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1.
Chem Pharm Bull (Tokyo) ; 69(1): 99-105, 2021.
Article in English | MEDLINE | ID: mdl-33390527

ABSTRACT

A set of isoflavononid and flavonoid analogs was prepared and evaluated for estrogen receptor α (ERα) and ERß 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 ERß, 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/ß agonists with ERß 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.


Subject(s)
Estrogen Receptor alpha/agonists , Estrogen Receptor beta/agonists , Neuroprotective Agents/pharmacology , Phytoestrogens/pharmacology , Animals , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Docking Simulation , Molecular Structure , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/chemistry , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Phytoestrogens/chemical synthesis , Phytoestrogens/chemistry , Structure-Activity Relationship
2.
Sci Rep ; 7(1): 12445, 2017 09 29.
Article in English | MEDLINE | ID: mdl-28963488

ABSTRACT

Prenylated flavonols are known as phytoestrogen and have good bioactivties. However, their abundances in nature are pretty low. It is required to find an efficient synthesis technique. Icariin is a prenylated flavonol glycoside with low cost. It can be used to synthesize different prenylated flavonols. A combination of cellulase and trifluoacetic acid hydrolysis could effectively remove rhamnose and glucose from icariin. Icaritin, anhydroicaritin and wushanicaritin were the leading prenylated flavonol products. Their affinities to estrogen receptors α and ß were predicted by docking study. The weak affinity of wushanicaritin indicated that prenyl hydroxylation impaired its affinity to estrogen receptor ß. The prenyl cyclization led to a loss of affinity to both receptors. The interactions between icaritin and ligand binding cavity of estrogen receptor ß were simulated. π-π stacking and hydrophobic forces were predicted to be the dominant interactions positioning icaritin, which induced the helix (H12) forming an activated conformation.


Subject(s)
Benzopyrans/chemical synthesis , Estrogen Receptor alpha/chemistry , Estrogen Receptor beta/chemistry , Flavonoids/chemistry , Flavonoids/chemical synthesis , Phytoestrogens/chemical synthesis , Benzopyrans/chemistry , Binding Sites , Cellulase/chemistry , Estrogen Receptor alpha/agonists , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/agonists , Estrogen Receptor beta/metabolism , Glucose/chemistry , Hydrolysis , Hydrophobic and Hydrophilic Interactions , Hydroxylation , Models, Molecular , Molecular Docking Simulation , Phytoestrogens/chemistry , Prenylation , Protein Binding , Protein Structure, Secondary , Rhamnose/chemistry , Trifluoroacetic Acid/chemistry
3.
J Org Chem ; 80(19): 9740-66, 2015 Oct 02.
Article in English | MEDLINE | ID: mdl-26398568

ABSTRACT

An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenters in this family of molecules, and the reactions developed en route to paspaline present a series of new synthetic disconnections in preparing steroidal natural products.


Subject(s)
Biological Products/chemistry , Biological Products/chemical synthesis , Diterpenes/chemistry , Diterpenes/chemical synthesis , Indole Alkaloids/chemical synthesis , Indoles/chemistry , Indoles/chemical synthesis , Phytoestrogens/chemical synthesis , Indole Alkaloids/chemistry , Molecular Structure , Phytoestrogens/chemistry , Stereoisomerism
4.
Eur J Med Chem ; 85: 107-18, 2014 Oct 06.
Article in English | MEDLINE | ID: mdl-25078314

ABSTRACT

A series of azaisoflavone analogs were designed and synthesized and their transactivation activities and binding affinities for ERα and ERß were investigated. Among these compounds, 2b and 3a were the most potent with 6.5 and 1.1 µM of EC50, respectively. Molecular modeling study showed putative binding modes of the compound 3a in the active site of ERα and ERß, which were similar with that of genistein and provided insight of the effect of N-alkyl substitution of azaisoflavones on ERß activity. Also, a biphasic effect of azaisoflavone analogs on MCF-7 cell growth depending on their concentrations was investigated.


