303-47-9

Basic information

• Product Name: OCHRATOXIN A
• Synonyms: (R)-N-[(5-CHLORO-3,4-DIHYDRO-8-HYDROXY-3-METHYL-1-OXO-1H-2-BENZOPYRAN-7-YL)CARBONYL-L-PHENYLALANINE;OCHRATOXIN A, ASPERGILLUS OCHRACEUS;OCHRATOXIN A;N-[[(3R)-5-CHLORO-3,4-DIHYDRO-8-HYDROXY-3-METHYL-1-OXO-1H-2-BENZOPYRAN-7-YL]CARBONYL]-L-PHENYLALANINE;N-[(3R)-(5-CHLORO-8-HYDROXY-3-METHYL-1-OXO-7-ISOCHROMANYL)CARBONYL]-L-PHENYLALANINE;(-)-l;(-)-n-((5-chloro-8-hydroxy-3-methyl-1-oxo-7-isochromanyl)carbonyl)-3-phenyla;(r)-n-[(5-chloro-3,4-dihydro-8-hydroxy-3-methyl-1-oxo-1h-2-benzopyran-7-yl)car
• CAS NO: 303-47-9
• Molecular Formula: C₂₀H₁₈ClNO₆
• Molecular Weight: 403.81
• EINECS: 206-143-7
• Product Categories: Cell Signaling and Neuroscience;Mold;Toxins and Venoms;OBiotoxins;Alphabetic;Analytical Standards;Mycotoxins;Single component solutions;Calcium signaling;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Heterocycles, Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals;antibiotic
• Mol File: 303-47-9.mol
• Article Data: 5

Chemical Properties

• Melting Point: 169°C
• Boiling Point: 632.4 °C at 760 mmHg
• Flash Point: 2 °C
• Appearance: White to off-white/powder
• Density: 1.2459 (rough estimate)
• Vapor Pressure: 7.3E-17mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: 2-8°C
• Solubility: ethanol: soluble
• PKA: 3.29±0.10(Predicted)
• Merck: 13,6772
• BRN: 8169012
• CAS DataBase Reference: OCHRATOXIN A(CAS DataBase Reference)
• NIST Chemistry Reference: OCHRATOXIN A(303-47-9)
• EPA Substance Registry System: OCHRATOXIN A(303-47-9)

Safety Data

• Hazard Codes: T+,T,Xn,F
• Statements: 45-46-61-26/27/28-36-20/21/22-11-40-28-39/23/24/25-23/24/25-65-48/23/24/25-36/38
• Safety Statements: 53-22-36/37/39-45-36-26-16-36/37-28-62
• RIDADR: UN 3462 6.1/PG 2
• WGK Germany: 3
• RTECS: AY4375000
• F: 10
• HazardClass: 6.1(a)
• PackingGroup: I
• Hazardous Substances Data: 303-47-9(Hazardous Substances Data)

Usage

Description

OCHRATOXIN A is a chlorinated benzopyran coupled to phenylalanine, a phenylalanine derivative resulting from the formal condensation of the amino group of L-phenylalanine with the carboxy group of (3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-2-benzopyran-7-carboxylic acid. It is a white crystalline powder and is among the most widely occurring food-contaminating mycotoxins, produced by Aspergillus ochraceus, Aspergillus carbonarius, and Penicillium verrucosum. Ochratoxins are toxic metabolites known to be nephrotoxic, teratogenic, and possibly carcinogenic.

Uses

1. Used in Research and Development:
OCHRATOXIN A is used as a research tool for studying its effects on various biological processes and mechanisms. It helps in understanding its role in inducing DNA strand breaks, sister chromatid exchanges, DNA adduct formation, or reactive oxygen species. It also aids in investigating its specific inhibition of NK cell activity, its impact on the growth of transplantable tumor cells in mice, and its effects on apoptosis and cellular signaling pathways.
2. Used in Food Safety and Quality Control:
OCHRATOXIN A is used as a reference substance in the development and validation of analytical methods for detecting and quantifying mycotoxins in the food industry. This helps ensure food safety and quality by monitoring and controlling the presence of harmful contaminants.
3. Used in Environmental Monitoring:
OCHRATOXIN A is used as a marker for assessing the presence of mycotoxins in the environment, particularly in agricultural products and foodstuffs. This helps in understanding the extent of contamination and implementing appropriate control measures to minimize the risk to human and animal health.
4. Used in Pharmaceutical Industry:
OCHRATOXIN A is used as a starting material or intermediate in the synthesis of potential therapeutic agents targeting specific cellular pathways affected by the toxin. This can lead to the development of new drugs for treating conditions related to the toxin's mechanism of action.
5. Used in Regulatory Compliance:
OCHRATOXIN A is used in the establishment of regulatory limits and guidelines for mycotoxin contamination in the food and feed industry. This ensures that the levels of ochratoxin A in food products are kept within safe limits, protecting consumers from potential health risks.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

OCHRATOXIN A is incompatible with strong oxidizing agents, strong acids and strong bases. . OCHRATOXIN A is a carboxylic acid derivative. Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt.

Hazard

Hepatotoxic, nephrotoxic, extremely toxic; possible carcinogen.

Fire Hazard

Flash point data for OCHRATOXIN A are not available; however, OCHRATOXIN A is probably combustible.

