2442-31-1

Basic information

• Product Name: 8-hydroxycoumarin
• Synonyms: 8-hydroxy-2H-chromen-2-one
• CAS NO: 2442-31-1
• Molecular Formula: C₉H₆O₃
• Molecular Weight: 162.14
• Mol File: 2442-31-1.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 361.573 °C at 760 mmHg
• Flash Point: 170.279 °C
• Appearance: /
• Density: 1.403 g/cm³
• Vapor Pressure: 9.86E-06mmHg at 25°C
• Refractive Index: 1.64
• CAS DataBase Reference: 8-hydroxycoumarin(CAS DataBase Reference)
• NIST Chemistry Reference: 8-hydroxycoumarin(2442-31-1)
• EPA Substance Registry System: 8-hydroxycoumarin(2442-31-1)

Safety Data

• Hazardous Substances Data: 2442-31-1(Hazardous Substances Data)

Usage

General Description

8-Hydroxycoumarin, also known as esculetin, is a chemical compound belonging to the coumarin family. Its structure consists of a benzene ring joined to a pyrone ring with a hydroxyl group at the 8th position. This hydroxylation at the 8th position significantly enhances its biological activities, making it more reactive and bioavailable. It occupies an important place in medicinal chemistry due to its various pharmacological properties, such as anti-inflammatory, antioxidant, anticoagulant, and anticancer effects. It also acts as a strong chelating agent for certain metal ions. However, like any chemical compound, it can be harmful if consumed or used in larger concentrations.

InChI:InChI=1/C9H6O3/c10-7-3-1-2-6-4-5-8(11)12-9(6)7/h1-5,10H

Upstream product

• 24677-78-9 2,3-dihydroxybenzaldehyde 
• 21204-67-1 methyl (triphenylphosphoranylidene)acetate 
• 617-48-1 malic acid 
• 120-80-9 benzene-1,2-diol 
• 13229-91-9 8-methoxy-2-oxo-2H-1-benzopyran-3-carbonitrile 
• 148-53-8 3-methoxy-2-hydroxybenzaldehyde 
• 1729-02-8 3-ethoxycarbonyl-8-methoxycoumarin 
• 2848-25-1 2-acetoxyphenol 
• 180694-45-5 8-Methoxymethoxy-chromen-2-one 
• 86-51-1 2,3-dimethyoxybenzaldehyde 
• 91-64-5 coumarin 
• 67985-75-5 2,3-diacetoxybenzaldehyde 
• 16139-79-0 ethyl diphenylphosphonoacetate 
• 7461-60-1 2,3-dimethoxycinnamic acid 

Downstream Products

• 38481-04-8 trans-2,3-dihydroxycinnamic acid 
• 855159-74-9 8-hydroxy-7-nitro-coumarin 
• 21524-16-3 8-methoxycoumarin 
• 1346436-18-7 C₃₄H₃₈O₁₁ 
• 1346436-17-6 C₃₄H₃₈O₁₁ 
• 1346436-08-5 C₁₄H₁₄O₅ 
• 1346436-07-4 C₁₄H₁₄O₅ 
• 30989-21-0 Amyrolin 
• 91368-56-8 7-allyl-8-hydroxy-2H-chromen-2-one 
• 109613-87-8 Carbonic acid 2-oxo-2H-chromen-8-yl ester 2-oxo-propyl ester 
• 96836-31-6 8-acetoxy-7-(1'-methyl-2',3'-dibromopropyl)coumarin 
• 96836-27-0 7-(1'-methylallyl)-8-acetoxycoumarin 
• 96836-23-6 8-hydroxy-7-(1'-methylallyl)coumarin 
• 4196-59-2 4',5'-dimethyl-pseudoisopsoralen 

Relevant articles and documents

CYP2A13-catalysed coumarin metabolism: Comparison with CYP2A5 and CYP2A6

1. We investigated the total metabolism of coumarin by baculovirus (BV)-expressed CYP2A13 and compared it with metabolism by BV-expressed CYP2A6. The major coumarin metabolite formed by CYP2A13 was 7-hydroxycoumarin, which accounted for 43% of the total metabolism. The product of 3,4-epoxidation, o-hydroxyphenylacetaldehyde (o-HPA), accounted for 30% of the total metabolites. 2. The Km and Vmax for CYP2A13-mediated coumarin 7-hydroxylation were 0.48 ± 0.07 μM and 0.15 ± 0.006 nmol min-1 nmol-1 CYP, respectively. The Vmax of coumarin 7-hydroxylation by CYP2A13 was about 16-fold lower than that of CYP2A6, whereas the Km was 10-fold lower. 3. In the mouse, there were two orthologues for CYP2A6: CYP2A4 and CYP2A5, which differed by only 11 amino acids. However, CYP2A5 is an efficient coumarin 7-hydroxylase, where as CYP2A4 is not. We report here that BV-expressed CYP2A4 metabolizes coumarin by 3,4-epoxidation. Two products of the 3,4-epoxidation pathway, o-HPA and o-hydroxyphenylacetic acid (o-HPAA), were detected by radioflow HPLC. 4. The Km and Vmax for the coumarin 3,4-epoxidation by CYP2A4 were 8.7 ± 3.6 μM and 0.20 ± 0.04nmol min-1 nmol-1 CYP, respectively. Coumarin 7-hydroxylation by CYP2A5 was more than 200 times more efficient than 3,4 epoxidation by CYP2A4.

