Product name: 7-O-Methyleriodictyol
Synonym name: Sterubin; Eriodictyol 7-methyl ether; 7-Methoxy-3',4',5-trihydroxyflavanone
Catalogue No.: SBP02141
Cas No.: 51857-11-5
Formula: C₁₆H₁₄O₆
Mol Weight: 302.282
Botanical Source:
Physical Description: Powder
Type of Compound: Flavonoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.

For Reference Standard and R&D, Not for Human Use Directly.

HPLC of 7-O-Methyleriodictyol

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Natural products, as an important source of drug lead compounds, play an irreplaceable role in the long history of human struggle against diseases. Among them, flavonoids have always been a hot topic in medicinal chemistry and pharmacology research due to their extensive biological activity and relatively low adverse reactions. Eriodictyol, as a natural dihydroflavonoid compound, mainly exists in plants such as lemon and rosemary, and has been proven to have various pharmacological activities such as antioxidant, anti-inflammatory, and neuroprotective effects. However, natural flavonoids generally suffer from poor metabolic stability and low bioavailability, which limits their clinical translation. Structural modification, especially methylation, is one of the effective strategies to improve its drug properties, enhance or endow new biological activities.

7-O-Methyliodictyol (CAS number: 51857-11-5) is a derivative of resveratrol whose 7-hydroxyl group has been methylated. This small structural change not only significantly affects the physicochemical properties of the molecule, such as lipid solubility and metabolic stability, but may also profoundly alter its interaction mode with biological targets. Although 7-O-methyl coumarin is less well-known among the public and some research fields compared to its parent compound coumarin, in recent years, with the deepening of research on natural methylated flavonoids, its unique pharmacological activity, especially its potential value in antioxidant stress-related diseases, is gradually being revealed. This article aims to provide a systematic review of the chemical properties, plant sources, pharmacological activities, mechanisms of action, and potential medicinal properties of 7-O-methylcatechol, in order to provide comprehensive academic references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The chemical essence of 7-O-methyl coumarin is the product of replacing the hydroxyl group at position 7 of coumarin (5,7,3 ', 4' - tetrahydroxydihydroflavone) with a methoxy group (- OCH ∝). Its system is named (S) -2- (3,4-dihydroxyphenyl) -5-hydroxy-7-methoxy-2,3-dihydrochrom-4-one. Structurally, it retains the C6-C3-C6 basic skeleton of dihydroflavones, where the C-5 position of the A ring is a hydroxyl group and the C-7 position is a methoxy group; The C-3 'and C-4' positions of the B ring are adjacent dihydroxy structures; The C-ring is a saturated pyranone ring, and the C-2 position is the chiral center.

The molecular formula of this compound is C ₁₆ H ₁₄ O ₆, with a molecular weight of 302.2820. The key physicochemical parameters are as follows: the lipid water partition coefficient (LogP) is 2.2986, indicating that it has a certain lipophilicity, which is conducive to its penetration of the cell membrane; The polar surface area (TPSA) is 96.2200 Å ², which is at a moderate level, indicating that it may have good oral absorption potential, but may also be affected by intestinal efflux transporters. The water solubility (LogS) of the compound is 0.2227, indicating poor water solubility, which may be a potential limiting factor for its low bioavailability in vivo. In addition, the predictive model shows that its blood-brain barrier (BBB) penetration ability is low, suggesting that it may be limited in exerting its central nervous system function, but at the same time, it may also imply a lower risk of central adverse reactions. The prediction result of hERG inhibition is' no ', indicating a low risk of inducing QT interval prolongation and arrhythmia in the heart. The Ames test predicted a value of 0.6, indicating a certain risk of mutagenicity, but further experimental verification is needed.

Compared with the parent compound, the methylation of the 7-hydroxyl group blocks a key phenolic hydroxyl group. This modification usually brings about the following changes: firstly, an increase in the lipophilicity of the molecule (LogP), which helps to improve its affinity with biofilms and transmembrane transport ability; Secondly, it shields the 7-hydroxyl group, avoiding its binding reaction with glucuronic acid or sulfuric acid, which may improve metabolic stability and prolong the half-life in vivo; Finally, the hydrogen bond donor/acceptor mode between the molecule and target proteins (such as enzymes or receptors) has been altered, which may affect the strength and selectivity of their biological activity.

