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HCID 10607Erstellt: 31. Oktober 2026

1,3,3a,4,9,9a-Hexahydro-9-hydroxy-6,7-(methylendioxy)-4-(3',4',5'-trimethoxyphenyl)benz[f]isobenzofuran-3-on

podofilox · PODOPHYLLIC ACID LACTONE · (-)-PODOPHYLLOTOXIN · condylox · Condyline · β-Arteether · (5R,5aR,8aR,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one · nsc24818

https://huagongshe.com/de/chemical/10607

Molekülstruktur von 1,3,3a,4,9,9a-Hexahydro-9-hydroxy-6,7-(methylendioxy)-4-(3',4',5'-trimethoxyphenyl)benz[f]isobenzofuran-3-on

Identifikatoren & physikalische Daten

CAS No.477-47-4
SummenformelC22H22O8
Durchschnittliche Molmasse414,4 g/mol
Monoisotopische Masse414,13146766 g/mol
SMILESCOc1cc([C@@H]2c3cc4c(cc3[C@H](O)[C@H]3COC(=O)[C@H]23)OCO4)cc(OC)c1OC
InChIKeyYJGVMLPVUAXIQN-XVVDYKMHSA-N
PubChem CID10607
ChEMBLCHEMBL61
ChEBICHEBI:50305
EC No.208-250-4
DTXSIDDTXSID3045645
Lokaler Name1,3,3a,4,9,9a-Hexahydro-9-hydroxy-6,7-(methylendioxy)-4-(3',4',5'-trimethoxyphenyl)benz[f]isobenzofuran-3-on

Chemische & physikalische Eigenschaften

XLogP2
Polarare Oberfläche (TPSA)92,7
H-Brücken-Donoren1
H-Brücken-Akzeptoren8
Frei drehbare Bindungen4
Schwere Atome30
Formalladung0
Komplexität629
LogP (Verteilungskoeffizient)1.5log Kow = 2.01
Color/FormSolvated crystals
Löslichkeit100Insoluble in ethyl ether, ligroinslightly soluble in watersoluble in acetone, benzenevery soluble in ethanol, chloroform.In water, 150 mg/L at 25 °C /Estimated/1.14e-01 g/LDMSO:15.0(Max Conc. mg/mL)36.2(Max Conc. mM)
Schmelzpunkt228114-118 °C183 °CMP: 114-118 °C (effervescence)228 °C183-184 °C (lit.)
Dampfdruck8.3X10-15 mm Hg at 25 °C /Estimated/
Optical RotationHygroscopic amorphos white flakes, mp = 152-154 °C. Specific optical rotation = -76.4 deg (c=0.576 in methanol)specific optical rotation = -117.0 deg (c=0.668 in pyridine) /Podophyllotoxin-beta-D-glucoside/Specific optical rotation = -132.7 deg @ 20 °C/D, chloroform, 2%
Henry-KonstanteHenry's Law constant = 3.8X10-18 atm-cu m/mol at 25 °C /Estimated/
Physical DescriptionLight-brown to greenish-yellow powderCommercial resin preparations contain 5-25% podophyllum. [INCHEM]Solid
Collision Cross Section198.37 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]189.74 Ų [M+H]+ [CCS Type: TW199.47 Ų [M+K]+ [CCS Type: TW187.85 Ų [M+H-H2O]+ [CCS Type: TW190.1 Ų [M+H-H2O]+ [CCS Type: TW189.6 Ų [M+H]+ [CCS Type: TW
Other Experimental PropertiesSeveral polymorphic modifications. After drying up: mp = 183.3-184.0 °C. Specific optical rotation = -132.7 deg @ 20 °C/D (chloroform). Solubility in water at 23 °C = 12- mg/L. Soluble in alcohol, chloroform, acetone, warm benzene, glacial acetic acid.MW: 414.40. Crystals from acetone. MP = 214 °C. Higher-melting modification from abs ethanol, mp 228 °C. Specific optical rotation = +9.4 deg (c=0.7 in chloroform). Solubility in water at 25 °C approx 100 mg/L. Fairly soluble in chloroform, hot ethanol, acetic acid, acetone, dilute causticless soluble in benzene ether, carbon tetrachloride, propylene glycol. /Picropodophyllin/Hydroxyl radical reaction rate constant = 2.2X10-10 cu cm/molecule-sec at 25 °C /Estimated/
Siedepunkt453.31°C (rough estimate)
Dichte1.2649 (rough estimate)
Brechungsindex1.4480 (estimate)
Lagerbedingungen2-8°C
pKa (Säurekonstante)13.26±0.40(Predicted)
AggregatzustandPowder
FarbeWhite to off-white
Merck13,7628
BRN99163
StabilitätVery Hygroscopic
InChIKeyYJGVMLPVUAXIQN-XVVDYKMHSA-N
SMILESCOc1cc(cc(OC)c1OC)[C@H]2C3C(COC3=O)[C@@H](O)c4cc5OCOc5cc24
LogP (Verteilungskoeffizient)2.010
CAS Datenbank518-28-5(CAS DataBase Reference)