Biological Activity

Mycotoxin that increases activity of the endoplasmic reticulum ATP-dependent calcium pump. Induces JNK activation and apoptosis in MDCK-C7 cells at nanomolar concentrations. Stimulates lipid peroxidation.

Safety Profile

Confirmed carcinogen with carcinogenic and neoplastigenic data. Poison by ingestion, intraperitoneal, intravenous, and subcutaneous routes. Experimental teratogenic and reproductive effects. Mutation data reported. When heated to decomposition it emits very toxic fumes of Cland NOx.

Potential Exposure

Ochratoxin A, a carboxylic acid derivative and a naturally occurring toxic mold (strain of Aspergillus ochraceus), occasionally in storage grains such as wheat and on field crops such as corn and oilseed (i.e., cottonseed), in ancient tombs, and decayed vegetation. Used as a laboratory chemical for research. Not currently produced in the United States.

Carcinogenicity

Ochratoxin A is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.

Shipping

UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required. UN3462 Toxins, extracted from living sources, solid, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Incompatibilities

Ochratoxin A is Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fire. Keep away from alkaline materials, strong bases, strong acids, oxoacids, and epoxides. Compounds of the carboxyl group R.COOH Compounds of the carboxyl group react with all bases, both inorganic and organic (i.e.,amines) releasing substantial heat, water, and a salt that may be harmful. Incompatible with arsenic compounds (releases hydrogen cyanide gas), diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides (releasing heat, toxic, and possibly flammable gases), thiosulfates and dithionites (releasing hydrogen sulfate and oxides of sulfur).

Waste Disposal

Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal. Under 40 CFR 261.5 small quantity generators of this waste may qualify for partial exclusion from hazardous waste regulations.

InChI:InChI=1/C20H18ClNO6/c1-10-7-12-14(21)9-13(17(23)16(12)20(27)28-10)18(24)22-15(19(25)26)8-11-5-3-2-4-6-11/h2-6,9-10,15,23H,7-8H2,1H3,(H,22,24)(H,25,26)/p-1/t10-,15+/m1/s1

Upstream product

• 19165-63-0 (R)-(-)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-(1H)-2-benzopyran-7-carboxylic acid 
• 1421840-11-0 (3R)-5-chloro-8-hydroxy-3-methyl-3,4-dihydro-1H-isochromen-1-one 
• 1421840-10-9 (3R)-5-chloro-8-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one 
• 16281-42-8 8-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one 
• 830-54-6 8-methoxy-3-methyl-1H-isochromen-1-one 
• 952023-80-2 ethyl 8-hydroxy-3-methyl-1-oxoisochroman-7-carboxylate 
• 16281-39-3 5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-(1H)-2-benzopyran-7-carboxylic acid 
• 54870-23-4 ethyl 5-chloro-8-hydroxy-3-methyl-1-oxoisochroman-7-carboxylate 
• 63-91-2 L-phenylalanine 
• 16874-17-2 L-phenylalanine tert-butyl ester 

Downstream Products

• 19165-63-0 (R)-(-)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-(1H)-2-benzopyran-7-carboxylic acid 
• 4825-86-9 N-{[(3R)-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-7-yl]-carbonyl}-L-phenylalanine 
• 205034-32-8 N-{[(3R)-5,8-dihydroxy-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-7-yl]carbonyl}-L-phenylalanine 
• 774539-74-1 C₃₀H₃₁N₆O₁₃P 
• 1353892-87-1 C₃₀H₃₄N₄O₁₂S 
• 481053-26-3 C₃₀H₃₄N₄O₁₃S 

Relevant articles and documents

Ruthenium-NHC-Diamine Catalyzed Enantioselective Hydrogenation of Isocoumarins

A novel and practical chiral ruthenium-NHC-diamine system is disclosed for the enantioselective hydrogenation of isocoumarins, which provides a new concept to apply (chiral) NHC ligands in asymmetric catalysis. A variety of optically active 3-substituted 3,4-dihydroisocoumarins were obtained in excellent enantioselectivities (up to 99% ee). Moreover, this methodology was utilized in the synthesis of O-methylmellein, mellein, and ochratoxin A.

Synthesis of analogues of ochratoxin A

Four analogues of ochratoxin A (OTA) differing for the aminoacidic moiety were synthesised using ochratoxin (OTα) as the starting material. The condensation reaction between protected amino acids and OT, carried out in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC?HCl) and N-hydroxybenzotriazole (HOBt) as coupling agents, followed by deprotection and PTLC purification afforded OTA alanine, leucine, serine and tryptophane analogues in satisfactory yields (33-47%, based on OT).

A new and expedient total synthesis of ochratoxin A and d 5-ochratoxin A

A new total synthesis of the mycotoxin ochratoxin A (OTA) is presented, in which it is prepared in 9% overall yield from commercially available substrates. The key step consists of the condensation reaction between protected L-phenylalanine and 5-chloro-8-hydroxy-3-methyl-1-oxoisochromane-7-carboxylic acid (ochratoxin α, OTα). The same strategy could be successfully applied to L-d5-phenylalanine, leading to the first total synthesis of d5-OTA, a molecular tracer for the detection and analytical quantification of the natural mycotoxin in food samples by means of stable isotope dilution assay (SIDA). Georg Thieme Verlag Stuttgart.