Etoposide

Iupac Name：(5S,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one

CAS No.: 33419-42-0

Molecular Weight：588.562

Modify Date.: 2023-03-17 06:17

Introduction: It is used as anti-cancer drug mainly used for the treatment of small cell lung cancer, testicular cancer, malignant lymphoma and acute leukemia. It also has certain efficacy in treating neuroblastoma, rhabdomyosarcoma, ovarian cancer, non-small cell lung cancer, stomach cancer and breast cancer. View more+

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1. Names and Identifiers

1.1 Name: Etoposide
1.2 Synonyms: (-)-Etoposide, (5S,5aR,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl 4,6-O-[(1R)-ethylidene]-beta-D-glucopyranoside (5R,5aR,8aR,9S)-9-[[4,6-O-(1R)-Ethylidene-β-D-glucopyranosyl]oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one (5R,5aR,8aR,9S)-9-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-méthylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy}-5-(4-hydroxy-3,5-diméthoxyphényl)-5,8,8a,9-tétrahydrofuro[3',4':6,7]naphto[2,3-d][1,3]dioxol-6(5aH)-one (5R,5aR,8aR,9S)-9-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy}-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one (5S,5Ar,8aR,9R)-5-[[(4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one (5S,5aR,8aR,9R)-9-(4-Hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl 4,6-O-[(1R)-ethylidene]-Β-D-glucopyranoside (5S,5aR,8aR,9R)-9-(4-Hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl 4,6-O-[(1S)-ethylidene]-α-L-gulopyranoside (5S,5aR,8aR,9R)-9-(4-Hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl 4,6-O-ethylidene-β-D-glucopyranoside 4&lsquo-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-Β-D-glucopyranoside) 4″-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-Β-D-glucopyranoside) 4'-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-Β-D-glucopyranoside) 4'-Demethylepipodophyllotoxin ethylidene-Β-D-glucoside BMY-40481, Etoposide 4'-Dihydrogenphosphate, VP-16-213 EINECS 251-509-1 EPEG Etoposide (VP16) Etoposide [USAN:BAN:INN:JAN] Etoposide for system suitability Etoposide USP26 EtoposideETOPOSIDECAS:33419-42-0MES-012 Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 9-[(4,6-O-ethylidene-β-D-glucopyranosyl)oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-, (5R,5aR,8aR,9S)- Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 9-[[4,6-O-[(1R)-ethylidene]-Β-D-glucopyranosyl]oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-, (5R,5aR,8aR,9S)- Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 9-[[4,6-O-[(1S)-ethylidene]-α-L-gulopyranosyl]oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-, (5R,5aR,8aR,9S)- GAL4 [(1-147) + VP16 (411-490)] from Saccharomyces cerevisiae human herpesvirus 2 MFCD00869325 Vepeside VP-16-213

1.3 CAS No.: 33419-42-0

1.4 CID: 6419930

1.5 EINECS(EC#): 251-509-1

1.6 Molecular Formula: C29H32O13 (isomer)

1.7 Inchi: InChI=1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15?,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1

1.8 InChkey: VJJPUSNTGOMMGY-MRAJQDPKSA-N

1.9 Canonical Smiles: CC1OCC2C(O1)C(C(C(O2)OC3C4COC(=O)C4C(C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O

1.10 Isomers Smiles: C[C@@H]1OC[C@@H]2[C@@H](O1)[C@@H]([C@H]([C@@H](O2)O[C@H]3C4COC(=O)[C@@H]4[C@@H](C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O

2. Properties

2.1 Density: 1.55

2.1 Melting point: 236-251℃

2.1 Boiling point: 798.1 °C at 760 mmHg

2.1 Refractive index: -110.5 ° (C=0.6, CHCl3)

2.1 Flash Point: 263.6 °C

2.1 Precise Quality: 588.18400

2.1 PSA: 160.83000

2.1 logP: 1.33860

2.1 Solubility: DMSO: 30?mg/mL

2.2 Appearance: white powder

2.3 Storage: Ambient temperatures.

2.4 Chemical Properties: White or almost white, crystalline powder, slightly hygroscopic

2.5 Color/Form: Powder

2.6 pKa: 9.8(at 25℃)

2.7 Water Solubility: Insoluble in water.DMSO: 30?mg/mL

2.8 Spectral Properties: Specific optical rotation = -110.5 deg C @ 20 deg C/D ( c= 0.6 in chloroform).
UV max (abs methanol): 283 nm (epsilon 4245)