Subject(s)
Drug Design , Flavones/chemical synthesis , Flavones/pharmacology , Phytoestrogens/chemical synthesis , Phytoestrogens/pharmacology , Quinolones/chemical synthesis , Quinolones/pharmacology , Catalytic Domain , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Dose-Response Relationship, Drug , Estrogen Receptor alpha/chemistry , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/chemistry , Estrogen Receptor beta/genetics , Estrogen Receptor beta/metabolism , Flavones/chemistry , Flavones/metabolism , Humans , MCF-7 Cells , Molecular Docking Simulation , Phytoestrogens/chemistry , Phytoestrogens/metabolism , Quinolones/chemistry , Quinolones/metabolism , Structure-Activity Relationship , Transcriptional Activation/drug effects
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 85(1): 298-302, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22041503

ABSTRACT

In the present work the feasibility of ß-cyclodextrin in complexation was explored, as a tool for improving the solubility and biological ability of daidzein derivatives. A series of phosphorylated daidzein derivatives featuring different chain lengths were synthesized through a modified Atherton-Todd reaction and their inclusion complexes with ßCD were prepared by coprecipitation method. The inclusion complexation behavior was studied by fluorescence, UV, FT-IR, MS and (1)H NMR. The results showed that only phosphorylated daidzein derivative carrying small substituent group ((C(2)H(5)O)(2)PO) entered the cavity of ßCD and formed 1:1 inclusion complex. The formation constant was 175(mol/L)(-1).


Subject(s)
Isoflavones/chemistry , Phytoestrogens/chemistry , beta-Cyclodextrins/chemistry , Isoflavones/chemical synthesis , Magnetic Resonance Spectroscopy , Phosphorylation , Phytoestrogens/chemical synthesis , Solubility , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared
7.
Bioorg Med Chem Lett ; 21(2): 677-81, 2011 Jan 15.
Article in English | MEDLINE | ID: mdl-21194940

ABSTRACT

A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of osteoblasts. Further, these three compounds did not show any estrogen agonistic activity, however had mild estrogen antagonistic effect. Out of the three compounds, 3c was found to maximally increase the mineralization of bone marrow osteoprogenitor cells. Compound 3c also robustly increased the mRNA levels of osteogenic genes including bone morphogenetic protein-2 and osteocalcin in osteoblasts. Unlike daidzein, 3c did not inhibit osteoclastogenesis. Collectively, we demonstrate osteogenic activity of daidzein analogs at significantly lower concentrations than daidzein.


Subject(s)
Cell Differentiation/drug effects , Isoflavones/chemistry , Isoflavones/pharmacology , Osteoblasts/drug effects , Phytoestrogens/chemistry , Phytoestrogens/pharmacology , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Bone Morphogenetic Protein 2/genetics , Calcification, Physiologic/drug effects , Cells, Cultured , Gene Expression Regulation/drug effects , Isoflavones/chemical synthesis , Osteoblasts/cytology , Osteoblasts/metabolism , Osteocalcin/genetics , Phytoestrogens/chemical synthesis , RNA, Messenger/genetics , Rats , Skull/cytology
8.
Nutrients ; 2(3): 340-54, 2010 03.
Article in English | MEDLINE | ID: mdl-22254026

ABSTRACT

Equol, one of the main metabolites of daidzein, is a chiral compound with pleiotropic effects on cellular signaling. This property may induce activation/inhibition of the estrogen receptors (ER) a or b, and therefore, explain the beneficial/deleterious effects of equol on estrogen-dependent diseases. With its asymmetric centre at position C-3, equol can exist in two enantiomeric forms (R- and S-equol). To elucidate the yet unclear mechanisms of ER activation/inhibition by equol, we performed a comprehensive analysis of ERa and ERb transactivation by racemic equol, as well as by enantiomerically pure forms. Racemic equol was prepared by catalytic hydrogenation from daidzein and separated into enantiomers by chiral HPLC. The configuration assignment was performed by optical rotatory power measurements. The ER-induced transactivation by R- and S-equol (0.1-10 µM) and 17b-estradiol (E2, 10 nM) was studied using transient transfections of ERα and ERß in CHO, HepG2 and HeLa cell lines. R- and S-equol induce ER transactivation in an opposite fashion according to the cellular context. R-equol and S-equol are more potent in inducing ERα in an AF-2 and AF-1 permissive cell line, respectively. Involvement of ERα transactivation functions (AF-1 and AF-2) in these effects has been examined. Both AF-1 and AF-2 are involved in racemic equol, R-equol and S-equol induced ERα transcriptional activity. These results could be of interest to find a specific ligand modulating ER transactivation and could contribute to explaining the diversity of equol actions in vivo.


