Griseofulvin

Base Information

• Chemical Name: Griseofulvin
• CAS No.: 126-07-8
• Deprecated CAS: 3426-54-8,8027-03-0,11103-62-1,24659-79-8,8055-10-5
• Molecular Formula: C17H17ClO6
• Molecular Weight: 352.771
• Hs Code.: 29419090
• European Community (EC) Number: 204-767-4
• NSC Number: 755822
• UNII: 32HRV3E3D5
• DSSTox Substance ID: DTXSID8020674
• Nikkaji Number: J4.418K
• Wikipedia: Griseofulvin
• Wikidata: Q416096
• NCI Thesaurus Code: C65819
• RXCUI: 5021
• Metabolomics Workbench ID: 27937
• ChEMBL ID: CHEMBL562
• Mol file: 126-07-8.mol

Synonyms:Fulvicin U F;Fulvicin-U-F;FulvicinUF;Grifulvin V;Gris PEG;Gris-PEG;Grisactin;Grisefuline;Griseofulvin;GrisPEG

Chemical Property of Griseofulvin

Chemical Property:

• Appearance/Colour: crystalline solid
• Vapor Pressure: 3.11E-11mmHg at 25°C
• Melting Point: 218-220 °C(lit.)
• Refractive Index: 1.565
• Boiling Point: 570.4 °C at 760 mmHg
• Flash Point: 228 °C
• PSA: 71.06000
• Density: 1.38 g/cm³
• LogP: 2.81030
• Storage Temp.: −20°C
• Solubility.: Practically insoluble in water, freely soluble in dimethylformamide and in tetrachloroethane, slightly soluble in anhydrous ethanol and in methanol
• Water Solubility.: practically insoluble
• XLogP3: 2.2
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 352.0713660
• Heavy Atom Count: 24
• Complexity: 575

Purity/Quality:

Above 99% ^*data from raw suppliers

Griseofulvin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,Xn
• Hazard Codes: T,Xn
• Statements: 60-61-40-43-45
• Safety Statements: 53-22-36/37/39-45