2.9 Stability: Stable under normal storage and usage conditions. Avoid elevated temperatures.

2.10 StorageTemp: 2-8°C

3. Use and Manufacturing

3.1 Methods of Manufacturing: A solution of 3 β (20 g, 26.01 mm01) in THF (150 ml) was added to a mixture of wet 5percent-Pd/C (2.5 g, 50percent water wet) in THF (50 ml) in a Buchi apparatus under nitrogen atmosphere. It was purged three times with nitrogen and hydrogen, and hydrogenated at 50 psi at room temperature. After 4 h, it was carefully depressurized and transferred out from the hydrogenation setup, which was washed with warm THF (55 °C, 2 x 200 ml). The rich reaction mixture was filtered on a Buchner funnel containing a 0.45 μm nylon membrane filter and celite-521. The celite cake was washed with the THF which had been used to clean the reactor. The filtrate was evaporated to .similar.50 ml of a light yellow solution. Water (300 ml) and 10percent NaHSO3 (3 ml) were added and stirred at room temperature for 30 min and at 3 °C for 30 min. The resulting colorless slurry was filtered, washed with cold water (2 x 25 ml) and dried to give etoposide (4, 14.83 g) in 96.8percent weight yield with purity of 100.0percent.A slurry of 3β (25 g, 32.5 mmol) in acetone (250 ml) and 5percent Pd/C (50percent water wet) was charged to a 1L hydrogenating vessel. Additional amount (250 ml) acetone was used to wash in the 3β and the catalyst. The resulting slurry was purged six times with nitrogen followed by hydrogen, and hydrogenated at 3 bar pressure and room temperature for an hour. On completion of the reaction, MeOH (250 ml) was added to solubilize the product, and the catalyst was removed by filtration. The reactor was rinsed with MeOH (250 ml), which was subsequently used in washing the spent catalyst. The combined filtrates were treated with NaHSO3 solution (1N, 7.5 ml) to remove any color and the solvent exchanged for MeOH by distillative exchange. The resultant MeOH slurry (325 ml) was heated to 65 °C, at which point water (500 m l) was added. The crystalline slurry was heated at 85 °C to form a clear solution, seeded with etoposide and cooled slowly to room temperature and then to 0 °C where it was held for an hour. The product was isolated by filtration and dried in vacuo to give etoposide (4, 17.6-17.99 g) in an average of 93.3percent weight yield with HPLC area percent greater than 99percent based on three runs.THF:CH3OH (1:1, 30 ml) was added to a mixture of 3β (2 g) and 4percent wet Pd/C catalyst in a Parr-shaker bottle. It was purged three times with hydrogen and hydrogenated at 50 psi. After 3.5 h at room temperature, the slurry was filtered through celite and was washed with warm methanol (56°C, 3 x 15 ml). The combined filtrates were evaporated to a solid to which water (25 ml) was added and evaporated to remove .similar.5 ml. The resulting aqueous slurry (.similar.25 ml) was stirred at room temperature for 15 min and at 20°C for 15 min, and filtered. The solid etoposide was washed with water (2 x 5 ml) and dried at 40°C to constant weight (1.42 g, 92.5percent yield). According to HPLC, it contained 99.7percent of 4.

3.2 Usage: It is used as anti-cancer drug mainly used for the treatment of small cell lung cancer, testicular cancer, malignant lymphoma and acute leukemia. It also has certain efficacy in treating neuroblastoma, rhabdomyosarcoma, ovarian cancer, non-small cell lung cancer, stomach cancer and breast cancer.

4. Safety and Handling

4.1 Symbol: GHS07;GHS08;

4.1 Hazard Codes: T

4.1 Signal Word: DANGER

4.1 Risk Statements: R45;R22

4.1 Safety Statements: S53;S45

4.1 Exposure Standards and Regulations: The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl etoposide and etoposide phosphate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

4.2 Packing Group: II

4.2 Octanol/Water Partition Coefficient: log Kow = 0.60

4.3 Other Preventative Measures: PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or biochem lab also apply to microbiological & cell-culture labs ... Special consideration should be given to route of admin. ... Safest method of administering volatile carcinogen is by injection of a soln. Admin by topical application, gavage, or intratracheal instillation should be performed under hood. If chem will be exhaled, animals should be kept under hood during this period. Inhalation exposure requires special equipment. ... Unless specifically required, routes of admin other than in the diet should be used. Mixing of carcinogen in diet should be carried out in sealed mixers under fume hood, from which the exhaust is fitted with an efficient particulate filter. Techniques for cleaning mixer & hood should be devised before expt begun. When mixing diets, special protective clothing &, possibly, respirators may be required. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with solid bottoms & sides & fitted with a filter top. When volatile carcinogens are given, filter tops should not be used. Cages which have been used to house animals that received carcinogens should be decontaminated. Cage-cleaning facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are decontaminated, & monitoring methods are necessary. Situations may exist in which the use of disposable cages should be recommended, depending on type & amt of carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres. ... Methods ... should ... where possible, be simple & sensitive. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops should be prohibited. Grossly contaminated cleaning materials should not be re-used ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/
SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

