- 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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- Total synthesis of eryvarin H and its derivatives and their biological activity as ERRγ inverse agonist
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Total synthesis of eryvarin H and a biological investigation of its analogues as a potential inverse agonist of ERRγ are described here. Among the 13 analogues prepared by the modular synthetic route, eryvarin H and compound 12 showed meaningful ERRγ inverse agonistic activities along with moderate selectivity over ERα and other nuclear receptors in the cell-based reporter gene assay.
- Koo, Ja Young,Oh, Sangmi,Cho, Seung-Rye,Koh, Minseob,Oh, Won-Keun,Choi, Hueng-Sik,Park, Seung Bum
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p. 5782 - 5786
(2013/09/12)
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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 6-7
(2010/12/29)
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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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- Synthesis of various kinds of isoflavones, isoflavanes, and biphenyl- ketones and their 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities
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Forty-eight kinds of isoflavones (8), thirty-one isoflavanes (9), and forty-seven biphenyl-ketones (10, 10') were synthesized from eleven kinds of substituted phenols (11) and six phenylacetic acids (12). Among them, seventy-five compounds are new. The radical scavenging activities of these compounds were evaluated using 1,1- diphenyl-2-picrylhydrazyl (DPPH) at pH 6.0. We found that thirty-nine out of forty-three compounds having a catechol moiety on either the A- or the B-ring exhibited a high activity (ED50=12-54 μM) similar to that of catechin. In these cases, the remaining part of their structure seemed to have little effect on their activity. Many 6- or 8-hydroxyisoflavanes (9E-I) and their biphenyl-ketone derivatives (10E-H) also showed a high activity (ED50=50=26-32 μM). This study suggests that natural isoflavones have the possibilities of exhibiting antioxidant activities through the hydroxylation at the C6-, C8-, or C3'-position or the formation of the isoflavanes (9) and/or the biphenyl-ketone derivatives (10') by metabolism or biotransformation.
- Goto, Hideyuki,Terao, Yoshiyasu,Akai, Shuji
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scheme or table
p. 346 - 360
(2009/12/27)
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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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- Method for enantioselective hydrogenation of chromenes
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A method for preparing an enantiomeric chromane, by asymmetrically hydrogenating a chromene compound in the presence of an Ir catalyst having a chiral ligand. The method includes the enantioselective preparation of enantiomeric equol. A preferred Ir catalyst has a chiral phosphineoxazoline ligand. Enantiomeric chromanes of high stereoselective purity can be obtained.
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Page/Page column 12
(2008/06/13)
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- ISOFLAVENE SYNTHETIC METHOD AND CATALYST
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An improved process for the synthesis of hydroxy-substituted isoflavan-4-ol and isoflavene compounds from isoflavones is described. The invention further relates to a novel basified hydrogenation catalyst and uses thereof.
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Page/Page column 16-17
(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 11
(2008/06/13)
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- Therapeutic methods and compositions involving isoflavones
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Therapeutic methods of treatment, compositions and foodstuffs are described which contain isoflavone compounds described by general formula (1), in which Z is H, R1 is H, or RACO where RA is C1-10alkyl or an amino acid, R2 is H, OH, or ORB where RB is an amino acid, or CORA where RA is as previously defined, W is H, A is H or OH, and B is selected from (a), (b), (c), or W is H, and A and B taken together form a six-membered ring selected from (d), or W, A and B taken with the groups with which they are associated comprise (e), or W and A taken together with the groups with which they are associated comprise (f) and B is (g) wherein R3 is H, CORA where RA is as previously defined, CO2Rc where RC is C1-10alkyl, or CORB where RB is as previously defined, R4 is H, CORD where RD is H, OH, C1-10alkyl or an amino acid, CO2RC where RC is as previously defined, CORE where RE is H, C1-10alkyl or an amino acid, COOH, CORC where RC is as previously defined, or CONHRE where RE is as previously defined, R5 is H, CORC where RC is as previously defined, or CORCORE where RC and RE are as previously defined, and where the two R5 groups are attached to the same group they are the same or different, R6 is H or hydroxy C1-10alkyl, X is preferably O, but may be N or S, and Y is (h) where R7 is H, or C1-10alkyl.
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- A Synthesis of Hydroxylated Isoflavylium Salts and Their Reduction Products
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Phloroglucinol reacts with arylmalondialdehydes in the presence of hydrochloric acid to form 5,7-dihydroxyisoflavylium salts.Reduction of these salts can be utilized to form isoflav-2-enes, isoflav-3-enes or isoflavans.
- Liepa, Andris J.
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p. 2647 - 2655
(2007/10/02)
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