Plant sources and extraction methods

7-O-methylcatechol is not a widely distributed common flavonoid, and its natural sources are relatively limited, mainly found in certain specific plant families and genera. The plants currently reported to contain this compound mainly include:

1. Asteraceae plants For example, in Chromolaena odorata(Airplane Grass) and Eupatorium Some plants belonging to the genus have been isolated and identified. These plants are often used in traditional medicine to treat wounds, inflammation, and other conditions.
2. Lamiaceae plants: Some rosemary（Rosmarinus officinalis）Or sage（Salvia The extract of spp may also contain trace amounts of 7-O-methyl coumarin.
3. Rutaceae plants As a rich source of coumarin, its methylated derivatives may also exist in citrus fruits such as lemons, although the content is usually much lower than that of coumarin.
4. Fabaceae plants It has also been found in some medicinal leguminous plants.

Given its typically low content in plants, efficient modern chromatographic techniques are required for the extraction, separation, and purification of 7-O-methylcatechol. The typical extraction process is as follows:

1. Raw material pretreatment Crush and sieve dry plant materials (such as leaves and whole grass).
2. Solvent extraction Typically, polar organic solvents such as methanol, ethanol, or their aqueous solutions are used for extraction. To improve extraction efficiency, ultrasound assisted extraction (UAE) or heating reflux extraction can be used.
3. Preliminary purification After the extraction solution is concentrated under reduced pressure, crude extract is obtained. The crude extract can be preliminarily segmented by liquid-liquid extraction (such as extraction with petroleum ether, ethyl acetate, and n-butanol in sequence), and 7-O-methylcatechol is usually enriched in the ethyl acetate extraction site.
4. chromatographic separation This is a crucial step in obtaining high-purity compounds. Common methods include:
   • Silica gel column chromatography Use solvent systems such as chloroform methanol or petroleum ether acetone for gradient elution.
   • Sephadex LH-20 gel column chromatography Using molecular sieves to further remove pigments and other impurities.
   • Preparation type high-performance liquid chromatography (Pre HPLC)Using a reverse phase C18 column, acetonitrile water or methanol water (often with a small amount of formic acid or acetic acid added) is used as the mobile phase for high-purity separation.

Finally, the isolated compound was structurally identified using techniques such as nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), confirming its identity as 7-O-methylcatechol.

Pharmacological activity research

At present, research on the pharmacological activity of 7-O-methylprednisolone mainly focuses on the antioxidant field similar to its parent compound, but also shows some unique advantages.

antioxidant activity

Antioxidant activity is the most core and extensively studied pharmacological activity of 7-O-methylcatechol. Oxidative stress is the common pathological basis for the occurrence and development of many chronic diseases (such as cardiovascular disease, neurodegenerative disease, diabetes, cancer). The antioxidant effect of 7-O-methyl coumarin is reflected in multiple aspects:

1. Directly eliminate free radicals The B-ring hydroxyl group (3 ', 4' - dihydroxy) in its molecular structure is an excellent hydrogen atom donor, which can directly neutralize reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as hydroxyl radicals (· OH), superoxide anions (O ₂⁻ ·), peroxynitrite (ONOO ⁻), etc. In vitro chemical experiments (such as DPPH, ABTS, FRAP methods) have confirmed its strong free radical scavenging and reducing abilities.
2. Chelate transition metal ions The ortho dihydroxy and 5-hydroxy-4-keto structural units in its structure can chelate iron ions (Fe ² ⁺/Fe ³ ⁺) and copper ions (Cu ² ⁺), thereby inhibiting the Fenton reaction and reducing the generation of highly active hydroxyl radicals.
3. Activate endogenous antioxidant defense system This is the key to its long-lasting antioxidant effect. Research has shown that 7-O-methylcatechol can activate the nuclear factor E2 related factor 2 (NFE2L2/NRF2) signaling pathway. NRF2 is the main transcription factor that regulates the expression of intracellular antioxidant and detoxification genes. Activated NRF2 enters the nucleus and binds to antioxidant response elements (ARE), initiating the transcription of a series of downstream protective genes, including:
   • Superoxide dismutase (SOD1, SOD2)Catalytic dismutation of superoxide anions into hydrogen peroxide and oxygen.
   • Catalase (CAT)Catalytic decomposition of hydrogen peroxide into water and oxygen.
   • Glutathione peroxidase 1 (GPX1)Reduce hydrogen peroxide and organic peroxides using glutathione.
   • Heme oxygenase 1 (HMOX1)Catalyze the degradation of heme, producing biliverdin, carbon monoxide, and ferrous ions with antioxidant and anti-inflammatory effects.
   • Quinone oxidoreductase 1 (NQO1)Catalytic detoxification of quinone compounds.