4.4 Hazard Class: 6.1(a)

4.4 Hazard Declaration: H302; H350

4.4 Cleanup Methods: PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

4.5 DisposalMethods: SRP: 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 quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.
PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/

4.6 RIDADR: 3249

4.6 Safety Profile: Poison by ingestion, intraperitoneal, intravenous, and subcutaneous routes. An experimental teratogen. Human systemic effects by ingestion and inhalation: agranulocytosis, aplastic anemia, and other changes in bone marrow. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits acrid smoke and fumes.

4.7 Caution Statement: P201-P280-P301 + P312 + P330-P308 + P313

4.7 Formulations/Preparations: Oral: Capsules, liquid-filled: 50 mg Etoposide Capsules, (Mylan), Vepesid (with parabens), (Bristol-Myers Squibb.
Parenteral: For injection concentrate, for IV infusion only: 20 mg/mL (100, 150, 200, 250, and 500 mg) Etoposide for Injection (with alcohol 30.5% v/v benzyl alcohol 3%), (Abbott, Bedford, GensiaSicor, SuperGen), Toposar, (Pfizer), VePesid, (with alcohol 30.5% v/v benzyl alcohol 3%), (Bristol-Myers Squibb); 20 mg/mL (1 g) pharmacy bulk package, Etoposide for Injection (with alcohol 30.5% and benzyl alcohol 3%), (Abbott, Bedford, GensiaSicor), VePesid (with alcohol 30.5% and benzyl alcohol 3%), (Bristol-Myers Squibb).
Etoposide Phosphate: Parenteral: For injection: 500 mg (of etoposide) pharmacy bulk package, Etopophos, (Bristol-Myers Squibb); 1 g (of etoposide ) pharmacy bulk package, Etopophos, (Bristol-Myers Squibb). For Injection, for IV infusion: 100 mg (of etoposide),Etopophos, (Bristol-Myers Squibb). /Etoposide phosphate/
Trade names for etoposide include Abiposid, Cehaposid, Celltop, Citodox, Eposin, Etocris, Etomedac, Etopol, Etoposid Ebewe, Etoposid Pharmacia Upjohn, Etoposid Austropharm, Etoposida Filaxis, Etoposid, Etoposide Dakota, Etoposide Injection, Etoposide P&U, Etoposide Pierre Fabre, Etoposido Asofarma, Etoposido Dakota Farma, Etoposido Farmitalia, Etosid Euvaxon, Exitop, Kebedil, Labimion, Lastet, Optasid, Toposar, VePesid and V?p?side-Sandoz.

4.8 WGK Germany: 3

4.8 RTECS: KC0190000

4.8 Safety: Hazard Codes of Etoposido (CAS NO.33419-42-0):?T,Xi
Risk Statements: 45-22-36/37/38
R45:May cause cancer.?
R22:Harmful if swallowed.?
R36/37/38:Irritating to eyes, respiratory system and skin.
Safety Statements: 53-45-36/37-26
S53:Avoid exposure - obtain special instructions before use.?
S45:In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)?
S36/37:Wear suitable protective clothing and gloves.?
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
RIDADR: 3249
WGK Germany: 3
RTECS: KC0190000
HazardClass: 6.1(a)
PackingGroup: II

4.9 Specification: ? Etoposido ,?its cas register number is 33419-42-0. It also can be called?(-)-Etoposide 4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside) ; 4'-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) ; 4'-O-Demethyl-1-O-(4,6-O-ethylidene-beta-D-glucopyranosyl)epipodophyllotoxin ; 4-Demethylepipodophyllotoxin beta-D-ethylideneglucoside ;9-((4,6-O-Ethylidene-beta-D-glucopyranosyl)oxy)-5,8,8a,9-
tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-furo(3',4':6,7)naphtho(2,3-d)-1,3-dioxol-6(5aH)-one, (5R-(5alpha,5abeta,8aalpha,9beta(R*)))- ; 9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4- hydroxy-3,4-dimethyloxyphenyl)furo (3',4'':6,7) naptho-(2,3-d)-1,3-dioxol-6 (5aH)-one ; CCRIS 2392 ; Epipodophyllotoxin VP-16213 ; Epipodophyllotoxin, 4'-demethyl-, 9-(4,6-O-ethylidene-beta-D-glucopyranoside) ; Epipodophyllotoxin-beta-D-ethyliden-glucoside, 4'-demethyl- ; Etopophos (phosphate salt) ; Etoposide ; Etoposidum ; Lastet ; Toposar ; UNII-6PLQ3CP4P3 ; VePesid ; Vepesid J ; Zuyeyidal trans-Etoposide ;?EPE . Etoposido (CAS NO.33419-42-0) is a?white crystalline powder.

