Isocoumarin (CAS 491-31-6) — 1H-2-Benzopyran-1-one Research Grade Supplier
High-purity isocoumarin — the parent scaffold of a >500-member natural product family with broad-spectrum bioactivity. A mechanism-based serine protease inhibitor pharmacophore, ERβ-selective ligand core (>1000-fold selectivity), and versatile heterocycle building block. 95-97% HPLC purity. C₉H₆O₂. MW 146.14. MP ~47°C.
Request a QuoteProduct Overview
Isocoumarin (CAS 491-31-6, molecular formula C₉H₆O₂, MW 146.14) — also known as 1H-2-benzopyran-1-one, 1H-isochromen-1-one, 3,4-benzo-2-pyrone, and isochromen-1-one — is the simplest member and parent scaffold of the isocoumarin natural product family, a class of >500 secondary metabolites isolated from plants, fungi, and bacteria with remarkably broad pharmacological activity. Structurally isomeric to coumarin, the critical difference is the carbonyl position: C1 in isocoumarin vs C2 in coumarin — a seemingly subtle rearrangement that has profound biological consequences. Isocoumarins function as mechanism-based (suicide) irreversible inhibitors of serine proteases (human leukocyte elastase, thrombin, factors XIa/XIIa, and other therapeutically relevant proteases) by acylating the active-site serine — a mode of action entirely absent in coumarins. Beyond protease inhibition, the isocoumarin scaffold delivers ERβ-selective estrogen receptor modulation (>1000-fold selectivity over ERα), α-glucosidase inhibition (up to 11-fold more potent than acarbose), aromatase inhibition (IC₅₀ 1.6 µM, 24-fold selective over CYP1A1), and broad-spectrum antifungal activity rivaling commercial fungicides. As a synthetic building block, the isocoumarin lactone undergoes Pd-catalyzed carbonylative cyclization, DIBAL-H reduction, and nucleophilic ring-opening with amines to access isoquinolinones, isochromenes, and other nitrogen-containing heterocycles. This compound is the starting point for systematic medicinal chemistry exploration of one of Nature’s most biologically privileged scaffolds.
UPOR Biotech is a specialty research chemical supplier providing Isocoumarin at 95-97% HPLC purity in research-grade quantities from 25mg evaluation samples to bulk 5g+ production scales. Our product is supplied with full analytical documentation — ¹H-NMR, HPLC purity, and GC-MS or LC-MS molecular ion confirmation — enabling direct integration into medicinal chemistry SAR libraries, natural product derivatization programs, and pharmaceutical intermediate synthesis. Custom synthesis, scale-up to multi-gram quantities, and OEM/private label manufacturing are available for drug discovery teams requiring this privileged scaffold. ISO 9001:2015 certified quality management system. Free 25mg evaluation sample available for qualified academic and industry research groups.
Isocoumarin vs Coumarin — Why the Carbonyl Position Determines Biological Mechanism
While isocoumarin and coumarin share the same atoms (C₉H₆O₂), the relocation of the carbonyl from C2 (coumarin) to C1 (isocoumarin) transforms the lactone from a passive ring system into an electrophilic warhead. In isocoumarin, the C1 carbonyl is adjacent to the aromatic ring, making it susceptible to nucleophilic attack by active-site serine residues — forming a stable acyl-enzyme intermediate that irreversibly inactivates the protease. Coumarin’s C2 carbonyl is conjugated into the α-pyrone ring and resists nucleophilic attack. This single-atom positional difference is why isocoumarins inhibit elastase, thrombin, and factors XIa/XIIa at nanomolar concentrations while coumarins are completely inactive against these targets. For medicinal chemistry programs targeting thrombosis, inflammation, or coagulation — where irreversible protease inhibition is the desired mechanism — isocoumarin is the correct scaffold; coumarin is not a substitutable analog.