Subject(s)
Equol/pharmacology , Phytoestrogens/pharmacology , Receptors, Estrogen/drug effects , Transcriptional Activation/drug effects , Equol/chemical synthesis , Estrogen Receptor alpha/drug effects , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/drug effects , Estrogen Receptor beta/metabolism , Humans , Phytoestrogens/chemical synthesis , Receptors, Estrogen/metabolism
9.
J Cell Biochem ; 108(2): 388-99, 2009 Oct 01.
Article in English | MEDLINE | ID: mdl-19598169

ABSTRACT

Following a lead obtained from stem-bark extract of Butea monosperma, two structurally related methoxyisoflavones; cajanin and isoformononetin were studied for their effects in osteoblasts. Cajanin had strong mitogenic as well as differentiation-promoting effects on osteoblasts that involved subsequent activation of MEK-Erk and Akt pathways. On the other hand, isoformononetin exhibited potent anti-apoptotic effect in addition to promoting osteoblast differentiation that involved parallel activation of MEK-Erk and Akt pathways. Unlike genistein or daidzein, none of these two compounds appear to act via estrogen receptors in osteoblast. Once daily oral (by gavage) treatment for 30 consecutive days was given to recently weaned female Sprague-Dawley rats with each of these compounds at 10.0 mg kg(-1) day(-1) dose. Cajanin increased bone mineral density (BMD) at all skeletal sites studied, bone biomechanical strength, mineral apposition rate (MAR) and bone formation rate (BFR), compared with control. BMD levels at various anatomic positions were also increased with isoformononetin compared with control however, its effect was less potent than cajanin. Isoformononetin had no effect on the parameters of bone biomechanical strength although it enhanced MAR and BFR compared with control. Isoformononetin had very mild uterotrophic effect, whereas cajanin was devoid of any such effect. Our data suggest that cajanin is more potent than isoformononetin in accelerating peak bone mass achievement. To the best of our knowledge, this work represents the first attempt to elucidate structure-activity relationship between the two methoxylated isoflavones regarding their effects in osteoblasts and bone formation.


Subject(s)
Diethylstilbestrol/analogs & derivatives , Genistein/analogs & derivatives , Isoflavones/pharmacology , MAP Kinase Signaling System , Osteogenesis , Phytoestrogens/pharmacology , Aging , Analysis of Variance , Animals , Apoptosis , Bone Density , Bone Marrow Cells/metabolism , Bone and Bones/metabolism , Calcification, Physiologic , Cell Differentiation , Cell Proliferation , Cells, Cultured , Diethylstilbestrol/administration & dosage , Diethylstilbestrol/chemical synthesis , Diethylstilbestrol/pharmacology , Enzyme Inhibitors/metabolism , Estrogen Antagonists/metabolism , Estrogen Receptor Modulators/metabolism , Estrogens/metabolism , Female , Isoflavones/administration & dosage , Isoflavones/chemical synthesis , Osteoblasts/metabolism , Phytoestrogens/administration & dosage , Phytoestrogens/chemical synthesis , Rats , Rats, Sprague-Dawley , Uterus/cytology , Uterus/metabolism
10.
Steroids ; 72(13): 851-4, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17727908

ABSTRACT

The first synthesis of daidzein 7-O-beta-D-glucuronide-4'-O-sulfate, a mixed conjugate of an important dietary phytoestrogen is described.


Subject(s)
Isoflavones/chemistry , Phytoestrogens/chemical synthesis
11.
Arch Pharm (Weinheim) ; 340(7): 372-6, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17610303

ABSTRACT

Four prenylflavonoids, bavachin 1, isobavachin 2, 7,4'-dihydroxy-8-prenylflavone 3, and 8-prenylapigenin 4 were synthesized and recognized for possessing estrogen-like activity in MCF-7/BOS cells, as evaluated by an estrogen-screening assay. All compounds significantly stimulated the proliferation of MCF-7/BOS cells in a dose-dependent manner. Isobavachin 2 showed the most potent activity, while bavachin 1 was the weakest. The estrogenic potency of these compounds is ranked as follows: 2 > 4 > 3 > 1.


