromethane at 60℃; for 18h;	10%

3-(3,4-dimethoxyphenyl)-5,7-dimethoxychromen-4-one (40316-84-5) → orobol (480-23-9)

Conditions	Yield
With hydrogen iodide; acetic anhydride at 150℃;

8-(β-D-glucopyranosyl)orobol (66026-81-1) → orobol (480-23-9)

Conditions	Yield
With hydrogen iodide; phenol Heating;	20 mg

6,8-di-C-β-D-glucopyranosyl-3',4',5,7-tetrahydroxyisoflavone (118949-94-3) → orobol (480-23-9)

Conditions	Yield
With hydrogen iodide; phenol Heating;	25 mg

Acetic acid 2-[2-(3,4-dihydroxy-phenyl)-3,3-dimethoxy-propionyl]-3,5-dihydroxy-phenyl ester → orobol (480-23-9)

Conditions	Yield
With hydrogenchloride In methanol for 2h; Heating; Yield given;

3',4',5,7-tetrahydroxyisoflavone β-D-glucopyranoside (20486-33-3) → orobol (480-23-9)

Conditions	Yield
With trifluoroacetic acid for 2h; Heating;

oroboside → orobol (480-23-9)

Conditions	Yield
With emulsin
With sulfuric acid

santal → orobol (480-23-9)

Conditions	Yield
With hydrogen iodide

2,2'-azobis-(2,4-dimethylvaleronitrile) (4419-11-8) + 5,7-Dihydroxy-3-(4-hydroxy-phenyl)-chromen-4-on (446-72-0) → orobol (480-23-9) + 2-[1-(5,7-dihydroxy-4-oxo-4H-chromen-3-yl)-4-oxo-cyclohexa-2,5-dienylperoxy]-2,4-dimethyl-pentanenitrile + 2-[1-(5,7-dihydroxy-4-oxo-4H-chromen-3-yl)-4-oxo-cyclohexa-2,5-dienyloxy]-4-hydroperoxy-2,4-dimethyl-pentanenitrile + 2-[1-(5,7-dihydroxy-4-oxo-4H-chromen-3-yl)-4-oxo-cyclohexa-2,5-dienylperoxy]-4-hydroperoxy-2,4-dimethyl-pentanenitrile

Conditions	Yield
In acetonitrile at 50℃; for 3h; Product distribution; Further Variations:; various reaction time;

5,7-Dihydroxy-3-(4-hydroxy-phenyl)-chromen-4-on (446-72-0) → orobol (480-23-9)

Conditions	Yield
With NADPH; cytochrome P450 In water at 37℃; pH=7.4; Enzyme kinetics; Further Variations:; Reagents;
With ascorbic acid In dimethyl sulfoxide at 50℃; for 1.5h; pH=9; Enzymatic reaction;

7,3',4'-trihydroxy-5-O-β-D-(2''-O-acetyl)xylopyranosyl-isoflavone → orobol (480-23-9)

Conditions	Yield
With hydrogenchloride for 2h; Heating;	3 mg

Acetic acid 3,5-bis-benzyloxy-2-[(E)-3-(3,4-bis-benzyloxy-phenyl)-acryloyl]-phenyl ester → orobol (480-23-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: thallium nitrate / CHCl3 / Ambient temperature 2: H2, triethylamine / 10percent Pd/C / ethyl acetate / 760 Torr / Ambient temperature 3: 5percent HCl / methanol / 2 h / Heating View Scheme

Acetic acid 3,5-bis-benzyloxy-2-[2-(3,4-bis-benzyloxy-phenyl)-3,3-dimethoxy-propionyl]-phenyl ester → orobol (480-23-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2, triethylamine / 10percent Pd/C / ethyl acetate / 760 Torr / Ambient temperature 2: 5percent HCl / methanol / 2 h / Heating View Scheme

eriodictyol (552-58-9) → orobol (480-23-9)

Conditions	Yield
With NADPH disodium salt; D-Galactose In dimethyl sulfoxide at 30℃; for 72h; Microbiological reaction;

