479-13-0

Usage

Uses

Used in Pharmaceutical Industry:
Coumestrol is used as a pharmaceutical agent for its estrogenic activity. It can be utilized in the development of treatments for conditions related to estrogen deficiency or as a component in hormone replacement therapies.
Used in Research Applications:
Coumestrol is used as a research tool for studying the effects of estrogen on various biological processes. Its ability to bind to estrogen receptors makes it a valuable compound for investigating the mechanisms of estrogen action and for identifying potential therapeutic targets.
Used in Analytical Chemistry:
Due to its fluorescent properties, coumestrol can be used as a marker or indicator in analytical chemistry. Its distinct fluorescence in different pH environments allows for its use in experiments involving pH measurements or monitoring changes in solution acidity or alkalinity.
Used in Environmental Science:
Coumestrol's fluorescent characteristics can also be applied in environmental science for detecting and monitoring the presence of COUMESTROL in natural ecosystems, such as soil and water samples, where it may have an impact on the local flora and fauna.

Synthesis Reference(s)

Tetrahedron Letters, 4, p. 1151, 1963 DOI: 10.1039/jr9630005127

Biochem/physiol Actions

Coumestrol has anti-estrogenic actions in the brain and pituitary, mediated through estrogen receptor-α.

Safety Profile

An experimental teratogen. Other experimental reproductive effects. Mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

references

[1]. chen hy, dykstra kd, birzin et, et al. estrogen receptor ligands. part 1: the discovery of flavanoids with subtype selectivity. bioorg med chem lett. 2004 mar 22;14(6):1417-21.[2]. hopert ac, beyer a, frank k, et al. characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model. environ health perspect. 1998 sep;106(9):581-6.[3]. wang h, li h, moore lb, et al. the phytoestrogen coumestrol is a naturally occurring antagonist of the human pregnane x receptor. mol endocrinol. 2008 apr;22(4):838-57.

InChI:InChI=1/C15H8O5/c16-7-1-3-9-11(5-7)19-14-10-4-2-8(17)6-12(10)20-15(18)13(9)14/h1-6,16-17H

Upstream product

• 61503-83-1 3-(2,4-dimethoxyphenyl)-4-hydroxy-7-methoxy-1-benzopyran-2-one 
• 3172-99-4 Coumestrol dimethyl ether 
• 870456-45-4 2-(2,4-diacetoxyphenyl)-3-iodo-6-(tosyloxy)benzo[b]furan 
• 201230-82-2 carbon monoxide 
• 6626-15-9 4-Bromoresorcinol 
• 494773-45-4 4-bromo-3-hydroxy-phenyl 4-methyl-benzenesulfonate 
• 137396-01-1 4-bromo-3-methoxyphenyl 4-methylbenzenesulfonate 
• 328945-90-0 2-Methoxy-4-(tosyloxy)phenylacetylene 
• 328945-93-3 toluene-4-sulfonic acid 3-methoxy-4-trimethylsilanylethynyl-phenyl ester 
• 63604-94-4 2-bromo-5-methoxyphenol 
• 133730-24-2 1-Bromo-4-methoxy-2-(methoxymethoxy)benzene 
• 128980-54-1 C₁₇H₁₃IO₅ 
• 1855-30-7 1-(2,4-dihydroxyphenyl)-2-(2,4-dimethoxyphenyl)ethanone 
• 2150-41-6 methyl 2, 4-dimethoxybenzoate 

Downstream Products

• 3172-99-4 Coumestrol dimethyl ether 
• 185254-74-4 3,9-Bis-(tert-butyl-dimethyl-silanyloxy)-6-phenoxy-6H-benzo[4,5]furo[3,2-c]chromene 
• 3172-94-9 2-(2,4-dimethoxy-phenyl)-6-methoxy-benzofuran-3-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Synthesis of coumestrol and aureol

A total synthesis of coumestrol (1) and aureol (2) is described. The Perkin condensation of 2-bromo-4-hydroxylphenylacetic acid (6) and o-hydroxybenzaldehydes (7) gave the corresponding 2′-bromo-3-arylcoumarins (9). A copper-catalyzed consecutive hydroxylation and aerobic oxidative coupling of 9 under microwave conditions facilitated the total synthesis of 1 and 2, respectively, with spectroscopic data highly similar to those of natural products.

Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran

An unprecedented deconstructive reorganization strategy for the de novo synthesis of hydroxylated benzofurans from kojic acid- or maltol-derived alkynes is reported. In this reaction, both the benzene and furan rings were simultaneously constructed, whereas the pyrone moiety of the kojic acid or maltol was deconstructed and then reorganized into the benzene ring as a six-carbon component. Through this strategy, at least one free hydroxyl group was introduced into the benzene ring in a substitution-pattern tunable fashion without protection–deprotection and redox adjustment. With this method, a large number of hydroxylated benzofuran derivatives with different substitution-patterns have been prepared efficiently. This methodology has also been shown as the key step in a collective total synthesis of hydroxylated benzofuran-containing natural products (11 examples).

Copper-catalyzed intramolecular cross dehydrogenative coupling approach to coumestans from 2′-hydroxyl-3-arylcoumarins

A copper-catalyzed intramolecular cross dehydrogenative C-O coupling reaction of 2′-hydroxyl-3-arylcoumarins was developed. This protocol provided a facile and efficient strategy for the construction of natural coumestans and derivatives in moderate to high yields. This transformation exhibited good functional group compatibility and was amenable to substrates with free phenolic hydroxyl groups.

