75187-63-2

Basic information

• Product Name: 7,8-DIHYDROXY-3-(4-HYDROXY-PHENYL)-CHROMEN-4-ONE
• Synonyms: 7,8-DIHYDROXY-3-(4-HYDROXY-PHENYL)-CHROMEN-4-ONE;4',7,8-Trihydroxy isoflavone;7,8-DIHYDROXY-3-(4-HYDROXY-PHENYL)-CHROMEN-4-ONE 98%;7,8-dihydroxy-3-(4-hydroxyphenyl)-4h-chroMen-4-one;YN1
• CAS NO: 75187-63-2
• Molecular Formula: C₁₅H₁₀O₅
• Molecular Weight: 270.24
• Mol File: 75187-63-2.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 558.2 °C at 760 mmHg
• Flash Point: 218.1 °C
• Appearance: white to beige/
• Density: 1.548 g/cm³
• Vapor Pressure: 4.58E-13mmHg at 25°C
• Refractive Index: 1.732
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble10mg/mL, clear
• CAS DataBase Reference: 7,8-DIHYDROXY-3-(4-HYDROXY-PHENYL)-CHROMEN-4-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: 7,8-DIHYDROXY-3-(4-HYDROXY-PHENYL)-CHROMEN-4-ONE(75187-63-2)
• EPA Substance Registry System: 7,8-DIHYDROXY-3-(4-HYDROXY-PHENYL)-CHROMEN-4-ONE(75187-63-2)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 75187-63-2(Hazardous Substances Data)

Usage

Biochem/physiol Actions

YN1 is a potent inhibitor of PFKFB3 (6-Phosphfructo-2-kinase/fructose-2,6-bisphosphatase: IC50 = 670 nM). PFKFB3 is over expressed in many cancers, and catalyzes the production of fructose-2,6-bisphosphate, which can potentiate PFK1 activity, enhancing glycolysis in tumor cells. YN1 inhibits glycolysis and proliferation in HeLa cells.

InChI:InChI=1/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-15-10(13(11)18)5-6-12(17)14(15)19/h1-7,16-17,19H

Synthetic route

7‐hydroxy‐8,4′‐dimethoxyisoflavone (37816-20-9) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
With aluminum (III) chloride; dimethylsulfide In dichloromethane at 5 - 20℃; for 4h;	93%

4′,7,8-trimethoxyisoflavone (37816-21-0) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
With aluminum (III) chloride; dimethylsulfide In dichloromethane at 5 - 20℃; for 6h;	95%

2-(4-hydroxyphenyl)-1-(2,3,4-trihydroxyphenyl)ethanone (77316-95-1) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
With boron trifluoride diethyl etherate; methanesulfonyl chloride at 80℃; for 3h;	70%
Stage #1: 2-(4-hydroxyphenyl)-1-(2,3,4-trihydroxyphenyl)ethanone With boron trifluoride diethyl etherate In N,N-dimethyl-formamide at 50 - 60℃; Cooling with ice; Stage #2: N,N-dimethyl-formamide With methanesulfonyl chloride at 50 - 70℃;	65%
Stage #1: 2-(4-hydroxyphenyl)-1-(2,3,4-trihydroxyphenyl)ethanone; N,N-dimethyl-formamide at 50℃; for 0.166667h; Stage #2: With methanesulfonyl chloride In N,N-dimethyl-formamide at 80℃; for 0.5h;	57%

2-(4-hydroxyphenyl)-1-(2,3,4-trihydroxyphenyl)ethanone (77316-95-1) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
With methanesulfonyl chloride In N,N-dimethyl-formamide at 60 - 70℃; for 1h;	83%

4-hydroxyphenylacetate (156-38-7) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent / BF3*Et2O / 3 h / 80 - 85 °C 2: 70 percent / BF3*Et2O; CH3SO2Cl / 3 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / 3 h / 80 °C / Inert atmosphere 2: methanesulfonyl chloride / 10 - 55 °C View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / 2 h / 80 - 90 °C 2: boron trifluoride diethyl etherate; trichlorophosphate / 2 h / 50 - 60 °C View Scheme

