Podofilox

Base Information

• Chemical Name: Podofilox
• CAS No.: 518-28-5
• Deprecated CAS: 11016-28-7,8050-60-0,8061-07-2,8063-20-5
• Molecular Formula: C22H22O8
• Molecular Weight: 414.412
• Hs Code.: 29189090
• European Community (EC) Number: 208-250-4
• NSC Number: 759591,24818
• UNII: L36H50F353
• DSSTox Substance ID: DTXSID3045645
• Nikkaji Number: J6.582J
• Wikipedia: Podophyllotoxin
• Wikidata: Q421193
• NCI Thesaurus Code: C29368
• RXCUI: 8463
• Pharos Ligand ID: TC48JX7ZBBD1
• Metabolomics Workbench ID: 43396
• ChEMBL ID: CHEMBL61
• Mol file: 518-28-5.mol

Synonyms:Condyline;Condylox;CPH86;Epipodophyllotoxin;Podocon-25;Podofilm;Podofilox;Podophyllotoxin;Podophyllotoxin, (5R-(5 alpha,5a alpha,8a alpha,9 alpha))-Isomer;Podophyllotoxin, (5R-(5 alpha,5a alpha,8a alpha,9 beta))-Isomer;Podophyllotoxin, (5R-(5 alpha,5a alpha,8a beta,9 alpha))-Isomer;Podophyllotoxin, (5R-(5 alpha,5a beta,8a alpha,9 beta))-Isomer;Wartec;Warticon

Chemical Property of Podofilox

Chemical Property:

• Appearance/Colour: off-white fine crystalline powder
• Vapor Pressure: 3.82E-15mmHg at 25°C
• Melting Point: 183-184 °C(lit.)
• Refractive Index: 1.605
• Boiling Point: 597.92 °C at 760 mmHg
• PKA: 13.26±0.40(Predicted)
• Flash Point: 210.181 °C
• PSA: 92.68000
• Density: 1.37 g/cm³
• LogP: 2.40920
• Storage Temp.: 2-8°C
• XLogP3: 2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 4
• Exact Mass: 414.13146766
• Heavy Atom Count: 30
• Complexity: 629

Purity/Quality:

98%, ^*data from raw suppliers

Podophyllotoxin, 98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 21-25-36/37/38-23/25-23/24/25
• Safety Statements: 36/37/39-45-26

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Chemical Classes: Other Uses -> Pharmaceuticals
• Canonical SMILES: COC1=CC(=CC(=C1OC)OC)C2C3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)O
• Isomeric SMILES: COC1=CC(=CC(=C1OC)OC)[C@H]2[C@@H]3[C@H](COC3=O)[C@H](C4=CC5=C(C=C24)OCO5)O
• Recent EU Clinical Trials: Human papillomavirus infection: a randomised controlled trial of Imiquimod cream (5%) versus Podophyllotoxin cream
• Description: 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.
• Physical properties: Appearance: white needle crystal powder. Solubility: freely soluble in chloroform, acetone, ethyl acetate, and benzene; soluble in ethanol and ethyl ether; and insoluble in water. Melting point: after drying the melting point is 183–184°C. Specific optical rotation: 132.7°C (chloroform).
• Uses: Skin treatment for genital warts caused by some types of HPVs. antineoplastic, inhibits microtubule assembly, and human DNA topoisomerase II; antimitotic agent 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.
• Indications: Podophyllotoxin (Podofilox) is available alone and as the main cytotoxic ingredient in podophyllin (25% podophyllum resin), a mixture of toxic chemicals derived from May apple plants. The active ingredients inhibit cell mitosis. The drugs are used to treat condylomata acuminata. The most common toxic effects are skin irritation and less commonly, ulceration. Systemic absorption of podophyllin can occur (especially if applied to large, inflamed areas or mucosal surfaces), with gastrointestinal, hematological, renal, and hepatotoxic effects. In addition, seizures and peripheral neuropathy have been reported.
• Clinical Use: Podophyllotoxin is a useful agent for the treatment of condyloma acuminatum . Podophyllotoxin and its derivatives are also widely used in the treatment of cancer, such as lymphomas and lung carcinoma. Because of the several toxicity of podophyllotoxin, for example, the irritation of skin and mucous membranes, combination therapies are used to treat condyloma acuminatum or cancer.

Technology Process of Podofilox

There total 190 articles about Podofilox 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: 81.0%

(1R,2R,3R,4R)-4-O-(2'-trimethylsilylethoxy)methylpodophyllotoxin (261158-30-9) → podofilox (518-28-5)

Guidance literature:

With ethanethiol; magnesium bromide; In diethyl ether; benzene; at 0 - 20 ℃; for 11h;

DOI:10.1021/jo991582+

Reference yield: 39.0%

→ podofilox (518-28-5)

Guidance literature:

Reference yield:

podophyllotoxone (477-48-5,477-49-6,55515-07-6,60660-51-7,64550-42-1,64937-82-2,86594-36-7,130322-38-2) → epipodophyllotoxin (4375-07-9) + podofilox (518-28-5)

Guidance literature:

With zinc(II) tetrahydroborate; In diethyl ether; benzene; for 3.5h; Product distribution; Ambient temperature; different reducing agents, solvents, reaction temperatures and times;

upstream raw materials:

podophyllotoxin-7′-O-β-D-glucopyranoside

diazomethane

4-demethylpodophyllotoxin

podophyllotoxinyl acetate

Downstream raw materials:

Succinylpodophyllotoxin

(5aR)-9t-(4-carboxy-butyryloxy)-5t-(3,4,5-trimethoxy-phenyl)-(5ar,8at)-5,8,8a,9-tetrahydro-5aH-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxol-6-one

(5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl acetate

podophyllotoxinyl acetate

Refernces

• 1、 Li, Jian,Zhang, Xiao,Renata, Hans. "Asymmetric Chemoenzymatic Synthesis of (?)-Podophyllotoxin and Related Aryltetralin Lignans". supporting information. p. 11657 - 11660. Retrieved 2019/08/02.
• 2、 Ting, Chi P.,Tschanen, Esther,Jang, Esther,Maimone, Thomas J.. "Total synthesis of podophyllotoxin and select analog designs via C–H activation". . p. 3299 - 3308. Retrieved 2019/05/15.