4.10 Toxicity: LD50 oral in rabbit: 147mg/kg

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

Carcinogenicity, Category 1B

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Danger
Hazard statement(s)	H302 Harmful if swallowed H350 May cause cancer
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read and understood. P280 Wear protective gloves/protective clothing/eye protection/face protection.
Response	P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/\u2026if you feel unwell. P330 Rinse mouth. P308+P313 IF exposed or concerned: Get medical advice/ attention.
Storage	P405 Store locked up.
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

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6. NMR Spectrum

Predict 1H proton NMR

7. Synthesis Route

33419-42-0Total: 14 Synthesis Route

477-47-4 26 Suppliers

33419-42-0 293 Suppliers

Literatures:
Chemistry Letters, , p. 799 - 802
Yield: null

2280-44-6 3 Suppliers

33419-42-0 293 Suppliers

Literatures:
Chemistry Letters, , p. 799 - 802
Yield: null

3947-62-4 23 Suppliers

33419-42-0 293 Suppliers

Literatures:
Tetrahedron Letters, , vol. 33, # 33 p. 4831 - 4834
Yield: null

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8. Precursor and Product

precursor:

477-47-4

270928-23-9

92206-84-3

105-57-7

534-15-6

2280-44-6

3947-62-4

23363-33-9

270071-30-2

134659-25-9

23363-35-1

16477-16-0

92206-82-1

217475-21-3

6559-91-7

23363-34-0

View all

product :

23363-35-1

138261-30-0

9. Other Information

9.0 Merck: 14,3886

9.1 Pharmacological effects: The chemical name of etoposide is 9-(4, 6-O-ethylidene-β-D-glucopyranoside)-4'-demethyl-epipodophyllotoxin. It is an off-white crystalline powder and is odorless. Upon being exposed to light, heat, its color is easy to change. It is also hydroscopic. It is almost insoluble in water, slight soluble in methanol, dimethyl sulfoxide and also ethanol.
Etoposide is the newly semi-synthetic derivative of epipodophyllotoxin and belongs to mitotic inhibitors which can make the cells be stalled in the mid-mitosis stage. It is a cell cycle specific anticancer drug. This product can act on the DNA topoisomerase II (Topo II), to form a "Drug-enzyme-DNA" complex, preventing Topo II from participating in DNA repair, resulting in the stallation of DNA replication, thereby inhibiting the proliferation of tumor cell(IC 50 = 59.2 μ M). It mainly takes effects on S phase, G2 phase cells, and caused cell arrest in the G2 phase. The experimental study has found that the complex can be reversed with the elimination of drug. In that case, Top II will become free again so the damaged DNA get repair again, reducing its anti-tumor effect. Therefore, extending the treatment time can enhance the anti-tumor activity. It is mainly used for the treatment of small cell lung cancer, malignant lymphoma, malignant germ cell tumors, and leukemia and also has certain efficacy on treating neuroblastoma, rhabdomyosarcoma, ovarian cancer, non-small cell lung cancer, stomach cancer and esophageal cancer.
This product has a bioavailability of 48% (25% to 74%) after oral administration. The plasma concentration can reach peak at 0.5 to 4 hours after taking this drug. After intravenous injection of this product, the plasma concentration of this drug exhibits biphasic elimination with the half-life of α phase being (1.4 ± 0.4) h and half-life of β phase being (5.7 ± 1.8) hours. The plasma protein binding rate is 74% to 90% with the highest concentration being found in intestine, liver, and kidney while the drug concentration in the cerebrospinal liquid is only 2% to 10% of that in the blood. It is primarily subject to renal excretion with 45% being excreted in the urine at 72 hours after the administration wherein prototype accounts for two-thirds and metabolites account for 15%. 1.5% to 16% of the drug is excreted through from faeces via the bile.

