94105-90-5

Basic information

• Product Name: (+/-)-EQUOL
• Synonyms: 7,4'-HoMoisoflavane;NV 07α;3-(4-Hydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-7-ol 7-Hydroxy-3-(4-hydroxyphenyl)chroman 4',7-Isoflavandiol;3,4-Dihydro-3-(4-hydroxyphenyl)-2H-chromen-7-ol, (+/-)-Equol, 4',7-Isoflavandiol, 7-Hydroxy-3-(4-hydroxyphenyl)chroman;4',7-Isoflavandiol, (+/-)-Equol;4′,7-Dihydroxyisoflavane;(+/-)-Equol (GMP);(±)-EQUOL >= 99.0% (TLC)
• CAS NO: 94105-90-5
• Molecular Formula: C₁₅H₁₄O₃
• Molecular Weight: 242.28
• EINECS: 1312995-182-4
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;metabolite;Metabolites
• Mol File: 94105-90-5.mol

Chemical Properties

• Melting Point: 158-160?C
• Boiling Point: 441.7 °C at 760 mmHg
• Flash Point: 220.9 °C
• Appearance: solid
• Density: 1.286 g/cm³
• Vapor Pressure: 2.05E-08mmHg at 25°C
• Refractive Index: 1.644
• Storage Temp.: -20°C Freezer
• Solubility: soluble in Ethanol
• PKA: 9.94±0.40(Predicted)
• Water Solubility: Soluble in DMSO and methanol or 100% ethanol. Insoluble in water.
• Sensitive: Hygroscopic
• BRN: 87752
• CAS DataBase Reference: (+/-)-EQUOL(CAS DataBase Reference)
• NIST Chemistry Reference: (+/-)-EQUOL(94105-90-5)
• EPA Substance Registry System: (+/-)-EQUOL(94105-90-5)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 94105-90-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(+/-)-EQUOL is used as a weak estrogenic agonist and competitive inhibitor of 17β-estradiol at the estradiol receptor. Its ability to modulate estrogen receptor activity makes it a potential candidate for the development of drugs targeting hormone-related conditions and diseases.
Used in Cancer Research:
(+/-)-EQUOL is used as an inducer of breast cancer cell proliferation in vitro at concentrations as low as 100 nM. Its effects on cell transformation and signaling pathways, such as the MEK/ERK/p90RSK/activator protein-1 pathway, make it a valuable tool for studying the mechanisms of cancer development and progression.
Used in Hormone Regulation:
(+/-)-EQUOL functions as a DHT blocker, which can be useful in the development of treatments for hormone-related disorders, such as androgenetic alopecia and prostate enlargement.
Used in Nutraceutical Industry:
As a human urinary metabolite of the soy isoflavones daidzein, (+/-)-EQUOL can be utilized in the development of nutraceutical products that target hormone balance and promote overall health.

Biological Activity

Metabolite of daidzein. Weak estrogenic agonist, and competitive inhibitor of 17β-estradiol at the estradiol receptor.(R,S)-Equol is a flavonoid. Racemic mixture. This is a metabolite that is produced in vivo from soy phytoestrogen daidzein from gut microflora. (R,S)-Equol inhibits 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced neoplastic cell transformation by targeting the MEK/ERK/p90RSK/activator protein-1 signalling pathway. (R,S)-Equol shows positive effects on the incidence of prostate cancer. Functions as a DHT blocker. Preferentially activates estrogen receptor β (ERβ).

Biochem/physiol Actions

Metabolite of daidzein. Weak estrogenic agonist, and competitive inhibitor of 17β-estradiol at the estradiol receptor.

References

Equol, a natural estrogenic metabolite from soy isoflavones convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and betaR. S. Muthyala, Y. H. Ju, S. Sheng, L. D. Williams, D. R. Doerge, B. S. Katzenellenbogen, W. G. Helferich, J. A. Katzenellenbogen, Bioorg. Med. Chem. 2004, 12, 1559.Isolation and identification of new bacterial stains producing equol from Pueraria lobate extract fermentationJ. E. Kwon, J. Lim, I. Kim, D. Kim, S. C. Kang, PLoS ONE 2018, 13, e0192490.Setchell, K.D.R., Clerici, C., Lephart, E.D., et al. S-equol, a potent ligand for estrogen receptor β, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am. J. Clin. Nutr. 81(5), 1072-1079 (2005).Liu, H., Du, J., Hu, C., et al. Delayed activation of extracellular-signal-regulated kinase ? is involved in genistein- and equol-induced cell proliferation and estrogen-receptor-α-mediated transcription in MCF-7 breast cancer cells. Journal of Nutritional Biochemistry (2009).