Subject(s)
Flavonoids/chemical synthesis , Flavonoids/pharmacology , Phytoestrogens/chemical synthesis , Phytoestrogens/pharmacology , Cell Line, Tumor , Flavonoids/chemistry , Humans , Phytoestrogens/chemistry
12.
J Med Chem ; 49(25): 7357-65, 2006 Dec 14.
Article in English | MEDLINE | ID: mdl-17149865

ABSTRACT

In search of therapeutic agents for estrogen-related pathologies, phytoestrogens are being extensively explored. In contrast to naringenin, 8-prenylnaringenin is a potent hop-derived estrogenic compound, highlighting the importance of the prenyl group for hormonal activity. We investigated the effects of substituting the prenyl group at C(8) with alkyl chains of varying lengths and branching patterns on estrogen receptor (ER) subtype ERalpha- and ERbeta-binding affinities and transcriptional activities. In addition, features of the ligand-induced receptor conformations were explored using a set of specific ER-binding peptides. The new 8-alkylnaringenins were found to span an activity spectrum ranging from full agonism to partial agonism to antagonism. Most strikingly, 8-(2,2-dimethylpropyl)naringenin exhibited full agonist character on ERalpha, but pronounced antagonist character on ERbeta. Knowledge on how ER-subtype-selective activities can be designed provides valuable information for future drug or tool compound discovery.


Subject(s)
Estrogen Receptor alpha/agonists , Estrogen Receptor alpha/antagonists & inhibitors , Estrogen Receptor beta/agonists , Estrogen Receptor beta/antagonists & inhibitors , Flavanones/chemical synthesis , Phytoestrogens/chemical synthesis , Binding, Competitive , Cell Line, Tumor , Estrogen Receptor alpha/chemistry , Estrogen Receptor beta/chemistry , Flavanones/chemistry , Flavanones/pharmacology , Humans , Hydrophobic and Hydrophilic Interactions , Models, Molecular , Phytoestrogens/chemistry , Phytoestrogens/pharmacology , Protein Conformation , Radioligand Assay , Structure-Activity Relationship , Transcription, Genetic , Two-Hybrid System Techniques
13.
Rev. esp. enferm. metab. óseas (Ed. impr.) ; 15(5): 91-97, sept. 2006. ilus
Article in Spanish | IBECS | ID: ibc-79182

ABSTRACT

Introducción. Estudios epidemiológicos sugieren que los fitoestrógenos de la soja podrían ser responsables de la baja incidencia del carcinoma prostático (CaP) en poblaciones asiáticas. Las células de CaP expresan factores reguladores de la proliferación/viabilidad celular, así como factores capaces de interaccionar con las células en el microambiente óseo. En el presente estudio hemos evaluado los efectos de los fitoestrógenos de la soja, genisteína y daidzeína, sobre la viabilidad celular/apoptosis y sobre la expresión de la proteína relacionada con la parathormona (PTHrP) y su receptor (PTH1R), la osteoprotegerina (OPG) y el ligando del receptor activador del NF-kappa B (RANKL) en las células de CaP humano PC-3 y LNCaP. Pacientes y métodos. Las células, sembradas a 20.000 células/cm2 en RPMI con suero fetal bovino al 10%, se incubaron con distintas concentraciones de cada fitoestrógeno o el vehículo salino (control basal) durante 1-4 días. La viabilidad celular se evaluó por exclusión con azul de tripán y la apoptosis se determinó por citometría de flujo. La expresión génica de PTHrP se analizó por RT-PCR semicuantitativa con cebadores específicos. La expresión proteica de PTHrP, PTH1R, OPG y RANKL se determinó por transferencia western en extractos de proteína celular total o de membrana (RANKL). Resultados. Hemos encontrado que tanto la genisteína como la daidzeína en el rango µM disminuyen la viabilidad celular e incrementan la apoptosis; siendo la genisteína más potente y eficaz que la daidzeína en ambos tipos celulares. Además, estas isoflavonas a dosis ¾ nM aumentan la expresión de PTHrP y del PTH1R, así como la relación OPG/RANKL en estas células. Conclusiones. Estos hallazgos demuestran que diferentes dosis de genisteína y daidzeína inducen efectos diversos sobre las células de CaP que podrían afectar al desarrollo de este tumor(AU)