Technical Specifications
| Property | Specification |
|---|---|
| Product Name | Isocoumarin — Research Grade |
| Common Name / Synonyms | Isocoumarin; 1H-2-Benzopyran-1-one; 1H-Isochromen-1-one; 3,4-Benzo-2-pyrone; Isochromen-1-one; 1H-2-Benzopyran-1-one |
| CAS Number | 491-31-6 |
| Molecular Formula | C₉H₆O₂ |
| Molecular Weight | 146.14 g/mol |
| SMILES | O=C1C=2C(C=CO1)=CC=CC2 |
| InChIKey | IQZZFVDIZRWADY-UHFFFAOYSA-N |
| Appearance | Colorless to pale yellow crystalline solid with sweet, floral odor |
| Melting Point | ~47°C |
| Boiling Point | ~262-286°C (estimated at 760 mmHg) |
| Density | ~1.248 g/cm³ |
| Flash Point | ~103.5°C |
| Refractive Index | ~1.594 |
| LogP | ~1.79-1.99 |
| Assay (HPLC) | ≥95% (standard); ≥97% (high-purity grade) |
| Key Structural Feature | Benzopyranone lactone with C1 carbonyl — electrophilic warhead for serine protease acylation; isomer of coumarin (C2 carbonyl) |
| Solubility | Soluble in ethanol, ether, DMF, DMSO, dichloromethane; limited solubility in water |
| Stability | Stable under inert atmosphere; protect from light and moisture. Lactone ring susceptible to basic hydrolysis and nucleophilic ring-opening. |
| Storage Conditions | 2-8°C, sealed under argon or nitrogen, protected from light and moisture |
| Heavy Metals | ≤20 ppm (as Pb) |
| Loss on Drying | ≤0.5% |
| Residue on Ignition | ≤0.1% |
| Grade | Research Grade (RUO) — not for human diagnostic or therapeutic use |
| Certifications | ISO 9001:2015; COA with ¹H-NMR, HPLC, GC-MS/LC-MS per lot |
| Packaging | 25mg / 100mg / 250mg / 1g / 5g — amber glass vials with PTFE-lined caps, argon-flushed |
| MOQ | 25mg (evaluation); bulk quantities 100mg-5g+ |
| Shelf Life | 24 months from date of manufacture under recommended storage conditions |
Key Benefits for Drug Discovery
Mechanism-Based Serine Protease Inhibition — Irreversible Mode of Action
The C1 carbonyl of the isocoumarin lactone acts as an electrophilic warhead that acylates active-site serine residues — forming a stable acyl-enzyme intermediate that permanently inactivates the protease. This irreversible mechanism is unique to isocoumarins (coumarins lack it entirely) and is the basis for developing potent, selective inhibitors of elastase, thrombin, and coagulation factors XIa/XIIa for thrombosis and inflammation.
Irreversible InhibitionERβ-Selective Scaffold — >1000-Fold Selectivity Over ERα
Isocoumarin derivatives display extraordinary estrogen receptor subtype selectivity — certain analogs achieve >1000-fold preference for ERβ over ERα. This enables development of selective estrogen receptor modulators (SERMs) that target ERβ-specific biology (neuroprotection, anti-inflammation, prostate cancer suppression) without ERα-mediated proliferative effects in breast and uterine tissue.
Selective SERM DesignNatural Product-Validated Pharmacophore — 500+ Bioactive Members
The isocoumarin scaffold is validated by Nature across 500+ secondary metabolites with demonstrated antimicrobial, anticancer, antioxidant, anti-inflammatory, and enzyme-inhibitory activities. Starting medicinal chemistry from a natural-product-validated core — rather than a purely synthetic scaffold — increases the probability of identifying drug-like leads with favorable ADME profiles.
Nature-ValidatedVersatile Heterocycle Precursor — One Scaffold to Multiple Chemotypes
Isocoumarin is a strategic branching point for heterocycle synthesis: Pd-catalyzed carbonylative cyclization with alkynes yields 3-substituted isocoumarins; nucleophilic ring-opening with amines yields isoquinolinones; DIBAL-H reduction yields isochromenes; acid-catalyzed rearrangement yields 2-indanones. One building block enables systematic SAR across five distinct chemotypes.
Synthetic VersatilityResearch Applications
Serine Protease Inhibitor Development
Irreversible inhibitors of human leukocyte elastase (COPD, emphysema), thrombin (thrombosis), and factors XIa/XIIa (anticoagulation). Isocoumarin acylates the catalytic serine — a mechanism coumarin cannot replicate.
ERβ-Selective SERM Lead Discovery
Isocoumarin core for developing >1000-fold ERβ-selective ligands — targeting neuroprotection, prostate cancer, and metabolic disease without ERα side effects. The C3 and C7 positions enable orthogonal SAR exploration.
Agricultural Antifungal Lead Optimization
Isocoumarin natural products (alternariethers, peniisocoumarins) match or exceed commercial fungicides like triadimefon. The parent scaffold enables systematic SAR for improved potency and crop selectivity.
α-Glucosidase Inhibition for Metabolic Disease
Dihydroisocoumarin thunberginol C is ~11-fold more potent than acarbose (IC₅₀ 94.76 vs 1036.2 µM). The parent isocoumarin scaffold enables exploration of simplified synthetic analogs with improved potency.
Aromatase Inhibitor Design — CYP Selectivity
Isocoumarins achieve aromatase IC₅₀ of 1.6 µM with 24-fold selectivity over CYP1A1 and no inhibition of CYP2C8/3A4 — indicating low drug-drug interaction potential. A key advantage over non-selective aromatase inhibitors.
Heterocycle Synthesis — Isoquinolinone & Isochromene Access
Building block for Pd-catalyzed cyclization to 3-substituted isocoumarins, amine ring-opening to isoquinolinones, and DIBAL-H reduction to isochromenes — five chemotypes from one precursor.
