- 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.
- Cho, Hye Won,Gim, Hyo Jin,Li, Hua,Subedi, Lalita,Kim, Sun Yeou,Ryu, Jae-Ha,Jeon, Raok
-
-
- A Concise Enantiodivergent Synthesis of Equol
-
Equol, a nonsteroidal estrogen produced from the metabolism of the isoflavonoid phytoestrogen daidzein, has been synthesized as both enantioenriched forms based on MacMillan's α-Arylation of carbonyl compound mediated by amino acid derived indazolidinones and copper precatalysts. The natural form of (S)-equol and its enantiomer (R)-equol have been synthesized in 8 steps from 2,4-dimethoxybenzaldehyde with good enantiomeric purity (90% ee and 90% ee, respectively).
- Uemura, Takahito,Saito, Yusuke,Sonoda, Motohiro,Tanimori, Shinji
-
p. 693 - 696
(2020/12/23)
-
- 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.
- -
-
-
- Rhodium-catalyzed asymmetric addition of arylboronic acids to 2: H-chromenes leading to 3-arylchromane derivatives
-
Asymmetric addition of arylboronic acids to 2H-chromenes proceeded in the presence of a hydroxorhodium/chiral diene catalyst to give 3-arylchromanes in high yields with high enantioselectivity. The reaction involves 1,4-Rh shift before protonation to release the addition product and to regenerate the hydroxorhodium species.
- Umeda, Moeko,Sakamoto, Kana,Nagai, Tomotaka,Nagamoto, Midori,Ebe, Yusuke,Nishimura, Takahiro
-
supporting information
p. 11876 - 11879
(2019/10/11)
-
- A general asymmetric route to enantio-enriched isoflavanes via an organocatalytic annulation of o-quinone methides and aldehydes
-
Reported herein is a general approach to optically active isoflavanes based on a chiral amine-catalyzed [4 + 2] asymmetric annulation of o-quinone methides and aldehydes. A number of naturally occurring isoflavanes, including equol, sativan, isosativan, v
- Zhang, Jian,Zhang, Shuangzhan,Yang, Huixin,Zhou, Ding,Yu, Xueting,Wang, Wei,Xie, Hexin
-
supporting information
p. 2407 - 2411
(2018/05/24)
-
- Enantioselective Total Synthesis of Natural Isoflavans: Asymmetric Transfer Hydrogenation/Deoxygenation of Isoflavanones with Dynamic Kinetic Resolution
-
A concise and highly enantioselective synthesis of structurally diverse isoflavans from a single chromone is described. The key transformation is a single-step conversion of racemic isoflavanones into virtually enantiopure isoflavans by domino asymmetric transfer hydrogenation/deoxygenation with dynamic kinetic resolution.
- Ke?berg, Anton,Lübken, Tilo,Metz, Peter
-
p. 3006 - 3009
(2018/05/28)
-
- A chiral pool approach for asymmetric syntheses of both antipodes of equol and sativan
-
For the first time, both antipodes of the isoflavans, equol and sativan were synthesized in >98% ee with good overall yields starting from readily available starting materials. The chiral isoflavan, (?)-equol is produced from soy isoflavones, formonentin and daidzein by the action of intestinal bacteria in certain groups of population and other chiral isoflavans are reported from various phytochemical sources. To produce these chiral isoflavans in gram quantities, Evans’ enantioselective aldol condensation was used as a chiral-inducing step to introduce the required chirality at the C-3 position. Addition of chiral boron-enolate to substituted benzaldehyde resulted in functionalized syn-aldol products with >90% yield and excellent diastereoselectivity. Functional group transformations followed by intramolecular Mitsunobu reaction and deprotection steps resulted the target compounds, S-(?)-equol and S-(+)-sativan, with high degree of enantiopurity. By simply switching the chiral auxiliary to (S)-4-benzyloxazolidin-2-one and following the same synthetic sequence the antipodes, R-(+)-equol and R-(?)-sativan were achieved. Both enantiomers are of interest from a clinical and pharmacological perspective and are currently being developed as nutraceutical and pharmacological agents. This flexible synthetic process lends itself quite readily to the enantioselective syntheses of other biologically active C-3 chiral isoflavans.
- Yalamanchili, Chinni,Chittiboyina, Amar G.,Chandra Kumar Rotte, Sateesh,Katzenellenbogen, John A.,Helferich, William G.,Khan, Ikhlas A.
