- Structure–activity relationship of phytoestrogen analogs as ERα/β agonists with neuroprotective activities
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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.
- Cho, Hye Won,Gim, Hyo Jin,Li, Hua,Subedi, Lalita,Kim, Sun Yeou,Ryu, Jae-Ha,Jeon, Raok
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- Method for preparing equol
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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.
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- Synthetic method for equol
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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.
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- Synthesis, structure-activity relationship analysis and kinetics study of reductive derivatives of flavonoids as Helicobacter pylori urease inhibitors
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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.
- Xiao, Zhu-Ping,Peng, Zhi-Yun,Dong, Jing-Jun,He, Juan,Ouyang, Hui,Feng, Yu-Ting,Lu, Chun-Lei,Lin, Wan-Qiang,Wang, Jin-Xiang,Xiang, Yin-Ping,Zhu, Hai-Liang
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p. 685 - 695
(2013/07/25)
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- 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
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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.
- Tilley, Andrew J.,Zanatta, Shannon D.,Qin, Cheng Xue,Kim, In-Kyeom,Seok, Young-Mi,Stewart, Alastair,Woodman, Owen L.,Williams, Spencer J.
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p. 2353 - 2361
(2012/05/07)
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- Processes for Preparing Isoflavonoids using 7-benzyloxy-3-(4-methoxyphenyl)-2H-1-benzopyran as a Starting Material
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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.
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Page/Page column 7-8
(2010/12/29)
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- Biotransformation of daidzein to equol by crude enzyme from Asaccharobacter celatus AHU1763 required an anaerobic environment
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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.
- Thawornkuno, Charin,Tanaka, Michiko,Sone, Teruo,Asano, Kozo
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experimental part
p. 1435 - 1438
(2009/12/06)
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- Synthesis of haginin E, equol, daidzein, and formononetin from resorcinol via an isoflavene intermediate
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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.
- Li, Sie-Rong,Chen, Po-Yuan,Chen, Liang-Yeu,Lo, Yi-Fang,Tsai, Ian-Lih,Wang, Eng-Chi
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supporting information; experimental part
p. 2121 - 2123
(2009/07/26)
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- Simple and efficient synthesis of (±)-equol and related derivatives
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A simple and efficient synthesis of (±)-equol and related derivatives in good yields from inexpensive starting materials has been described. Georg Thieme Verlag Stuttgart.
- Gupta, Atul,Ray, Suprabhat
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experimental part
p. 3783 - 3786
(2009/06/17)
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- o-Quinone methide based approach to isoflavans: application to the total syntheses of equol, 3′-hydroxyequol and vestitol
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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.
- Gharpure, Santosh J.,Sathiyanarayanan,Jonnalagadda, Prasad
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p. 2974 - 2978
(2008/09/20)
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- Preparation of Flavonoid Compounds
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Disclosed is an improved method for preparing the isoflavonoid compound (+/?)-equol, the method comprising reducing an organic diester of the isoflavone daidzein under hydrogen-transfer conditions using palladium hydroxide catalyst.
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Page/Page column 4
(2008/06/13)
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- Production of isoflavone derivatives
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Methods for the hydrogenation of isoflavones are described which provide access to workable quantities of isoflavan-4-ols, isoflav-3-enes, and isoflavans. The isoflavone derivatives can be obtained in high purity and in near quantitative yields whilst employing pharmaceutically acceptable reagents and solvents.
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Page/Page column 14
(2008/06/13)
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- 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 beta
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Equol is a metabolite produced in vivo from the soy phytoestrogen daidzein by the action of gut microflora. It is known to be estrogenic, so human exposure to equol could have significant biological effects. Equol is a chiral molecule that can exist as the enantiomers R-equol and S-equol. To study the biological activity of racemic (±)-equol, as well as that of its pure enantiomers, we developed an efficient and convenient method to prepare (±)-equol from available isoflavanoid precursors. Furthermore, we optimized a method to separate the enantiomers of equol by chiral HPLC, and we studied for the first time, the activities of the enantiomers on the two estrogen receptors, ERα and ERβ. In binding assays, S-equol has a high binding affinity, preferential for ERβ (Ki[ERβ]=16 nM; β/α=13 fold), that is comparable to that of genistein (K i[ERβ]=6.7 nM; β/α=16), whereas R-equol binds more weakly and with a preference for ERα (Ki[ERα]=50 nM; β/α=0.29). All equol isomers have higher affinity for both ERs than does the biosynthetic precursor daidzein. The availability and the in vitro characterization of the equol enantiomers should enable their biological effects to be studied in detail.
- Muthyala, Rajeev S.,Ju, Young H.,Sheng, Shubin,Williams, Lee D.,Doerge, Daniel R.,Katzenellenbogen, Benita S.,Helferich, William G.,Katzenellenbogen, John A.
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p. 1559 - 1567
(2007/10/03)
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