Sicherheit & Vorschriften

GHS-EinstufungThis chemical does not meet GHS hazard criteria for 2.2% (1 of 46) of reports.DangerH301 (93.5%): Toxic if swallowed [Danger Acute toxicity, oral]H310 (95.7%): Fatal in contact with skin [Danger Acute toxicity, dermal]H315 (97.8%): Causes skin irritation [Warning Skin corrosion/irritation]H319 (97.8%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]H335 (95.7%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposureRespiratory tract irritation]P261, P262, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P316, P319, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 46 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Reported as not meeting GHS hazard criteria per 1 of 46 reports by companies.There are 7 notifications provided by 45 of 46 reports by companies with hazard statement code(s).Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.
Regulatorische InformationenChemical: Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 5,8,8a,9-tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-, [5R-(5.alpha.,5a.beta.,8a.alpha.,9.alpha.)]-
Weitere SicherheitsinformationenIMAP assessments - Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 5,8,8a,9-tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-, [5R-(5.alpha.,5a.beta.,8a.alpha.,9.alpha.)]-: Environment tier I assessmentIMAP assessments - Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 5,8,8a,9-tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-, [5R-(5.alpha.,5a.beta.,8a.alpha.,9.alpha.)]-: Human health tier I assessment
BrandpotenzialPodofilox topical gel is flammable and should be kept away from open flames.

Anwendungen & Verwendung

Beschreibung

Podophyllotoxin (2,3-butyl-4-aromatic naphthene) is isolated from guijiu(Podophyllum) . There are two species as the main source of podophyllotoxin, Podophyllum hexandrum Royle and Podophyllum peltatum .Although podophyllotoxin has significant antitumor and antiviral activities, it showed several toxicity and side effects. Podophyllotoxin derivatives, etoposide (VP-16-213), Etopophos, amino sugar etoposide (NK6l1), and teniposide (VM26), have been developed as anticancer drugs. They are used to treat small cell lung cancer, testicular cancer, acute leukemia, malignant lymphoma, etc. But podophyllotoxin derivatives are not free of toxicity. Besides the narrowing of the anticancer spectrum and low water solubility, these drugs could induce severe myelosuppression, gastrointestinal side effects, etc.Although the synthetic and biosynthetic pathways of podophyllotoxin have been elucidated, it is still the most effective, economic, and fast way to extract podophyllotoxin from the plant.

History

Podophyllotoxin was first found in the Podophyllum peltatum L.The first time to isolate podophyllotoxin from podophyllin was in 1880. In 1942, it was found that venereal warts could be effectively treated by application of podophyllin.Subsequently, podophyllotoxin was reported to inhibit the growth of the tumor through the inhibition of the microtubule formation. The chemical structure of podophyllotoxin was elucidated in 1951.In the 1960s, two main podophyllotoxin derivatives were synthesized, etoposide and teniposide (VM-26) . In 1983, etoposide was approved by FDA.Etoposide and teniposide are used in frontline cancer therapy against various cancer types, such as small cell lung cancer, testicular cancer, etc. In 1996, etoposide phosphate analog (Etopophos) was launched in America. Etopophos is the prodrug of etoposide and can be rapidly absorbed and completely converted to the parent compound invivo. In 1990, WHO recommended 0.5% podophyllotoxin as the first-line drug for the treatment of condyloma acuminatum. Podophyllotoxin creams and gels are nowadays widely used in clinical practice.