3,5-dimethoxyphenol (500-99-2) → orobol (480-23-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate / 4 h / 75 °C 2: boron trifluoride diethyl etherate; methanesulfonyl chloride / 2 h / 100 °C 3: boron tribromide / dichloromethane / 18 h / 60 °C View Scheme

3,4-dihydroxyphenylacetate (102-32-9) → orobol (480-23-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate / 4 h / 75 °C 2: boron trifluoride diethyl etherate; methanesulfonyl chloride / 2 h / 100 °C 3: boron tribromide / dichloromethane / 18 h / 60 °C View Scheme

C27H30O15 → orobol (480-23-9)

Conditions	Yield
With hydrogenchloride In water at 90℃; for 2h; Reflux;

5,7-dihydroxy-chromen-4-one (31721-94-5) → orobol (480-23-9)

Conditions

Yield

Multi-step reaction with 4 steps 1: dmap; triethylamine / dichloromethane / 20 °C / Inert atmosphere 2: N-Bromosuccinimide; potassium acetate; acetic acid / 20 °C / Inert atmosphere 3: palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium carbonate / N,N-dimethyl-formamide; water / 90 °C / Inert atmosphere 4: pyridine hydrochloride / 150 °C / Inert atmosphere View Scheme

4-oxo-4H-chromene-5,7-diyl diacetate → orobol (480-23-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-Bromosuccinimide; potassium acetate; acetic acid / 20 °C / Inert atmosphere 2: palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium carbonate / N,N-dimethyl-formamide; water / 90 °C / Inert atmosphere 3: pyridine hydrochloride / 150 °C / Inert atmosphere View Scheme

3-bromo-4-oxo-4H-chromene-5,7-diyl diacetate → orobol (480-23-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium carbonate / N,N-dimethyl-formamide; water / 90 °C / Inert atmosphere 2: pyridine hydrochloride / 150 °C / Inert atmosphere View Scheme

orobol (480-23-9) + recombinant Escherichia coli expressing Streptomyces peucetius O-methyltransferase → 3',5,7-trihydroxy-4'-methoxyisoflavone (2284-31-3) + 3'-O-methylorobol (36190-95-1)

Conditions	Yield
With (R,S)-S-adenosyl-L-methionine In dimethyl sulfoxide at 40℃; for 24h; Enzymatic reaction;	A 33.3 mg B 27.9 mg

Upstream product

• 118949-94-3 6,8-di-C-β-D-glucopyranosyl-3',4',5,7-tetrahydroxyisoflavone 
• 20486-33-3 3',4',5,7-tetrahydroxyisoflavone β-D-glucopyranoside 
• 4419-11-8 2,2'-azobis-(2,4-dimethylvaleronitrile) 
• 446-72-0 5,7-Dihydroxy-3-(4-hydroxy-phenyl)-chromen-4-on 
• 500-99-2 3,5-dimethoxyphenol 
• 102-32-9 3,4-dihydroxyphenylacetate 
• 53084-11-0 3-(3,4-dimethoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one 
• 31721-94-5 5,7-dihydroxy-chromen-4-one 
• 552-58-9 eriodictyol 
• 66026-81-1 8-C-β-D-glucopyranosylorobol 
• 40316-84-5 3-(3,4-dimethoxyphenyl)-5,7-dimethoxychromen-4-one 

Downstream Products

• 2284-31-3 3',5,7-trihydroxy-4'-methoxyisoflavone 
• 36190-95-1 3'-O-methylorobol 

Relevant academic research and scientific papers

Reactions of genistein with alkylperoxyl radicals

Antioxidant actions of the soy isoflavone genistein are believed to contribute to its overall chemopreventive activity. However, the mechanisms of its antioxidant reactions remain unknown. The objective of this study was to characterize the reaction products of genistein (5,7,4'- trihydroxyisoflavone) with peroxyl radicals generated by thermolysis of 2,2'- azobis(2,4-dimethylvaleronitrile) (AMVN). Genistein oxidations with AMVN- derived peroxyl radicals yielded orobol (5,7,3',4'-tetrahydroxyisoflavone), a hydroxylated derivative of genistein, and several stable adducts of 4'- oxogenistein with AMVN-derived radicals. Some of these adducts include novel structures resulting from secondary oxidations of the AMVN-derived moiety. For all the observed oxidation products, the modifications occurred on the B- ring of the molecule. Genistein oxidation product structures provide potentially useful markers of genistein antioxidant chemistry.