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p. 2020 - 2029
(2018/03/21)
-
- Cellulose type chiral stationary phase based on reduced graphene oxide@silica gel for the enantiomer separation of chiral compounds
-
The graphene oxide (GO) was covalently coupled to the surfaces of silica gel (SiO2) microspheres by amide bond to get the graphene oxide@silica gel (GO@SiO2). Then, the GO@SiO2 was reduced with hydrazine to the reduced graphene oxide@silica gel (rGO@SiO2), and the cellulose derivatives were physically coated on the surfaces of rGO@SiO2 to prepare a chiral stationary phase (CSP) for high performance liquid chromatography. Under the optimum experimental conditions, eight benzene-enriched enantiomers were separated completely, and the resolution of trans-stilbene oxide perfectly reached 4.83. Compared with the blank column of non-bonded rGO, the separation performance is better on the new CSP, which is due to the existence of rGO to produce special retention interaction with analytes, such as π-π stacking, hydrophobic effect, π-π electron-donor–acceptor interaction, and hydrogen bonding. Therefore, the obtained CSP shows special selectivity for benzene-enriched enantiomers, improves separation selectivity and efficiency, and rGO plays a synergistic effect with cellulose derivatives on enantioseparation.
- Li, Yuanyuan,Li, Qiang,Zhu, Nan,Gao, Zhuxian,Ma, Yulong
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p. 996 - 1004
(2018/07/29)
-
- Iridium-Catalyzed Asymmetric Hydrogenation of 2H-Chromenes: A Highly Enantioselective Approach to Isoflavan Derivatives
-
A highly efficient (aS)-Ir/In-BiphPHOX-catalyzed asymmetric hydrogenation of substituted 2H-chromenes and substituted benzo[e][1,2]oxathiine 2,2-dioxides is described. A series of 2H-chromenes and benzo[e][1,2]oxathiine 2,2-dioxides were hydrogenated to give the target products in high yields (92-99%) with excellent enantioselectivities (up to 99.7% ee) using our catalytic system. This reaction provides a direct and efficient method for the construction of chiral benzo six-membered oxygen-containing compounds.
- Xia, Jingzhao,Nie, Yu,Yang, Guoqiang,Liu, Yangang,Zhang, Wanbin
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p. 4884 - 4887
(2017/09/23)
-
- 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.
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-
-
- ANHYDROUS CRYSTALLINE FORM OF S-EQUOL
-
An anhydrous crystalline form of S-equol has been discovered. Form I, the anhydrous crystalline form of S-equol has been isolated and characterized for the first time. As compared to other forms of S-equol, such as the known hydrate or other solvate forms, the anhydrous crystalline form of S-equol has improved properties.
- -
-
Paragraph 0039
(2016/05/10)
-
- PRODUCTION METHOD OF OPTICALLY ACTIVE 3-SUBSTITUTED CHROMAN-4-OL COMPOUND
-
PROBLEM TO BE SOLVED: To provide a versatile and highly productive production method of an optically active 3-substituted chroman-4-ol compound. SOLUTION: A production method of an optically active 3-substituted chroman-4-ol compound includes performing a reduction reaction of a 3-substituted chroman-4-one compound in the presence of a metal complex represented by formula (I) (in formula (I), M represents a group 8 transition metal or the like, each of R1 and R2 independently represents a hydrogen atom, a 1-6C alkyl group or the like, R3 represents a 1-6C alkyl group or the like, R4 represents a 1-6C alkyl group or the like, Ar represents benzene bonded with M via a π bond or the like, and X represents a carbonyloxy group or the like). COPYRIGHT: (C)2015,JPOandINPIT
- -
-
Paragraph 0079-0081
(2017/01/02)
-
- The flavan-isoflavan rearrangement: Bioinspired synthetic access to isoflavonoids via 1,2-shift-alkylation sequence
-
An approach to 2-substituted isoflavonoids is reported based on the 1,2-shift of the aryl group in the catechin skeleton followed by the in situ alkylation. Synthesis of (-)-equol, a natural isoflavan with estrogenic activities, was achieved.
- Nakamura, Kayo,Ohmori, Ken,Suzuki, Keisuke
-
supporting information
p. 7012 - 7014
(2015/04/22)
-
- PROCESS FOR PRODUCING (S)-EQUOL
-
The present application relates to an improved process for the preparation of (S)-equol (1). The present application also relates to novel intermediates of formula (7), (7A), (8) and (9) and their use for the synthesis of (5)-equol.
- -
-
-
- 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.
- 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
-
p. 685 - 695
(2013/07/25)
-
- IMPROVED PROCESS FOR PRODUCING (S)-EQUOL
-
The present application relates to an improved process for the preparation of (S)- equol (1). The present application also relates to novel intermediates of formula (7), (7A), (8) and (9) and their use for the synthesis of (S)-equol.