Verwenden

Podophyllotoxin is a non-alkaloid toxin lignan extracted from the roots and rhizomes of Podophyllum species. It binds to topoisomerase II during the late S and early G2 stage, blocking tubulin polymerization and, thus, inhibiting mitosis. In addition to being used as a cathartic, purgative, antiviral agent, vesicant, and antihelminthic, podophyllotoxin is the starting material for the semi-synthesis of the anti-cancer drugs etoposide , teniposide , and etopophos.

Gefahrenübersicht
The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [ChemIDplus]
FDA-AnforderungenThe Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl podofilox, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Hazard Classes and CategoriesAcute Tox. 3 (93.5%)Acute Tox. 2 (95.7%)Skin Irrit. 2 (97.8%)Eye Irrit. 2 (97.8%)STOT SE 3 (95.7%)
LagerbedingungenPodofilox topical gel and topical solution should be stored at 15-30 °C. These preparations should not be exposed to excessive heatfreezing should be avoided. ...
EntsorgungsverfahrenSRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations.
ExpositionspfadeTopical application of 0.05 mL of 0.5% podofilox solution to external genitalia did not result in detectable serum levels. Applications of 0.1 to 1.5 mL resulted in peak serum levels of 1 to 17 ng/mL one to two hours after application.
ToxizitätsübersichtIDENTIFICATION: Podophyllum is a dermatological medication. Origin of the substance: Dried resin from the roots and rhizomes of Podophyllum peltatum (Mandrake or May apple plant) the North American varietyactive ingredients are lignans including podophyllotoxins (20%), alpha-peltatin (10%) and beta-peltatin (5%). It is a light brown to greenish yellow solid powder soluble in water, alcohol, chloroform, acetone, warm benzene and glacial acetic acid. Indications: Wart or corn removal preparation. Description: Podophyllum resin has an antimitotic action and is used principally as a topical treatment for ano-genital warts (condylomata acuminata). Podophyllum resin has been used on external genital, perianal and intrameatal warts, but should not be used on cervical or urethral warts. Care must be taken to avoid application to healthy tissue. Podophyllum resin is also used in an ointment for plantar warts. Podophyllum resin has been used as a laxative, but when taken by mouth, it has a marked purging action and it is highly irritating to the intestinal mucosa and produces violent peristalsis. It has been superseded by less toxic laxatives. HUMAN EXPOSURE: Main risk and target organs: Podophyllum resin's major active constituent, podophyllotoxin, is a lipid soluble compound that readily crosses cell membranes. Podophyllotoxin and its derivatives are potent cytotoxic agents that inhibit cell mitosis and deoxyribonucleic acid (DNA) synthesis in a manner similar to that of colchicine. Cell division is arrested and other cellular processes are impaired, gradually resulting in the disruption of cells and destruction of the tissue. Topical podophyllum is easily absorbed systemically and can cross the placenta. Either local application or oral ingestion may produce multisystem toxic effects. Summary of clinical effects: Features of systemic toxicity include nausea and vomiting (which may be persistent), tachypnea, fever, stupor, coma, tachycardia, hypotension, paralyticEtoposide, a semisynthetic derivative of podofilox, induces DNA breakage through its inhibition of topoisomerase II. The drug is most active in the late S and early G2 phases of the cell cycle. Teniposide is an analog with very similar pharmacologic characteristics. Podofilox derivatives display binding activity to the enzyme topoisomerase II during the late S and early G2 stage. For instance, etoposide binds and stabilizes the temporary break caused by the enzyme, disrupts the reparation of the break through which the double-stranded DNA passes, and consequently stops DNA unwinding and replication. Mutants resistant to either podofilox, or to its topoisomerase II inhibitory derivatives such as etoposide (VP-16), have been described in Chinese hamster cells. The mutually exclusive cross-resistance patterns of these mutants provide a highly specific mean to distinguish the two kinds of podofilox derivatives. Mutant Chinese hamster cells resistant to podofilox are affected in a protein P1 that was later identified as the mammalian HSP60 or chaperonin protein. (Wikipedia)