Coumarin metabolism by rat esophageal microsomes and cytochrome P450 2A3

The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and it has been hypothesized that this tissue contains cytochrome P450 enzymes (P450s) which catalyze the metabolic activation of these carcinogens. The metabolic capacity of the esophagus is not well characterized. In the study described here, the products of 14C-coumarin metabolism by rat esophageal microsomes were identified and quantified. Metabolite characterization was by LC/MS/MS and GC/MS and comparison to standards, quantification was by radioflow HPLC. The coumarin metabolites formed by rat esophageal microsomes were compared to those formed by P450 2A3. The major metabolites formed by esophageal microsomes were 8-Hydroxycoumarin, o-Hydroxyphenylacetaldehyde (o-HPA), and o-hydroxyphenylacetic acid (o-HPAA). A smaller amount of 5-hydroxycoumarin, about one-third the 8-hydroxycoumarin, was also formed. o-HPA and o-HPAA are products of coumarin 3,4-epoxidation. The relative rates of coumarin 8-Hydroxylation and 3,4-epoxidation were similar. Coumarin 8-hydroxylation has not previously been reported as a major pathway in any tissue, and no P450s have yet been reported to catalyze this reaction. P450 2A3 catalyzed both the 7-hydroxylation and 3,4-epoxidation of coumarin. P450 2A3 was previously characterized as a coumarin 7-hydroxylase, however, in this study, we report that it catalyzes the formation of o-HPA more efficiently. The Km and Vmax were 1.3 ± 0.35 μM and 0.65 ± 0.06 nmol/min/nmol P450 for coumarin 7-hydroxylation and 1.4 ± 0.58 μM and 3.1 ± 0.46 nmol/min/nmol P450 for o-HPA formation.

Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for β-Arrestin-Biased D2R Agonists

By means of a formal structural hybridization of the antipsychotic drug aripiprazole and the heterocyclic catecholamine surrogates present in the β2-adrenoceptor agonists procaterol and BI-167107 (4), we designed and synthesized a collection of novel hydroxy-substituted heteroarylpiperazines and heteroarylhomopiperazines with high dopamine D2 receptor (D2R) affinity. In contrast to the weak agonistic behavior of aripiprazole, these ligands are capable of effectively mimicking those interactions of dopamine and the D2R that are crucial for an active state, leading to the recruitment of β-arrestin-2. Interestingly, some ligands show considerably lower intrinsic activity in guanine nucleotide exchange experiments at D2R and consequently represent biased agonists favoring β-arrestin-2 recruitment over canonical G protein activation. The ligands' agonistic properties are substantially driven by the presence of an endocyclic H-bond donor.

Synthesis and SAR studies of mono O-prenylated coumarins as potent 15-lipoxygenase inhibitors

All of the mono isopentenyloxy, -geranyloxy and -farnesyloxy derivatives of coumarin were synthesized and their inhibitory potency against soybean 15-lipoxygenase (SLO) and human 15-lipoxygenase-1 (HLO-1) were determined. Amongst the synthetic analogs, 5-farnesyloxycoumarin showed the most potent inhibitory activity against SLO (IC50 = 0.8 μM) while 6-farnesyloxycoumarin was the strongest HLO-1 inhibitor (IC50 = 1.3 μM). The IC50 variations of the farnesyl derivatives for HLO-1 (1.3 to ～75 μM) were much higher than that observed for SLO (0.8-5.8 μM). SAR studies showed that hydrogen bonding, CH/π, anion-π and S-OC interactions with FeIII-OH, Leu408, Glu357 and Met419 were the distinct intermolecular interactions which can lead to important role of the coumarin substitution site in HLO-1 inhibitory potency, respectively.

Silver-catalyzed facile decarboxylation of coumarin-3-carboxylic acids

A simple and highly efficient protocol with mild reaction conditions has been developed that allows the smooth protiodecarboxylation of diversely functionalized coumarin-3-carboxylic acids. In the presence of catalytic amounts of Ag2CO3 and acetic acid, even un-activated coumarin-3-carboxylic acids were converted in good to excellent yields and with great preparative ease to the corresponding coumarin derivatives.