Introduction. Epidemiological studies suggest that soy phytoestrogens might be responsible for the low incidence of prostate carcinoma (PCa) in Asian populations. PCa cells express regulatory factors of cell proliferation and viability, and also several factors that interact with cells in the bone microenvironment. In the present study, we evaluated the effects of soy phytoestrogens genistein and daidzein on cell viability and apoptosis, and also on the expression of parathormone-related protein (PTHrP) and its receptor (PTH1R), osteoprotegerina (OPG) and receptor activator of nuclear factor kappa B ligand (RANK-L) in the human PCa cell lines PC-3 and LNCaP. Patients and methods. Cells were seeded at 20,000 cells/cm2 in RPMI with 10% fetal bovine serum, and then were incubated with different concentrations of each phytoestrogen or saline vehicle (basal control) for 1-4 days. Cell viability was evaluated by Trypan blue exclusion, and apoptosis was determined by flow citometry. Gene expression of PTHrP was analyzed by semiquantitative RT-PCR with specific primers. Protein expression of PTHrP, the PTH1R, OPG, and RANKL was determined by western blot in total cell protein or cell membrane (RANKL) extracts. Results. We found that both genistein and daidzein, at µM range, decrease cell viability and increase apoptosis; but genistein was more potent and efficient than daidzein in both PCa cell lines. In addition, these isoflavones, at ¾ nM, increase the expression of PTHrP and the PTH1R, and also the OPG/RANKL ratio in these cells. Conclusions. These findings demonstrate that different concentrations of genistein and daidzein induce distinct effects on PCa cells that might affect PCa development(AU)


Subject(s)
Humans , Male , Female , Phytoestrogens/adverse effects , Prostatic Neoplasms/epidemiology , Glycine max/adverse effects , Genistein/therapeutic use , Apoptosis/physiology , Cellular Apoptosis Susceptibility Protein/chemical synthesis , Osteoprotegerin/therapeutic use , Flow Cytometry/methods , Flow Cytometry/trends , Gene Expression/physiology , Cell Survival/physiology , Gene Expression/genetics , Phytoestrogens/chemical synthesis , Phytoestrogens/therapeutic use , Gene Expression/immunology , Gene Expression Profiling/methods , Gene Expression Profiling , Blotting, Western/trends , Blotting, Western
14.
Neuropharmacology ; 49(1): 86-96, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15992583

ABSTRACT

In search of novel therapeutic approaches for Alzheimer's disease (AD), we report herein the identification, design, synthesis, and pharmacological activity of (4-ethyl-piperaz-1-yl)-phenylmethanone derivatives with neuroprotective properties against beta-amyloid-induced toxicity. (4-ethyl-piperaz-1-yl)-phenylmethanone is a common substructure shared by molecules isolated from plants of the Asteraceae genus, traditionally used as restorative of lost or declining mental functions. (4-Ethyl-piperaz-1-yl)-phenylmethanone displayed strong neuroprotective properties against Abeta1-42 and reversed Abeta1-42-induced ATP depletion on neuronal cells, suggesting a mitochondrial site of action. Abeta1-42 has been described to induce a hyperactivity of the glutamate network in neuronal cells. (4-Ethyl-piperaz-1-yl)-phenylmethanone also inhibited the neurotoxic effect that glutamate displayed on PC12 cells, suggesting that the reduction of glutamate-induced neurotoxicity may be one of the mechanisms by which this compound exerts its neuroprotective properties against the deleterious effects of the Abeta1-42. These data suggest that the identified (4-ethyl-piperaz-1-yl)-phenylmethanone chemical entity exerts neuroprotective properties and may serve as a lead compound for the development of novel therapies for AD.