Natural Pollution SourcesFound in the rhizomes of North American Podophyllum peltatum L., Podophyllaceae ... also in P. emodi ... in Juniperus virginiana L., Cupressaceae.
Human Toxicity Excerpts/HUMAN EXPOSURE STUDIES/ Toxicity reported following systemic administration of podofilox in investigational use for cancer treatment included: nausea, vomiting, fever, diarrhea, bone marrow depression, and oral ulcers. Following 5 to 10 daily intravenous doses of 0.5 to 1 mg/kg/day, significant hematologic toxicity occured but was reversible. Other toxicities occurred at lower doses. Toxicity reported following systemic administration of podophyllum resin included : nausea, vomiting, diarrhea, peripheral neuropathy, altered mental status, lethargy, coma , tachypnea, respiratory failure, leukocytosis, pancytosis, hematuria, renal failure, and seizures.
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Non-Human Toxicity Excerpts/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ There are published reports that, in mouse studies, crude podophyllin resin (containing podofilox) applied topically to the cervix produced changes resembling carcinoma in situ. These changes were revisable at five weeks after cessation of treatment. In one reported experiment, epidermal carcinoma of the vagina and cervix was found in 1 out of 18 mice after 120 applications of podophyllin (the drug was applied twice weekly over a 15-month period). /Podophyllin resin//LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Podofilox was embryotoxic in rats that were given daily intraperitoneal doses of 5 mg/kg of body weight (29.5 mg per square meter of body surface areacorresponding to 19 times the maximum human recommended dose). It was not teratogenic in rats that were given daily topical doses of 0.21 mg/kg of body weight (2.95 mg per square meter of body surface areacorresponding to two times the maximum human recommended dose for 13 days./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Podofilox did not impair fertility in two generations of rats given daily topical doses of 0.2 mg/kg of body weight (1.18 mg per square meter of body surface area) (corresponding to the recommended human daily dose) during gametogenesis, mating, gestation, parturition, and lactation./GENOTOXICITY/ Podofilox is not mutagenic according to the Ames plate reverse mutation assay (at concentrations up to 5 mg podofilox, with or without metabolic activation) and BALB/3T3 cells (at concentrations up to 0.008 ug/mL without metabolic activation and 12 ug/mL with activation). Chromosome damage occurs at higher doses25 mg/kg (75 mg per square meter of body surface area) of podofilox caused disruption and breakage of chromosomes in vivo in the mouse micronucleus assay.
Antidote and Emergency TreatmentTreatment of systemic toxicity or accidental ingestion is essentially supportive. To decrease absorption: Wash the skin free of any remaining drug. Supportive care: Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.
Non-Human Toxicity ValuesLD50 Rat iv 8.7 mg/kgLD50 Rat ip 15 mg/kg
F1-8-10
Wassergefährdungsklasse (WGK)3
UN-TransportnummerUN 3462 6.1/PG 2
Zollcode29189090
RTECS-Nr.LV2500000
R-Sätze (R)21-25-36/37/38-23/25-23/24/25
ToxizitätLD50 in rats (mg/kg): 8.7 i.v.15 i.p. (Phillips)
GefahrensymboleT
Sicherheitshinweise (S)36/37/39-45-26
Gefahrenklasse6.1(a)Acute Tox. 3 DermalAcute Tox. 3 InhalationAcute Tox. 3 OralEye Irrit. 2Skin Irrit. 2STOT SE 3
VerpackungsgruppeII
Lagerklasse6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials
Gefahrstoffdaten518-28-5(Hazardous Substances Data)