Frequently Asked Questions
Isocoumarin (CAS 491-31-6, 1H-2-benzopyran-1-one) is a heterocyclic lactone isomeric to coumarin — the carbonyl group is at position 1 (vs position 2 in coumarin) and the double bond is at C3=C4. This structural isomerism has profound biological consequences: isocoumarins act as mechanism-based irreversible inhibitors of serine proteases (elastase, thrombin, factors XIa/XIIa) by acylating the active-site serine — a property entirely absent in coumarins. Dihydroisocoumarin derivatives consistently show superior potency and selectivity over coumarins in enzyme inhibition assays. Substituting an isocoumarin with a coumarin analog typically results in loss of potency, altered selectivity, or complete change in mechanism of action. For serine protease drug discovery, isocoumarin is the correct scaffold; coumarin is not a substitutable analog.
Isocoumarin is the parent scaffold for a diverse family of natural products with broad-spectrum bioactivity: (1) Serine protease inhibition — mechanism-based irreversible inhibitors of human leukocyte elastase, thrombin, and coagulation factors XIa/XIIa; (2) Antifungal activity — alternariether A was more potent than the commercial fungicide triadimefon against Colletotrichum musae; (3) Anticancer — isocoumarin derivatives show IC₅₀ values of 0.34-4.0 µM against prostate (PC3), breast (MCF-7), lung (A549), and colon (HCT-116) cancer cell lines; (4) α-Glucosidase inhibition — thunberginol C is ~11-fold more potent than acarbose (IC₅₀ 94.76 vs 1036.2 µM) for metabolic disease applications; (5) ERβ selectivity — >1000-fold selectivity over ERα for targeted SERM development; (6) Aromatase inhibition — IC₅₀ 1.6 µM with 24-fold selectivity over CYP1A1. This breadth of validated bioactivity across multiple therapeutic areas makes isocoumarin one of Nature’s most versatile privileged scaffolds.
Isocoumarin is a colorless to pale yellow crystalline solid (mp ~47°C, bp ~262-286°C). Soluble in ethanol, ether, DMF, DMSO, and dichloromethane; limited water solubility. Key synthetic transformations: (1) Pd(PPh₃)₂Cl₂/CuI-catalyzed carbonylative cyclization with terminal alkynes in DMF/Et₃N yields 3-substituted isocoumarins; (2) DIBAL-H reduction to the lactol intermediate followed by acid-catalyzed methanolysis yields isochromene derivatives; (3) nucleophilic ring-opening with primary amines yields N-substituted isoquinolinones; (4) the lactone is susceptible to basic hydrolysis — avoid strongly basic conditions unless ring-opening is desired. Storage: 2-8°C under inert atmosphere (argon or nitrogen), protected from light and moisture. Standard laboratory PPE recommended. COA with ¹H-NMR, HPLC purity, and GC-MS/LC-MS data provided with every order.
Natural isocoumarins from fungal, plant, and bacterial sources provide privileged starting points validated by millions of years of evolutionary optimization — but are often limited by supply, structural complexity, and difficulty of systematic derivatization. Synthetic isocoumarin scaffolds — starting from the parent isocoumarin (CAS 491-31-6) — enable systematic SAR exploration with complete control over substitution pattern, regiochemistry, and stereochemistry. Key potency benchmarks: talaromarins A-F showed up to 32-fold greater antioxidant potency than Trolox (IC₅₀ 0.009-0.27 mM vs 0.29 mM); versicoumarin A showed IC₅₀ of 3.8-4.0 µM against A549 and MCF-7 cancer cells; isocoumarin-triazole hybrids achieved IC₅₀ of 0.34 µM against PC3 prostate cancer — demonstrating that synthetic derivatization can match or exceed natural product potency. By starting from the parent isocoumarin scaffold, medicinal chemistry teams can access these potent chemotypes through well-established synthetic transformations without relying on low-yield natural product isolation from fungal cultures or plant extracts.
UPOR Biotech provides: Certificate of Analysis (COA) with HPLC purity assay (≥95% or ≥97%, depending on grade ordered), ¹H-NMR spectrum with peak assignments, and GC-MS or LC-MS molecular ion confirmation; Material Safety Data Sheet (MSDS) with handling, storage, and disposal guidance; ISO 9001:2015 Certificate of Conformance. Full batch traceability with assigned batch numbers. For pharmaceutical development programs: Drug Master File (DMF) support, residual solvent analysis (per USP <467>), and elemental impurity testing (per ICH Q3D) available upon request. MOQ starts at 25mg for initial evaluation; bulk quantities (100mg, 1g, 5g, and larger) with competitive volume-based pricing. Free 25mg evaluation samples available for qualified academic and industry research groups. Contact our technical sales team at [email protected] with your purity, quantity, and documentation requirements — we respond to all inquiries within 24 hours.