- -
-
Page/Page column 22; 23
(2013/10/21)
-
- Deracemization of α-aryl hydrocoumarins via catalytic asymmetric protonation of ketene dithioacetals
-
An unprecedented catalytic asymmetric protonation of ketene dithioacetals is described. Various racemic α-aryl hydrocoumarin derivatives are transformed into enantioenriched dithioacetal-protected hydrocoumarins in the presence of a chiral Br?nsted acid catalyst. A newly developed phosphoric acid, featuring the 3,5-bis(pentafluorothio)phenyl (3,5-(SF5) 2C6H3) substituent, is introduced. The obtained products can be easily converted into either hydrocoumarins or the corresponding chromans via simple hydrolysis or hydrogenation, respectively.
- Lee, Ji-Woong,List, Benjamin
-
p. 18245 - 18248
(2013/01/15)
-
- Enantioselective iridium-catalyzed hydrogenation of α-arylcinnamic acids and synthesis of (S)-equol
-
By using iridium catalyst based on chiral spiro phosphine-oxazoline ligands, the hydrogenation of α-arylcinnamic acids was accomplished under ambient pressure and low catalyst loading (as low as 0.01 mol %), providing useful 2,3-diarylpropionic acids in high yields with excellent enantioselectivities (up to 99% ee). A catalytic enantioselective synthesis of (S)-equol with the present hydrogenation reaction as a key step was accomplished starting from commercially available starting materials in six steps with 48.4% overall yield.
- Yang, Shuang,Zhu, Shou-Fei,Zhang, Can-Ming,Song, Song,Yu, Yan-Bo,Li, Shen,Zhou, Qi-Lin
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p. 5172 - 5178
(2012/07/31)
-
- 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.
- Tilley, Andrew J.,Zanatta, Shannon D.,Qin, Cheng Xue,Kim, In-Kyeom,Seok, Young-Mi,Stewart, Alastair,Woodman, Owen L.,Williams, Spencer J.
-
p. 2353 - 2361
(2012/05/07)
-
- Development of bioluminescent enzyme immunoassay for S-equol using firefly luciferase and its application to the assessment of equol-producer status
-
In this study, we developed a specific bioluminescent enzyme immunoassay (BLEIA) for S-equol, employing firefly luciferase as a labeling enzyme, as an alternative to HPLC methods. Satisfactory correlation (r=0.992) was shown when this S-equol BLEIA was compared with HPLC. The cross-reactivity with R-equol as its diastereoisomer is 10-transformed urinary S-equol to daidzein ratio threshold of -1.75, namely, 34% of men and 19% of women. When the changes in concentration of urinary equol and daidzein were measured after ingestion of isoflavone, the maximum concentration (C max) of urinary equol appeared after 9.6 h of isoflavone consumption; this Cmax was 2 h later than that for daidzein. The S-equol BLEIA documented in this study is expected to be an important tool for the assessment of equol producer status and demonstration of the bioavailability of isoflavone.
- Minekawa, Takayuki,Kambegawa, Akira,Shindome, Kumiko,Ohkuma, Hiroshi,Abe, Katsushi,Maekawa, Hiroaki,Arakawa, Hidetoshi
-
experimental part
p. 84 - 87
(2011/03/19)
-
- 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.
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-
Page/Page column 7-8
(2010/12/29)
-
- SYNTHESIS OF EQUOL
-
Subject of the invention is a method for the production of isoflavanes from isoflavones, whereby in a first reaction step (a) the 4-keto group of the isoflavone is reduced in a enantioselective manner, whilst the 2,3-double bond is maintained, to the 4-hydroxy compound.
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Page/Page column 11
(2010/04/03)
-
- Synthetic access to optically active isoflavans by using allylic substitution
-
A general approach to the (S)- and (R)-isoflavans was invented, and efficiency of the method was demonstrated by the synthesis of (S)-equol ((S)-3), (R)-sativan ((R)-4), and (R)-vestitol ((R)-5). The key step is the allylic substitution of (S)-6a (Ar1=2,4-(MeO)2C6H3) and (R)-6b (Ar1=2,4-(BnO)2C6H3) with copper reagents derived from CuBr·Me2S and Ar2-MgBr (7a, Ar2=4-MeOC6H4; 7b, 2,4-(MeO)2C6H3; 7c, 2-MOMO-4-MeOC6H3), furnishing anti SN2′ products (R)-8a and (S)-8b,c with 93-97% chirality transfer in 60-75% yields. The olefinic part of the products was oxidatively cleaved and the Me and Bn groups on the Ar1 moieties was then removed. Finally, phenol bromide 9a and phenol alcohols 9b,c underwent cyclization with K2CO3 and the Mitsunobu reagent to afford (S)-3 and (R)-4 and -5, respectively.