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antifungal Agents
• Canonical SMILES: CC1CC(=O)C=C(C12C(=O)C3=C(O2)C(=C(C=C3OC)OC)Cl)OC
• Isomeric SMILES: C[C@@H]1CC(=O)C=C([C@]12C(=O)C3=C(O2)C(=C(C=C3OC)OC)Cl)OC
• Recent ClinicalTrials: Bioequivalence (BE) Study of Test Griseofulvin 500 Milligram (mg) Tablets Versus Reference and Dose Proportionality Study of Test Griseofulvin 250 mg and 500 mg Tablets Under Fed Conditions
• Indications: In medicine, this product is suitable for the treatment of a variety of ringworm, including tinea capitis, tinea barbae, body tinea, jock itch, foot tinea and onychomycosis. The various kinds of tinea mentioned are caused by various fungi including Trichophyton rubrum, Trichophyton tonsorans, Trichophyton mentagrophytes, Fingers Trichophyton, etc., and Microsporon audouini, Microsporon canis, Microsporon gypseum and Epidermophyton floccosum, etc. due. This product is not suitable for treatment in mild cases, localized infection cases and cases which can be treated with topical antifungal agents. Griseofulvin is not effective in treating the infections of a various kinds of fungi such as Candida, Histoplasma, Actinomyces, Sporothrix species, Blastomyces, Coccidioides, Nocardio and Cryptococcus species as well as treating tinea versicolor. In agriculture, this product is first introduced by Brian et al (1951) for control of plant diseases. According to previous studies, it can be used for prevention of melon (melon) vine blight, crack spread disease, watermelon blight, anthracnose, apple blossom rot, apple cold rot, apple rot, cucumber downy mildew , strawberry gray mold, gourds hanging blight, powdery mildew of roses, chrysanthemums powdery mildew, rot flower lettuce, early tomato blight, tulip fire blight and other fungal diseases. Griseofulvin (Fulvicin, Grifulvin V) has been used safely and effectively for decades for dermatophyte infections of scalp and nails and for more widespread skin eruptions. However, infections in certain sites (e.g.. toenails) respond poorly. The drug is generally well tolerated, even in the long-term courses necessary for nail disease. Griseofulvin (Gris-PEG, Grifulvin, Grisactin, Fulvicin) is an oral fungistatic agent used in the long-term treatment of dermatophyte infections caused by Epidermophyton, Microsporum, and Trichophyton spp. Produced by the mold Penicillium griseofulvin, this agent inhibits fungal growth by binding to the microtubules responsible for mitotic spindle formation, leading to defective cell wall development. Ineffective topically, griseofulvin is administered orally but has poor gastrointestinal absorption; absorption can be improved by microcrystalline processing of the drug and by taking the drug with fatty meals. Peak serum levels occur 4 hours after dosing. Griseofulvin is metabolized in the liver and has a half-life of 24 to 36 hours. The drug binds to keratin precursor cells and newly synthesized keratin in the stratum corneum of the skin, hair, and nails, stopping the progression of dermatophyte infection.
• Drug Interactions: 1. Combination of this product together with ethanol can cause tachycardia, sweating, flushing of the skin, etc., so avoid taking them at the same time. 2. Combination with anticoagulant drugs such as warfarin, and coumarin can enhance the hepatic metabolism and leaving the efficacy of anticoagulation being weakened; so it is necessary to adjust the dose by monitoring the prothrombin time at the same time. 3. Combination with primidone, and phenobarbital can decrease the antifungal effect of this product which may be due to that absorption of barbiturates may reduce the absorption of this drug as well as the increased rate of its inactivation due to the induction of hepatic enzyme which causes the decreased blood concentration; thus should avoid this kind of combination of drugs. 4. Combination of estrogen-class contraceptive with the product can reduce the effect of orally administrated contraceptives which may be due to that the product may strengthen the metabolism of contraceptive drugs in the live, causing its decreased blood concentration; thus should avoid using them simultaneously.
• Description: Griseofulvin (126-07-8) is an antifungal antimitotic agent. Induces apoptosis of human germ cell tumor cells via disruption of connexin 43/tubulin association concomitant with enhanced translocation of connexin 43 from the cytoplasm to the nucleus.1?Inhibits the growth of adrenocortical cancer cells?in vitro.2 Griseofulvin inhibits centrosome clustering, induces spindle multipolarity, mitotic arrest and cell death in multiple tumor cell lines but not in diploid fibroblasts and keratinocytes with normal centrosome content.3
• Uses: adrenegic blocker, Ca channel blocker, coronary vasodilator, antiarrhythmic antifungal, inhibits mitosis in metaphase Griseofulvin is a spirobenzofuran produced by a number of Penicillium species, first isolated in the 1930s by Raistrick's group. Griseofulvin is a selective antifungal agent used to treat skin infections in animals and humans. Griseofulvin acts by binding to fungal tubulin and inhibiting the mitotic spindle. Griseofulvin's ability to bind to keratin is considered an important aspect of the metabolite's access to dermatophytic fungi. More recently, griseofulvin has become an important phenotypic marker in Penicillium taxonomy. An antifungal and antiproliferative agent that affects microtubules. It is an antifungal drug. It is used both in animal and in humans, to treat rigworm infections of the skin and nails. It is derived from the mold Penicillium griseofulvum.Environmental contaminants; Food contaminants.
• Therapeutic Function: Antifungal
• Clinical Use: In the treatment of ringworm of the beard, scalp, and other skin surfaces, 4 to 6 weeks of therapy is often required. Therapy failure may be to the result of an incorrect diagnosis; superficial candidiasis, which may resemble a dermatophyte infection, does not respond to griseofulvin treatment. Onychomycosis responds very slowly to griseofulvin (1 year or more of treatment is commonly required) and cure rates are poor; itraconazole and terbinafine hydrochloride are more effective than griseofulvin for onychomycosis. Dermatophyte infections of hair, skin and nail
• Drug interactions: Potentially hazardous interactions with other drugs Anticoagulants: metabolism of coumarins accelerated (reduced anticoagulant effect). Ciclosporin: griseofulvin possibly reduces ciclosporin concentration (two reports of such an interaction in literature). Oestrogens and progestogens: metabolism of oral contraceptives accelerated (reduced contraceptive effect). Ulipristal: possibly reduced contraceptive effect - avoid.