2-hydroxyresorcinol (87-66-1) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent / BF3*Et2O / 3 h / 80 - 85 °C 2: 70 percent / BF3*Et2O; CH3SO2Cl / 3 h / 80 °C View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride; zinc(II) chloride / diethyl ether / 0 - 20 °C 2: hydrogenchloride; water / Reflux 3: boron trifluoride diethyl etherate; methanesulfonyl chloride / 2 h / 50 - 100 °C View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / 2 h / 80 - 90 °C 2: boron trifluoride diethyl etherate; trichlorophosphate / 2 h / 50 - 60 °C View Scheme

7-Hydroxy-3-(4-methoxy-phenyl)-chromen-4-on (485-72-3) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-Bromosuccinimide / N,N-dimethyl-formamide / 4 h / 0 °C 2: copper(I) bromide / N,N-dimethyl-formamide; methanol / 4.5 h / 20 - 120 °C / Darkness 3: aluminum (III) chloride; dimethylsulfide / dichloromethane / 4 h / 5 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetone / 12 h / 60 °C 2.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 2.5 h / 0 °C 3.1: copper(I) bromide / N,N-dimethyl-formamide; methanol / 1 h 3.2: 2 h / 120 °C 4.1: aluminum (III) chloride; dimethylsulfide / dichloromethane / 6 h / 5 - 20 °C View Scheme

4-hydroxyphenylacetate (156-38-7) + phloroglucinol derivative → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / BF3*Et2O / 1 h / 60 - 70 °C 2: 83 percent / methanesulphonyl chloride / dimethylformamide / 1 h / 60 - 70 °C View Scheme

2-hydroxyresorcinol (87-66-1) + (+-)-benzoin (1 mol) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / BF3*Et2O / 1 h / 60 - 70 °C 2: 83 percent / methanesulphonyl chloride / dimethylformamide / 1 h / 60 - 70 °C View Scheme

4-cyanomethylphenol (14191-95-8) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride; zinc(II) chloride / diethyl ether / 0 - 20 °C 2: hydrogenchloride; water / Reflux 3: boron trifluoride diethyl etherate; methanesulfonyl chloride / 2 h / 50 - 100 °C View Scheme

8-bromo-7-hydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(I) bromide / N,N-dimethyl-formamide; methanol / 4.5 h / 20 - 120 °C / Darkness 2: aluminum (III) chloride; dimethylsulfide / dichloromethane / 4 h / 5 - 20 °C View Scheme

daidzein (486-66-8) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetone / 12 h / 60 °C 2.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 2.5 h / 0 °C 3.1: copper(I) bromide / N,N-dimethyl-formamide; methanol / 1 h 3.2: 2 h / 120 °C 4.1: aluminum (III) chloride; dimethylsulfide / dichloromethane / 6 h / 5 - 20 °C View Scheme

7-methoxy-3-(4-methoxyphenyl)-4H-chromen-4-one (1157-39-7) → 8-hydroxydaidzein (75187-63-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 2.5 h / 0 °C 2.1: copper(I) bromide / N,N-dimethyl-formamide; methanol / 1 h 2.2: 2 h / 120 °C 3.1: aluminum (III) chloride; dimethylsulfide / dichloromethane / 6 h / 5 - 20 °C View Scheme

Upstream product

• 156-38-7 4-hydroxyphenylacetate 
• 37816-21-0 4′,7,8-trimethoxyisoflavone 
• 117375-28-7 8-bromo-4′,7-dimethoxyisoflavone 
• 1157-39-7 7-methoxy-3-(4-methoxyphenyl)-4H-chromen-4-one 
• 486-66-8 daidzein 
• 37816-20-9 7‐hydroxy‐8,4′‐dimethoxyisoflavone 
• 485-72-3 7-Hydroxy-3-(4-methoxy-phenyl)-chromen-4-on 
• 14191-95-8 4-cyanomethylphenol 
• 87-66-1 2-hydroxyresorcinol 
• 77316-95-1 2-(4-hydroxyphenyl)-1-(2,3,4-trihydroxyphenyl)ethanone 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 116719-38-1 8-Hydroxy-Equol 
• 100001-87-4 4',7,8-triacetoxyisoflavone 
• 602329-55-5 4',8-dihexanoyloxyisoflavone 7-O-2'',3'',4'',6''-tetra-O-benzoyl-β-D-glucopyranoside 
• 602329-46-4 7,8-dihexanoyloxyisoflavone 4'-O-2'',3'',5''-tri-O-benzoyl-D-arabinofuranoside 
• 602329-57-7 4',8-dihexanoyloxyisoflavone 7-O-2'',3'',4''-tri-O-acetyl-α-L-rhamnopyranoside 
• 602329-48-6 4',8-dihexanoyloxyisoflavone 
• 602329-43-1 4',7,8-trihexanoyloxyisoflavone 
• 602329-47-5 7,8-dihexanoyloxy-4'-hydroxyisoflavone 
• 229612-58-2 4',8-diallyloxy-7-hydroxyisoflavone 
• 1443134-16-4 4',7,8-trihydroxy-2-isoflavene 