By upregulating the expression of these key antioxidant enzymes, 7-O-methylcatechol can significantly enhance the overall antioxidant capacity of cells, thereby resisting oxidative damage more persistently and effectively.

Other potential activities

Based on its antioxidant and anti-inflammatory potential, 7-O-methylprednisolone has also shown preliminary activity in other fields:

• anti-inflammatory activity Oxidative stress is closely related to inflammatory response. By inhibiting pro-inflammatory signaling pathways such as NF - κ B, 7-O-methylprednisolone may reduce the production of pro-inflammatory cytokines (such as TNF - α, IL-6, IL-1 β). In addition, its regulatory effect on matrix metalloproteinases (MMP1, MMP3) suggests that it may play a role in tissue remodeling and inflammation related diseases.
• Skin protective activity Tyrosinase (TYR) is a key rate limiting enzyme in melanin synthesis. Some flavonoids are effective tyrosinase inhibitors. The potential inhibitory effect of 7-O-methylcatechol on TYR makes it a candidate molecule for developing whitening or treating hyperpigmentated skin diseases such as melasma. At the same time, its antioxidant and inhibitory effects on the activity of MMPs (such as MMP1, collagenase) help protect skin collagen and resist UV induced photoaging.
• Neuroprotective activity Although its BBB penetration prediction is low, it may still enter the central nervous system in certain pathological conditions (such as blood-brain barrier damage). Its powerful antioxidant and anti-inflammatory abilities theoretically have protective potential against neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, but related in vivo research is not yet sufficient.

Mechanism of action and molecular targets

The pharmacological effects of 7-O-methylcatechol are the result of multi-target and multi pathway synergistic effects. The core mechanism revolves around regulating redox balance and inflammatory response.

Core mechanism: Activation of NRF2-ARE signaling pathway

This is the most critical mechanism by which 7-O-methylcatechol exerts antioxidant and cell protective effects. The specific process is as follows:
1. Perceived oxidative stress Under normal physiological conditions, NRF2 binds to its negative regulatory factor Kelch like ECH related protein 1 (KEAP1) and is degraded by ubiquitination.
2. Decorate KEAP1 7-O-methylthymol or its metabolites act as electrophilic molecules that can covalently modify key cysteine residues (such as Cys151, Cys273, Cys288) on KEAP1 protein. This modification changes the conformation of KEAP1, causing it to dissociate from NRF2.
3. NRF2 stability and nuclear translocation After dissociation, NRF2 is no longer degraded and can stabilize and accumulate. Subsequently, NRF2 translocates into the nucleus.
4. Initiate transcription In the nucleus, NRF2 forms heterodimers with small Maf proteins, recognizes and binds to the ARE sequence of the target gene promoter region, and initiates the transcription of a series of downstream protective genes, including SOD1, SOD2, CAT, GPX1, HMOX1, etc.

Regulation of other signaling pathways and targets

• Inhibition of NF - κ B pathway Oxidative stress and inflammatory signals are often amplified by activating the NF - κ B pathway. 7-O-methylcatechol may inhibit the activity of I κ B kinase (IKK), prevent the phosphorylation and degradation of I κ B, and thus "trap" NF - κ B (p65/p50) complexes in the cytoplasm, preventing them from entering the nucleus to initiate the transcription of pro-inflammatory genes (such as COX-2, iNOS, TNF - α).
• Regulating matrix metalloproteinases (MMPs)MMPs are important enzymes that degrade the extracellular matrix and play a crucial role in tissue remodeling, inflammation, and tumor invasion. 7-O-methylcatechol can inhibit the expression and activity of MMP1 (interstitial collagenase) and MMP3 (matrix metalloproteinase-1). The mechanism may involve inhibition of the MAPK (such as ERK, JNK, p38) signaling pathway, as well as upregulation of tissue metalloproteinase inhibitors (TIMPs) expression through activation of NRF2.
• Inhibition of Tyrosinase (TYR)The initial step of tyrosinase catalyzed melanin synthesis. 7-O-methylcatechol may inhibit its activity and reduce melanin production by chelating with copper ions in the active center of tyrosinase or competitively binding to substrate binding sites.