- Takashima, Yuji,Kaneko, Yuki,Kobayashi, Yuichi
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experimental part
p. 197 - 207
(2010/03/03)
-
- Synthesis of various kinds of isoflavones, isoflavanes, and biphenyl- ketones and their 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities
-
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
-
experimental part
p. 346 - 360
(2009/12/27)
-
- 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.
- Li, Sie-Rong,Chen, Po-Yuan,Chen, Liang-Yeu,Lo, Yi-Fang,Tsai, Ian-Lih,Wang, Eng-Chi
-
supporting information; experimental part
p. 2121 - 2123
(2009/07/26)
-
- 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.
- Thawornkuno, Charin,Tanaka, Michiko,Sone, Teruo,Asano, Kozo
-
experimental part
p. 1435 - 1438
(2009/12/06)
-
- Isolation and characterization of a novel equol-producing bacterium from human feces
-
An equol-producing bacterium was newly isolated from the feces of healthy humans and its morphological and biochemical properties were characterized. The cells were obligate anaerobes. They were non-sporulating, non-motile, gram-positive bacilliform bacteria with a pleomorphic morphology. The strain was catalase-positive, and oxidase-, urease-, and indole-negative. The only other sugar utilized by the strain was glycerin. The strain also degraded gelatin, but not esculin. It was most closely related to Eggerthella hongkongensis HKU10, with 93.3% 16S rDNA nucleotide sequence homology. Based on these features, the isolate was identified as a novel species of the genus Eggerthella. It was named Eggerthella sp. YY7918. Strain YY7918 converted substrates daidzein and dihydrodaidzein into S-equol, but did not convert daidzin, glysitein, genistein, or formononetin into it. An antimicrobial susceptibility assay indicated that strain YY7918 was susceptible to aminoglycoside-, tetracycline-, and new quinolone-antibiotics.
- Yokoyama, Shin-Ichiro,Suzuki, Tohru
-
body text
p. 2660 - 2666
(2009/04/06)
-
- New synthetic route to (S)-(-)-equol through allylic substitution
-
Allylic substitution of allylic picolinate 5 with a copper reagent derived from p-MeOC6H4MgBr (6) and CuBr·Me2S produced the anti SN2′ product 7 with high regioselectivity and efficient chirality transfer. Oxidative cleavage of the olefinic function to the alcohol followed by bromination afforded bromide 16, which upon demethylation and intramolecular ether ring formation furnished (S)-(-)-equol (3).
- Takashima, Yuji,Kobayashi, Yuichi
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p. 5156 - 5158
(2008/12/20)
-
- 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.
- Gupta, Atul,Ray, Suprabhat
-
experimental part
p. 3783 - 3786
(2009/06/17)
-
- 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.
- Gharpure, Santosh J.,Sathiyanarayanan,Jonnalagadda, Prasad
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p. 2974 - 2978
(2008/09/20)
-
- 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)
-
- 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 10-11
(2008/06/13)
-
- Total synthesis of (S)-equol
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The first enantioselective total synthesis of (S)-equol is reported. The described route relies on an Evans alkylation to form the stereocenter and an intramolecular Buchwald etherification to generate the chroman ring. Key features of this method include its brevity, its scalability, and the low cost of starting materials.
- Heemstra, Jennifer M.,Kerrigan, Sean A.,Doerge, Daniel R.,Helferich, William G.,Boulanger, William A.
-
p. 5441 - 5443
(2007/10/03)
-
- Production of isoflavone derivatives
-
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
-
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.
-
p. 1559 - 1567
(2007/10/03)
-
- Compositions and treatments for reducing potential unwanted side effects associated with long-term administration of androgenic testosterone precursors
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A method for reducing potential adverse effects of androgenic testosterone precursors by interfering with production or action of testosterone and estrogen metabolites by nutrient combinations is described. Although androgenic testosterone precursors themselves have little or no toxicity, there is the potential for their metabolites, estradiol and dihydrotestosterone, to enhance or cause hormone-responsive illnesses such as breast or prostatic cancer, benign prostatic hyperplasia, or hirsutism or acne in women. The use of the invented nutrient combinations reduces the formation or action of estradiol and dihydrotestosterone, thereby reducing potential adverse effects from increased production of these hormones following androgenic testosterone precursor administration. This may be accomplished without negating the effects of testosterone on muscle anabolism. The nutrient combinations include androstenedione, DHEA, pregnenolone, androstenediols, norandrostenedione and norandrostenediols, and natural products which reduce estrogen effects in the estrogen-responsive tissues, and substances to reduce formation of dihydrotestosterone from testosterone in prostate tissue.
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