InChI:InChI=1/C15H14O3/c16-13-4-1-10(2-5-13)12-7-11-3-6-14(17)8-15(11)18-9-12/h1-6,8,12,16-17H,7,9H2

Upstream product

• 486-66-8 daidzein 
• 10499-17-9 3,4-dihydro-7-hydroxy-3-(4-methoxyphenyl)-2H-1-benzopyran 
• 485-72-3 7-Hydroxy-3-(4-methoxy-phenyl)-chromen-4-on 
• 13401-41-7 7-acetoxy-3-(4-acetoxy-phenyl)-chroman 
• 3682-01-7 daidzein diacetate 
• 1029608-32-9 C₂₉H₂₆O₃ 
• 1118431-82-5 3-(4-ethoxyphenyl)-7-methoxychroman 
• 17238-05-0 dihydrodaidzein 
• 1370331-08-0 4',7-dibenzyloxy-2-morpholinoisoflav-3-ene 
• 40167-10-0 2-[4-(benzyloxy)phenyl]acetaldehyde 
• 61439-59-6 2-(4-benzyloxyphenyl)ethanol 
• 81267-65-4 idronoxil 
• 108-46-3 recorcinol 
• 156-38-7 4-hydroxyphenylacetate 

Downstream Products

• 4366-35-2 4',7-dimethoxyisoflavan 
• 13401-41-7 7-acetoxy-3-(4-acetoxy-phenyl)-chroman 
• 104411-14-5 <6,8,3',5'-2H4>equol 
• 221054-79-1 (+)-Equol 
• 531-95-3 equol 

Relevant articles and documents

Structure–activity relationship of phytoestrogen analogs as ERα/β agonists with neuroprotective activities

A set of isoflavononid and flavonoid analogs was prepared and evaluated for estrogen receptor α (ERα) and ERβ transactivation and anti-neuroinflammatory activities. Structure–activity relationship (SAR) study of naturally occurring phytoestrogens, their metabolites, and related isoflavone analogs revealed the importance of the C-ring of isoflavonoids for ER activity and selectivity. Docking study suggested putative binding modes of daidzein 2 and dehydroequol 8 in the active site of ERα and ERβ, and provided an understanding of the promising activity and selectivity of dehydroequol 8. Among the tested compounds, equol 7 and dehydroequol 8 were the most potent ERα/β agonists with ERβ selectivity and neuroprotective activity. This study provides knowledge on the SAR of isoflavonoids for further development of potent and selective ER agonists with neuroprotective potential.

Method for preparing equol

The invention relates to a method for preparing equol. The method comprises the following steps: S1, synthesizing benzohydropyran: namely weighing daidzein raw materials, dissolving the daidzein raw materials in dimethyl formamide (DMF), adding palladium carbon into a hydrogenation kettle, carrying out reacting at a same speed under constant temperature and constant pressure, filtering out the catalyst, adding ice water into the filtrate, carrying out stirring to separate out white solid, and carrying out filtering, water washing and drying to obtain an intermediate a; S2, synthesizing a condensate: namely adding the intermediate a, dichloroethane and polyphosphoric acid into a three-mouth bottle, carrying out a reflux reaction, carrying out cooling, adding the obtained substance into icewater, taking an organic phase by layering, carrying out drying with sodium sulfate, concentrating dichloroethane to obtain a yellow oily substance, and carrying out recrystallizing with 90% ethanol water to obtain an intermediate b; and S3, synthesizing equol: namely adding the intermediate b, DMF and a catalyst into a hydrogenation kettle, filtering out the catalyst after a reaction at constanttemperature and constant pressure, adding the filtrate into ice water, carrying out stirring to separate out a gray solid, carrying out filtering, and recrystallizing the filter cake with 70% methanolwater to obtain the equol. The method has the advantages of simple steps, high total yield, environmental protection and easy operation.

Synthetic method for equol

The invention provides a synthetic method for equol. The synthetic method comprises the following steps: with daidzein as a raw material, subjecting daidzein to an esterification reaction to obtain a compound B; subjecting the compound B to olefinic-bond conjugation and a reduction reaction of a carbonyl group so as to obtain a compound C; subjecting the compound C to a dehydration reaction so as to obtain a compound D; and carrying out double-bond hydrogenation on the compound D so as to obtain equol. The synthetic method provided by the invention has the advantages of short synthesis steps, simple operation, economic performance, environmental protection, yield of 70% or above in each step, obviously increased overall yield and suitability for industrial mass production.