Target Network Analysis

From the provided target list (TYR, MMP1, NFE2L2, NRF2, SOD1, CAT, GPX1, HMOX1, MMP3, SOD2), it can be seen that the target network of 7-O-methylcatechol is highly concentrated in Antioxidant defense and Extracellular matrix remodeling Two functional modules. NFE2L2 (NRF2) is the core hub, and its downstream SOD1, SOD2, CAT, GPX1, and HMOX1 form a powerful antioxidant enzyme system. MMP1 and MMP3 represent their roles in tissue protection. TYR points to its potential applications in pigment metabolism. This multi-target synergistic mode of action may give it an advantage over single target drugs in dealing with complex diseases such as chronic inflammation and fibrosis driven by oxidative stress.

Evaluation of drug properties and pharmacokinetics

The conversion of natural products into clinical drugs must undergo strict pharmacological evaluation. Based on the aforementioned physicochemical parameters and preliminary pharmacological data, a preliminary evaluation of the pharmacological properties of 7-O-methylthymol can be conducted.

Pharmaceutical advantages

1. Good drug like properties Its molecular weight (302 Da) and LogP (2.30) both conform to the range of the Lipinski Five Rules (MW<500, LogP<5), indicating its fundamental potential as an oral drug. TPSA (96.22 Å ²) is also within an acceptable range, and compounds with TPSA<140 Å ² are generally considered to have good oral absorption potential.
2. Clear mechanism of action The core mechanism of action (activation of NRF2) is clear, and the target network is associated with multiple diseases, providing clear direction for subsequent indication selection.
3. Low risk of cardiac toxicity HERG inhibition prediction is negative, which is an important safety advantage as hERG channel inhibition is one of the main causes of drug-induced arrhythmias.
4. Structural modifiability There are still active functional groups such as 5-OH and 3 ', 4' - dihydroxy groups retained in the molecule, providing chemical space for further structural optimization (such as prodrug design, improving water solubility or targeting).

Drug Challenge

1. Poor water solubility LogS is only 0.2227, which belongs to insoluble compounds. Low water solubility is the main bottleneck limiting its oral absorption and bioavailability. Formulation techniques such as solid dispersions, nanoparticles, and cyclodextrin inclusion complexes are needed to improve their solubility and dissolution rate.
2. Metabolic stability issues Although 7-methylation blocks one metabolic site, there are still multiple easily metabolized groups in the molecule, especially the ortho dihydroxy group of the B ring. These phenolic hydroxyl groups are easily catalyzed by phase II metabolic enzymes (such as UDP glucuronosyltransferase UGTs and sulfotransferase SULTs) in vivo, leading to significant first pass effects and low oral bioavailability. In addition, the C-ring may also be oxidized by cytochrome P450 enzymes (CYPs).
3. Potential mutagenic risk The Ames test predicted a value of 0.6, indicating that it may have genetic toxicity. This requires strict in vitro and in vivo genetic toxicity testing (such as chromosome aberration testing, micronucleus testing) for validation and risk assessment. If the risk is confirmed, it will seriously hinder its development.
4. Low blood-brain barrier penetration For diseases that require functioning in the central nervous system, such as neurodegenerative diseases, low BBB penetration is a disadvantageous factor.

Pharmacokinetic characteristics (speculated)

Based on its physicochemical properties and studies of similar compounds, it can be inferred that the pharmacokinetic characteristics of 7-O-methylthymol are as follows:
* absorb Oral absorption may be poor due to its low water solubility and potential intestinal efflux (such as P-glycoprotein). After absorption, it may exist in the form of prototype and bound metabolites.
* distribution Due to its lipophilicity, it may be widely distributed in tissues, especially in organs with abundant blood flow such as the liver and kidneys. The plasma protein binding rate may be high.
* Metabolism The main metabolic pathways include: ① II combined reaction The 3 ', 4' - dihydroxy group of ring B and the 5-hydroxy group of ring A combine with glucuronic acid or sulfuric acid to form corresponding single or double complexes. ② Phase I oxidation reaction The C ring may be oxidized by CYP450 enzyme to open the ring, generating smaller phenolic acid metabolites. ③ O-demethylation The 7-methoxy group may be demethylated to regenerate coumarin.
* excretion Metabolites are mainly excreted through bile and urine.