Relevant articles and documents

Synthesis and biological studies of 4′, 7, 8-trihydroxy-isoflavone metal complexes

A new series of complexes of a ligand 4′, 7, 8-trihydroxy-isoflavone with transition metal (zinc, copper, manganese, nickel, cobalt) and selenium have been synthesized and characterized with the aid of elemental analysis, IR, electron ionization mass spectrum (EI-MS) and 1H NMR spectrometric techniques. The compounds were evaluated for their in vitro antibacterial activities and antitumor properties. The metal complexes were found to be more active than the free ligand. Investigation on the interaction between the complexes and calf-thymus DNA (CT DNA) showed that the absorbance of CT DNA increased and the maximum peak (λmax = 260 nm) red-shifted, while the intensity of fluorescence spectra of Epstein-Bart DNA (EB-DNA) gradually weakened, which indicated that all of these metal complexes tightly combined with CT DNA.

Synthetic method of polyhydroxy isoflavone

The invention discloses a synthetic method of polyhydroxy isoflavone. The method comprises the following steps: (1) reacting 4', 7-dimethoxyisoflavone with N-bromosuccinimide, and controlling the molar ratio of 4', 7-dimethoxyisoflavone to N-bromosuccinimide and a reaction temperature to enable one or two hydrogen atoms on a 4', 7-dimethoxyisoflavone carbon ring to be substituted by bromine atomsto generate corresponding bromide; (2), enabling the bromide in the (2) to react with sodium methoxide under the action of cuprous salt to enable bromine atoms on a carbon ring of the bromide to be substituted by methoxy to obtain a methoxylation product; and (3), carrying out a demethylation reaction on the methoxylation product obtained in the (3) under the action of aluminum chloride and dimethyl sulfide to obtain polyhydroxy isoflavone. The method has the advantages of abundant sources of initial raw materials, mild reaction conditions, good selectivity and high yield, and is suitable forindustrial production. The purity of the product is greater than 99.0%, and the product can be used for pharmacological activity research.

Enzymatic studies of isoflavonoids as selective and potent inhibitors of human leukocyte 5-lipo-oxygenase

Continuing our search to find more potent and selective 5-LOX inhibitors, we present now the enzymatic evaluation of seventeen isoflavones (IR) and nine isoflavans (HIR), and their in vitro and in cellulo potency against human leukocyte 5-LOX. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5-LOX (IR-2, HIR-303, and HIR-309), with IC50 values at least 10 times lower than those of 12-LOX, 15-LOX-1, and 15-LOX-2. Of these three, IR-2 (6,7-dihydroxy-4-methoxy-isoflavone, known as texasin) was the most selective 5-LOX inhibitor, with over 80-fold potency difference compared with other isozymes; Steered Molecular Dynamics (SMD) studies supported these findings. The presence of the catechol group on ring A (6,7-dihydroxy versus 7,8-dihydroxy) correlated with their biological activity, but the reduction of ring C, converting the isoflavones to isoflavans, and the substituent positions on ring B did not affect their potency against 5-LOX. Two of the most potent/selective inhibitors (HIR-303 and HIR-309) were reductive inhibitors and were potent against 5-LOX in human whole blood, indicating that isoflavans can be potent and selective inhibitors against human leukocyte 5-LOX in vitro and in cellulo. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5-LOX (IR-2, HIR-303, and HIR-309), with IC50 values at least 10 times lower than those of 12-LOX, 15-LOX-1, and 15-LOX-2. Docking and steered molecular dynamics were performed to determinate the structure-activity relationship.