Orobol: An Isoflavone Exhibiting Regulatory Multifunctionality against Four Pathological Features of Alzheimer's Disease

We report orobol as a multifunctional isoflavone with the ability to (i) modulate the aggregation pathways of both metal-free and metal-bound amyloid-β, (ii) interact with metal ions, (iii) scavenge free radicals, and (iv) inhibit the activity of acetylcholinesterase. Such a framework with multifunctionality could be useful for developing chemical reagents to advance our understanding of multifaceted pathologies of neurodegenerative disorders, including Alzheimer's disease.

Metabolism of genistein by rat and human cytochrome P450s

The metabolism of genistein (4',5,7-trihydroxyisoflavone), a phytoestrogen derived from soy products, was investigated using rat and human liver microsomes and recombinant human cytochrome P450 enzymes. Metabolism of genistein by microsomes obtained from rats treated with pyridine, phenobarbital, β-naphthoflavone, isosafrole, pregnenolone-16α-carbonitrile, or 3-methylcholanthrene resulted in very different product profiles consisting of five different NADPH- and time-dependent metabolites as observed by HPLC reverse-phase analysis at 260 nm. The metabolism of genistein was also investigated with recombinant human cytochrome P450 1A1, 1A2, 1B1, 2B6, 2C8, 2E1, or 3A4. P450s 1A1, 1A2, 1B1, and 2E1 metabolized genistein to form predominantly one product (peak 3) with smaller amounts of peaks 1 and 2. P450 3A4 produced two different products (peaks 4 and 5). Product peaks 1-3 eluted off the HPLC column prior to the parent compound genistein, and the UV/vis spectra, GC/MS, and ESI/MS/MS analyses support the conclusion that these products result from hydroxylation of genistein. The product peak 3 has been identified by tandem mass spectrometry as 3',4',5,7- tetrahydroxyisoflavone, also known as orobol, and peaks 1 and 2 appear to be hydroxylated at position 6 or 8.

Comparative phytochemical analysis of four Mexican Nymphaea species

Four Mexican Nymphaea species, N. ampla, N. pulchella, N. gracilis and N. elegans belonging to subgenera Brachyceras were analyzed. In this work two 5-glycosyl isoflavones, 7,3′,4′-trihydroxy-5-O-β-d-(2″- acetyl)-xylopyranosylisoflavone (1) and 7,3′,4′-trihydroxy-5-O- α-l-rhamnopyranosylisoflavone (2), were isolated from N. ampla and N. pulchella, respectively, together with other known 3-glycosyl flavones and triterpene saponins from the same four species. The structures were elucidated by 1D and 2D NMR, FABMS, and other spectroscopic analyses. These results confirmed that the four species were different from each other and established that N. pulchella represents a different taxa than N. ampla. In addition, the 5-glycosyl isoflavones could be considered as a taxonomic character of this group of plants.

Identification of ortho catechol-containing isoflavone as a privileged scaffold that directly prevents the aggregation of both amyloid β plaques and tau-mediated neurofibrillary tangles and its in vivo evaluation

In this study, polyhydroxyisoflavones that directly prevent the aggregation of both amyloid β (Aβ) and tau were expediently synthesized via divergent Pd(0)-catalyzed Suzuki-Miyaura coupling and then biologically evaluated. By preliminary structure–activity relationship studies using thioflavin T (ThT) assays, an ortho-catechol containing isoflavone scaffold was proven to be crucial for preventing both Aβ aggregation and tau-mediated neurofibrillary tangle formation. Additional TEM experiment confirmed that ortho-catechol containing isoflavone 4d significantly prevented the aggregation of both Aβ and tau. To investigate the mode of action (MOA) of 4d, which possesses an ortho-catechol moiety, 1H-15N HSQC NMR analysis was thoroughly performed and the result indicated that 4d could directly inhibit both the formation of Aβ42 fibrils and the formation of tau-derived neurofibrils, probably through the catechol-mediated nucleation of tau. Finally, 4d was demonstrated to alleviate cognitive impairment and pathologies related to Alzheimer's disease in a 5XFAD transgenic mouse model.