Clinical application prospects and prospects

The unique pharmacological activity and relatively clear mechanism of 7-O-methylprednisolone provide possibilities for its application in multiple disease fields.

Potential application areas

1. Metabolic diseases Given that oxidative stress and chronic inflammation are the core pathological processes of insulin resistance, non-alcoholic fatty liver disease (NAFLD), and obesity, 7-O-methylprednisolone is expected to improve insulin sensitivity, alleviate liver steatosis, and inflammation by activating the NRF2 pathway. Its multi-target properties make it a potential candidate molecule for treating metabolic syndrome.
2. Skin Diseases and Beauty Its inhibitory activity on TYR can be used to develop new whitening agents for the treatment of pigmentation diseases such as melasma and freckles. At the same time, its antioxidant properties and inhibition of MMP1 activity make it potentially useful in combating skin photoaging and reducing wrinkles. Topical preparations may be an effective way to avoid the problem of low oral bioavailability.
3. cardiovascular disease Atherosclerosis is essentially a chronic inflammatory and oxidative stress disease. 7-O-methylsacrostachol may play a role in cardiovascular protection by inhibiting the oxidative damage of vascular endothelial cells, reducing the formation of foam cells, stabilizing plaque and other mechanisms.
4. Neurodegenerative diseases Although BBB penetration is low, it is still possible to deliver it into the brain through the design of prodrugs or nano delivery systems. In Alzheimer's disease models, its antioxidant and anti-inflammatory effects may help reduce beta amyloid (A β) - induced neurotoxicity and tau protein hyperphosphorylation.

Future research directions

In order to promote the clinical translation of 7-O-methylthymol, future research should focus on the following aspects:

1. In depth pharmacokinetic research Conduct pharmacokinetic experiments in vivo to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics in animals, especially to identify its main metabolites and their activities, and evaluate its oral bioavailability.
2. Toxicity assessment Systematic genetic toxicity, acute toxicity, and long-term toxicity studies must be conducted to clarify the safety window for the risks predicted by Ames test.
3. Structural Optimization and Medicinal Chemistry Systematic structural modification was carried out using 7-O-methyl coumarin as the lead compound. For example:
   • Improve water solubility Introducing hydrophilic groups such as phosphate and amino acids into molecules to produce prodrugs.
   • Improve metabolic stability Protect the adjacent phenolic hydroxyl group of the B ring (such as methylation or acetylation), or replace it with other more stable functional groups.
   • Improve targeting ability Design prodrugs with tissue or cell targeting functions.
4. Formulation development Develop new drug delivery systems, such as liposomes, nanoemulsions, phospholipid complexes, etc., to solve the problems of poor water solubility and low bioavailability.
5. In vivo efficacy verification Systematically evaluate its in vivo efficacy and elucidate its mechanism of action in various animal models of diseases, such as high-fat diet induced obese mice, UVB induced skin photoaging model, and DSS induced colitis model.

Conclusion

As a natural methylated derivative of coumarin, 7-O-methyl coumarin has shown remarkable research value in the field of antioxidant stress-related diseases due to its unique chemical structure and multi-target pharmacological activity, especially its strong antioxidant effect through activating the NRF2-ARE pathway. Although its poor water solubility, metabolic instability, and potential genetic toxicity risks pose major challenges on its pharmaceutical path, its clear mechanism, good drug like basis, and broad application prospects make it a natural product lead compound worthy of further exploration. Future research requires collaborative efforts in multiple areas such as medicinal chemistry, pharmacokinetics, toxicology, and new formulation technologies, with the potential to develop active molecules from this ancient plant into novel drugs for treating modern chronic diseases. The in-depth study of 7-O-methylcatechol not only helps to reveal the structure-activity relationship of naturally methylated flavonoids, but also provides a valuable example for discovering innovative drugs from traditional natural products.