Technology Process of Griseofulvin

There total 47 articles about Griseofulvin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

diazomethane (186581-53-3,908094-01-9,334-88-3) + 2'-hydroxygriseofulvin (136616-32-5) → griseofulvin (126-07-8)

Guidance literature:

In tetrahydrofuran; Ambient temperature;

DOI:10.1021/ja00022a075

Reference yield:

chloroglucinol dimethyl ether (18113-21-8) → griseofulvin (126-07-8)

Guidance literature:

Multi-step reaction with 12 steps

1: 93 percent / pyridine

2: 94 percent / AlCl₃ / chlorobenzene / 0.5 h / Heating

3: 73 percent / diisopropylazodicarboxylate, tributylphosphine

4: 78 percent / LHMDS / tetrahydrofuran / -78 °C

5: 95 percent / MsN₃, Et₃N

6: 62 percent / 5 mol percent of rhodium pivalate 2(piv)4> / benzene / 1 h / Heating

7: 1.) O₃, 2.) DMS / 1.) CH₂Cl₂, MeOH

8: tetrahydrofuran / Ambient temperature

9: 100 percent / TFA

10: 1.) diphenyl phosphorazidate, Et₃N, 2.) aq. HCl / 1.) toluene, reflux, 2.) reflux, 2 h

11: 49 percent / NaOMe / methanol / Ambient temperature

12: 95 percent / tetrahydrofuran / Ambient temperature

With pyridine; hydrogenchloride; aluminium trichloride; rhodium(II) pivalate; 2,3-dimercapto-succinic acid; tributylphosphine; di-isopropyl azodicarboxylate; diphenyl phosphoryl azide; sodium methylate; ozone; triethylamine; Methanesulfonyl azide; trifluoroacetic acid; lithium hexamethyldisilazane; In tetrahydrofuran; methanol; chlorobenzene; benzene;

DOI:10.1021/ja00022a075

Reference yield:

3'-chloro-2'-hydroxy-4',6'-dimethoxyacetophenone (81325-85-1) → griseofulvin (126-07-8)

Guidance literature:

Multi-step reaction with 10 steps

1: 73 percent / diisopropylazodicarboxylate, tributylphosphine

2: 78 percent / LHMDS / tetrahydrofuran / -78 °C

3: 95 percent / MsN₃, Et₃N

4: 62 percent / 5 mol percent of rhodium pivalate 2(piv)4> / benzene / 1 h / Heating

5: 1.) O₃, 2.) DMS / 1.) CH₂Cl₂, MeOH

6: tetrahydrofuran / Ambient temperature

7: 100 percent / TFA

8: 1.) diphenyl phosphorazidate, Et₃N, 2.) aq. HCl / 1.) toluene, reflux, 2.) reflux, 2 h

9: 49 percent / NaOMe / methanol / Ambient temperature

10: 95 percent / tetrahydrofuran / Ambient temperature

With hydrogenchloride; rhodium(II) pivalate; 2,3-dimercapto-succinic acid; tributylphosphine; di-isopropyl azodicarboxylate; diphenyl phosphoryl azide; sodium methylate; ozone; triethylamine; Methanesulfonyl azide; trifluoroacetic acid; lithium hexamethyldisilazane; In tetrahydrofuran; methanol; benzene;

DOI:10.1021/ja00022a075

upstream raw materials:

diazomethane

(2S,2'R)-7-chloro-4,6-dimethoxy-2'-methyl-3H-spiro[benzofuran-2,1'-cyclohexane]-3,4',6'-trione

methanol

sodium methylate

Downstream raw materials:

O-methylorcinol

3-chloro-4,6-dimethoxysalicylic acid

(+)-epigriseofulvin

(2S,6'R)-7-chloro-4,6,2'-trimethoxy-6'-methyl-spiro[benzofuran-2,1'-cyclohex-2'-ene]-3,4'-dione-4'-(2,4-dinitro-phenylhydrazone)

Refernces

• 1、 Oda,Sato. "Stereochemistry of hydrogenation of (-)-dehydrogriseofulvin to (+)-griseofulvin with a cell-free system of Streptomyces cinereocrocatus". . p. 1077 - 1082. Retrieved 1985.
• 2、 Pirrung,Brown,Rege,Laughton. "Total synthesis of (+)-griseofulvin". . p. 8561 - 8562. Retrieved 2007/10/02.
• 3、 Tomozane,Takeuchi,Choshi,Kishida,Yamato. "Syntheses and antifungal activities of dl-griseofulvin and its congeners. I". . p. 925 - 929. Retrieved 2007/10/02.