Phenolic constituents from the twigs of Betula schmidtii collected in Goesan, Korea

Six undescribed phenolic derivatives along with thirty two known compounds were isolated from the twigs of Betula schmidtii. The chemical structures were characterized through extensive spectroscopic analysis and chemical methods. All known compounds were first isolated in this plant. The anti-inflammatory effect of the isolates was tested by measuring nitric oxide production in lipopolysaccharide-activated BV-2 cells. Isotachioside, 4-allyl-2-hydrophenyl 1-O-β-D-apiosyl-(1 → 6)-β-D-glucopyranoside, genistein 5-O-β-D-glucoside, and prunetinoside showed a slight potency to lower the NO production against LPS-activated microglia with IC50 values of 23.9, 25.3, 28.8, and 34.0 μM, respectively.

Production and anti-melanoma activity of methoxyisoflavones from the biotransformation of genistein by two recombinant Escherichia coli strains

Biotransformation of the soy isoflavone genistein by sequential 3′-hydroxylation using recombinant Escherichia coli expressing tyrosinase from Bacillus megaterium and then methylation using another recombinant E. coli expressing O-methyltransferase from S

CATECHOL DERIVATIVES PREPARED BY USING TYROSINASE, METHOD FOR PREPARATION THEREOF, AND APPLICATION THEREOF

The present invention refers to using tyrosinase and pyrocatechole type structural material technology and exclusively on the basis of the response in the biosynthesis of, melanocyte secondary oxidation reaction by effectively inhibiting, mono phenol type primary structural material optionally catalyst only complex induced a are defined.. The present invention refers to using the same variety of functional pyrocatechole type materials, with high productivity and. there is provided a technique for production yield. (by machine translation)

A Versatile Microbial System for Biosynthesis of Novel Polyphenols with Altered Estrogen Receptor Binding Activity

Isoflavonoids possess enormous potential for human health with potential impact on heart disease and cancer, and some display striking affinities for steroid receptors. Synthesized primarily by legumes, isoflavonoids are present in low and variable abundance within complex mixtures, complicating efforts to assess their clinical potential. To satisfy the need for controlled, efficient, and flexible biosynthesis of isoflavonoids, a three-enzyme system has been constructed in yeast that can convert natural and synthetic flavanones into their corresponding isoflavones in practical quantities. Based on the determination of the substrate requirements of isoflavone synthase, a series of natural and nonnatural isoflavones were prepared and their binding affinities for the human estrogen receptors (ERα and ERβ) were determined. Structure activity relationships are suggested based on changes to binding affinities related to small variations on the isoflavone structure.

Syntheses of Isoflavones and Isoflavone Glycosides, and Their Inhibitory Activity against Bovine Liver &β-Galactosidase

To clarify the relationship between the structure and inhibitory action toward β-D-galactosidase (EC 3.2.1.21) of isoflavones and isoflavone glycosides, a number of polyhydroxyisoflavones, and the α-L-rhamnosides and β-L-quinovosides of daidzein and genistein were synthesized.Among the polyhydroxyisoflavones, 2',3',4',7-tetrahydroxyisoflavone showed the strongest inhibitory activity (Ki = 26 * 10-6 M).Among the glycosides, all the L-rhamnosides were strong inhibitors, of which genistein 4',7-di-O-α-L-rhamnoside was the strongest (Ki = 4.44 * 10-6 M), while all the isoflavone β-L-quinovosides were considerably weak or possessed no inhibition.