Synthesis, structure-activity relationship analysis and kinetics study of reductive derivatives of flavonoids as Helicobacter pylori urease inhibitors

In a continuing study for discovering urease inhibitors based on flavonoids, nineteen reductive derivatives of flavonoids were synthesized and evaluated against Helicobacter pylori urease. Analysis of structure-activity relationship disclosed that 4-deoxy analogues are more potent than other reductive products. Out of them, 4′,7,8-trihydroxyl-2-isoflavene (13) was found to be the most active with IC50 of 0.85 μM, being over 20-fold more potent than the commercial available urease inhibitor, acetohydroxamic acid (AHA). Kinetics study revealed that 13 is a competitive inhibitor of H. pylori urease with a Ki value of 0.641 μM, which is well matched with the results of molecular docking. Biological evaluation and mechanism study of 13 suggest that it is a good candidate for discovering novel anti-gastritis and anti-gastric ulcer agent.

2-Morpholinoisoflav-3-enes as flexible intermediates in the synthesis of phenoxodiol, isophenoxodiol, equol and analogues: Vasorelaxant properties, estrogen receptor binding and Rho/RhoA kinase pathway inhibition

Isoflavone consumption correlates with reduced rates of cardiovascular disease. Epidemiological studies and clinical data provide evidence that isoflavone metabolites, such as the isoflavan equol, contribute to these beneficial effects. In this study we developed a new route to isoflavans and isoflavenes via 2-morpholinoisoflavenes derived from a condensation reaction of phenylacetaldehydes, salicylaldehydes and morpholine. We report the synthesis of the isoflavans equol and deoxygenated analogues, and the isoflavenes 7,4′-dihydroxyisoflav-3-ene (phenoxodiol, haganin E) and 7,4′-dihydroxyisoflav-2-ene (isophenoxodiol). Vascular pharmacology studies reveal that all oxygenated isoflavans and isoflavenes can attenuate phenylephrine-induced vasoconstriction, which was unaffected by the estrogen receptor antagonist ICI 182,780. Furthermore, the compounds inhibited U46619 (a thromboxane A2 analogue) induced vasoconstriction in endothelium-denuded rat aortae, and reduced the formation of GTP RhoA, with the effects being greatest for equol and phenoxodiol. Ligand displacement studies of rat uterine cytosol estrogen receptor revealed the compounds to be generally weak binders. These data are consistent with the vasorelaxation activity of equol and phenoxodiol deriving at least in part by inhibition of the RhoA/Rho-kinase pathway, and along with the limited estrogen receptor affinity supports a role for equol and phenoxodiol as useful agents for maintaining cardiovascular function with limited estrogenic effects.

Processes for Preparing Isoflavonoids using 7-benzyloxy-3-(4-methoxyphenyl)-2H-1-benzopyran as a Starting Material

Disclosed herein are processes for the preparation of isoflavonoids, in particular haginin E, equol, daidzein, formononetin and the like, in which 7-benzyloxy-3-(4-methoxyphenyl)-2H-1-benzopyran is used as a common starting material.

Biotransformation of daidzein to equol by crude enzyme from Asaccharobacter celatus AHU1763 required an anaerobic environment

Asaccharobacter celatus AHU1763 is a Gram-positive, obligate anaerobic, non-spore forming, rod-shaped bacteria that was successfully isolated from rat cecal content. Daizein was converted to equol via dihydrodaidzein by this bacterium. A crude enzyme that converted daidzein to dihydrodaidzein was detected mainly in the culture supernatant. The ability of this enzyme dropped after the culture supernatant was exposed to a normal atmospheric environment for even 5 min. Furthermore, the enzyme responsible for changing dihydrodaidzein to equol was detected mainly in the cell debris, which required anaerobic conditions for its activity.

Synthesis of haginin E, equol, daidzein, and formononetin from resorcinol via an isoflavene intermediate

New syntheses of haginin E, equol, daidzein, and formononetin are described in this Letter. Through a sequence of a Wittig reaction, O-alkylation, and another Wittig reaction, 4-benzyloxysalicylaldehyde, which was prepared from resorcinol in two steps, was converted into the desired diene in one pot. Subsequently, the prepared diene was subjected to ring-closing metathesis using Grubbs' catalyst (II) to construct the desired isoflavene intermediate. Using the prepared isoflavene, certain isoflavonoids such as haginin E, equol, daidzein, formononetin, and other related compounds were derived smoothly and in good overall yields.

Simple and efficient synthesis of (±)-equol and related derivatives

A simple and efficient synthesis of (±)-equol and related derivatives in good yields from inexpensive starting materials has been described. Georg Thieme Verlag Stuttgart.

o-Quinone methide based approach to isoflavans: application to the total syntheses of equol, 3′-hydroxyequol and vestitol

A concise strategy is developed for the synthesis of isoflavans employing a Diels-Alder reaction between o-quinone methides and aryl-substituted enol ethers followed by reductive cleavage of the acetal group. The method is extended towards the total syntheses of equol, 3′-hydroxyequol and vestitol.