Method for preparing coumarino-heteroaromatic ring compounds and derivatives thereof through intramolecular cross-dehydrogenation coupling

The invention relates to a method for preparing coumarino-heteroaromatic ring compounds and derivatives thereof through intramolecular cross-dehydrogenation coupling. Specifically, compounds as shownin a formula Ia is subjected to intramolecular cross dehydrogenative coupling under the catalysis of palladium so as to prepare coumarin-heteroaromatic compounds as shown in a formula I, wherein groups in the formulas are as defined in the specification. The method is mild in reaction conditions, simple to operate, high in atom economy and applicable to a wide range of substrates, and high-yield preparation of multi-functionally substituted coumarin-heteroaromatic compounds and derivatives thereof is realized.

Synthetic method of polyhydroxy substituted coumestrol natural product

The invention discloses a synthetic method of a polyhydroxy substituted coumestrol natural product. 2-bromine-4-hydroxyphenylacetic acid serves as a raw material to make a condensation reaction with a hydroxy substituted salicylaldehyde compound, and a hydroxy substituted 3-(2-bromine-4-hydroxycyclohexyl phenyl)-7-hydroxy coumarin compound is obtained; and then a hydroxylation/oxidative coupling reaction is made under the condition of a catalyst and microwave heating, and the polyhydroxy substituted coumestrol natural product is obtained. The synthetic method is simple in route, easy and convenient to operate, high in yield, soft in reaction condition, free of needs of precious metal catalyzing, high in atom economy and low in cost, and multiple steps of cascade reactions are made simultaneously.

Collective Syntheses of 2-(3-Methylbenzofuran-2-yl)phenol-Derived Natural Products by a Cascade [3,3]-Sigmatropic Rearrangement/Aromatization Strategy

A cascade [3,3]-sigmatropic rearrangement/aromatization strategy to the synthesis of 2-(3-methylbenzofuran-2-yl)phenol derivatives was developed and applied to the collective syntheses of seven 2-arylbenzofuran-containing natural products, namely glycybenzofuran, glycyuralin E, lespedezol A1, puerariafuran, 7,2′,4′-trihydroxy-3-benzofurancarboxylic acid, coumestrol, and 4′-O-methylcoumestrol. Among them, the total syntheses of glycybenzofuran, glycyuralin E, puerariafuran, 7,2′,4′-trihydroxy-3-benzofurancarboxylic acid, and 4′-O-methylcoumestrol were reported for the first time. The practicality of this novel strategy in preparation of the key intermediates was demonstrated by performing the reaction on gram scale and by synthesizing a series of natural products with 2-(3-methylbenzofuran-2-yl)phenol scaffolds in a common strategy.

Copper-mediated synthesis of coumestans via C(sp2)-H functionalization: Protective group free route to coumestrol and 4′-O-methylcoumestrol

A simple and efficient two step synthesis of coumestans is described. The key reaction in the synthesis is the use of easily available Cu(OAc)2 for C[sbnd]H functionalization of 3-(2-hydroxyphenyl)coumarin to give coumestan ring system via formal oxidative cyclization. This approach provided a short protective group free route to naturally occurring coumestrol and 4′-O-methylcoumestrol.

Synthesis of Psoralidin derivatives and their anticancer activity: First synthesis of Lespeflorin I1

Synthetic scheme for the preparation of a number of different derivatives of anticancer natural product Psoralidin is described. A convergent synthetic approach is followed using simple starting materials like substituted phenyl acetic esters and benzoic acids. The developed synthetic route leads us to complete the first synthesis of an analogous natural product Lespeflorin I1, a mild melanin synthesis inhibitor. Preliminary bioactivity studies of the synthesized compounds are carried out against two commonly used prostate cancer cell lines. Results show that the bioactivity of the compounds can be manipulated by the simple modification of the functional groups.

COUMESTAN, COUMESTROL, COUMESTAN DERIVATIVES AND PROCESSES OF MAKING THE SAME AND USES OF SAME

The present invention provides new coumestans compounds and processes for the preparation of coumestans, pharmaceutical compositions having a coumestan as an active pharmaceutical ingredient, and methods of utilizing coumestans as selective estrogen receptor modulators (SERMs) for treating estrogen dependent diseases such as breast cancer.

Aerobic iron-based cross-dehydrogenative coupling enables efficient diversity-oriented synthesis of coumestrol-based selective estrogen receptor modulators

An iron-based cross-dehydrogenative coupling (CDC) approach was applied for the diversity-oriented synthesis of coumestrol-based selective estrogen receptor modulators (SERMs), representing the first application of CDC chemistry in natural product synthesis. The first stage of the two-step synthesis of coumestrol involved a modified aerobic oxidative cross-coupling between ethyl 2-(2,4-dimethoxybenzoyl)acetate and 3-methoxyphenol, with FeCl3 (10 mol %) as the catalyst. The benzofuran coupling product was then subjected to sequential deprotection and lactonization steps, affording the natural product in 59 % overall yield. Based on this new methodology other coumestrol analogues were prepared, and their effects on the proliferation of the estrogen receptor (ER)-dependent MCF-7 and of the ER-independent MDA-MB-231 breast cancer cells were tested. As a result, new types of estrogen receptor ligands having an acetamide group instead of the 9-hydroxyl group of coumestrol were discovered. Both 9-acetamido-coumestrol and 8-acetamidocoumestrol were found more active than the natural product against estrogen-dependent MCF-7 breast cancer cells, with IC50 values of 30 and 9 nM, respectively. Green medicinal chemistry: An iron-based cross-dehydrogenative coupling (CDC) approach was applied for the diversity-oriented synthesis of coumestrol-based selective estrogen receptor modulators (SERMs), representing the first application of CDC chemistry in natural product synthesis (see scheme; DCE=dichloroethane). Copyright