Subject(s)
Amyloid beta-Peptides/toxicity , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/pharmacology , Phytoestrogens/chemical synthesis , Phytoestrogens/pharmacology , Adenosine Triphosphate/metabolism , Analysis of Variance , Animals , Cell Survival/drug effects , Chromatography, Thin Layer/methods , Dizocilpine Maleate/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Free Radicals/metabolism , PC12 Cells , Peptide Fragments/toxicity , Piperazines/chemical synthesis , Piperazines/pharmacology , Plant Preparations , Rats , Tetrazolium Salts , Thiazoles
15.
J Med Chem ; 48(10): 3463-6, 2005 May 19.
Article in English | MEDLINE | ID: mdl-15887952

ABSTRACT

ERbeta has been associated with estrogen-induced promotion of memory function and neuronal survival. Based on the optimized complex structure of human ERbeta LBD bound with genistein, computer-aided structure-based virtual screening against a natural source chemical database was conducted to determine the occurrence of plant-based ERbeta-selective ligands. Twelve representative hits derived from database screening were assessed for their binding profiles to both ERs, three of which displayed over 100-fold binding selectivity to ERbeta over ERalpha.


Subject(s)
Estrogen Receptor beta/chemistry , Neuroprotective Agents/chemical synthesis , Phytoestrogens/chemical synthesis , Plants/chemistry , Aging , Benzopyrans/chemical synthesis , Benzopyrans/chemistry , Binding Sites , Binding, Competitive , Databases, Factual , Estrogen Receptor alpha/chemistry , Fluorescence Polarization , Genistein/chemistry , Humans , Ligands , Models, Molecular , Neurodegenerative Diseases/drug therapy , Neuroprotective Agents/chemistry , Phytoestrogens/chemistry , Protein Conformation , Quantitative Structure-Activity Relationship
16.
Org Biomol Chem ; 3(4): 674-81, 2005 Feb 21.
Article in English | MEDLINE | ID: mdl-15703807

ABSTRACT

A convergent synthesis of kwakhurin (5), a characteristic estrogen-like isoflavone of Pueraria mirifica(Leguminosae), is described. Isoflavone skeleton 31 was constructed by Suzuki-Miyaura coupling of 3-bromochromone 26 (AC-ring) and arylboronic acid 30 (B-ring) in the presence of TBAB as an additive. Microwave-assisted coupling was also examined, but did not improve the yield. Baeyer-Villiger oxidation, followed by propargylation and reduction afforded 1,1-dimethylallyl ether 37. 6'-Prenylisoflavone 34 was obtained in high yield by Claisen rearrangement of 37 in N,N-diethylaniline. On the other hand, 1,3-rearrangement of prenyl ether 33 with clay gave 34 in poor yield. Successive methylation of 34 and deprotection yielded the target kwakhurin (5) in 12% overall yield from 2,4-dihydroxybenzaldehyde (23).


Subject(s)
Isoflavones/chemical synthesis , Phytoestrogens/chemical synthesis , Pueraria/chemistry , Boronic Acids/chemistry , Chromones/chemistry , Heterocyclic Compounds, 3-Ring/chemical synthesis , Heterocyclic Compounds, 3-Ring/chemistry , Isoflavones/chemistry , Methylation , Molecular Structure , Oxidation-Reduction , Phytoestrogens/chemistry
17.
Steroids ; 69(10): 613-6, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15465105

ABSTRACT

Di-O-sulfates of six phytoestrogenic isoflavonoids, daidzein (1), genistein (2), glycitein (3), and the reduced metabolites dihydrodaidzein (4), dihydrogenistein (5) and equol (6) were synthesized. These compounds are known or potential inhibitors of steroid sulfatase enzymes. The new compounds were characterized by NMR and mass spectrometry.


Subject(s)
Isoflavones/chemical synthesis , Phytoestrogens/chemical synthesis , Sulfuric Acid Esters/chemical synthesis , Equol , Genistein/analogs & derivatives , Genistein/chemistry , Isoflavones/chemistry , Magnetic Resonance Spectroscopy , Phytoestrogens/chemistry , Steryl-Sulfatase/antagonists & inhibitors , Sulfuric Acid Esters/chemistry
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