9.2 Side effects: 1. Over-rapid intravenous infusion rate (less than 30 minutes for the first time of administration) may cause rash, chills, fever, bronchospasm, dyspnea and other allergic reactions.
2. The drug can cause obvious myelosuppression reaction including anemia, leukopenia and thrombocytopenia. This frequently occurs in 7 to 14 days after treatment and can recover after 20 days of stopping administration. Severe neutropenia is the dose-limiting toxicity of the drug.
3. There may be loss of appetite, nausea, vomiting, stomatitis, diarrhea, abdominal pain and constipation. Liver toxicity is rare and may be accompanied with increased level of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and bilirubin.
4. There may be occasional elevated level of blood urea nitrogen.
5. There may be dizziness, fatigue and tiredness with occasional numbness, headaches and so on; there may be heart palpitations, ECG changes, hypotension; interstitial pneumonia may also occur; hair loss is also common.

Figure 1 the structural formula of etoposide

9.3 Contraindications: 1. Patients of significantly lower amount of white blood cells and platelets should be disabled.
2. Patients of heart, liver and kidney dysfunction should be disabled.
3. Pregnant women and lactating women should be disabled.
4. Patients allergic to this drug should be disabled.

9.4 Uses: It is used as anti-cancer drug mainly used for the treatment of small cell lung cancer, testicular cancer, malignant lymphoma and acute leukemia. It also has certain efficacy in treating neuroblastoma, rhabdomyosarcoma, ovarian cancer, non-small cell lung cancer, stomach cancer and breast cancer.

9.5 Usage and Dosage: 1. Oral: single-administration; daily: 60~100mg /m2; continuously apply for 10 days and repeat every 3 to 4 weeks. For combination chemotherapy, apply 50 mg/m2 per day and continue to take 3 or 5 days.
2. Intravenous infusion: Use sodium chloride injection for dilute this product of required amount (this drug is instable in 5% glucose injection and can form a fine precipitate). The concentration should not be more than 0.25 mg/ml with the intravenous infusion time being not less than 30 minutes.
Solid tumors: 60~100mg/m2 per day; continue for 3 to 5 days with repeating the medication every 3 to 4 weeks.
Leukemia: 60~100mg/m2 per day; apply for 5 consecutive days; repeat the medication at certain interval according to the blood condition.
Common pediatric dose: for intravenous infusion, administer based on volume/surface area 100~150mg/m2 for continuous 3 to 4 days.

9.6 Precautions: 1. This product is not suitable for intravenous injection and the intravenous infusion rate should not be too fast and should at least last for half an hour, otherwise it can easily lead to hypotension, laryngeal spasm and other allergic reactions.
2. Don’t choose chest, abdomen and intrathecal injection for administration.
3. During the medication period, the patients should be subject be regular investigation on the peripheral blood condition as well as liver and kidney function.
4. This product should be administrated immediately after dilution. If precipitate occurs, it should be strictly prohibited.
5. This product can cause reproductive toxicity and teratogenicity to animals and can be excreted through breast milk. FDA provided the pregnancy safety of this drug being classified as D class.
This information is edited by Xiongfeng Dai from .

9.7 Drug Interactions: 1. Because this product has significant bone marrow suppression effect and should be taken care of when be used in combination with other anticancer drugs.
2. This product can inhibit the body's immune defense mechanism, so that vaccination is not able to stimulate the body to produce antibodies.
3. Within 3 months after the end of chemotherapy, it is not recommended for applying the vaccine virus.
4. This product has a high binding rate to the plasma protein and therefore, the drug bound to plasma protein can affect the excretion of this product.

9.8 Description: Etoposide is a plant alkaloid and an inhibitor of topoisomerase II (IC₅₀ = 60.3 μM). It inhibits proliferation of a variety of adenocarcinoma cells (IC₅₀s = 0.005-12,200 μM) and human umbilical vein endothelial (HUVEC) cells (IC₅₀ = 0.249 μM). It reduces tumor growth in an Ma human embryonal carcinoma mouse xenograft model when administered at a dose of 25 mg/kg, an effect that is enhanced by concomitant administration of the immunosuppressant cyclosporin A (Item No. 12088). Etoposide also inhibits nuclear receptor coactivator 3 (IC₅₀ = 2.48 μM). Formulations containing etoposide have been used in combination therapy in the treatment of cancer.

9.9 Chemical Properties: White or almost white, crystalline powder, slightly hygroscopic

9.10 Originator: Etopos,Lemery,Mexico

9.11 Uses: Etoposide is used for germinogenic tumors, ovarian, stomach, and lung cancer, Hodgkin’s disease, and non-Hodgkin’s lymphoma for both monotherapy and in combination therapy.

9.12 Uses: An antitumur agent that complexes with topoisomerase II and DNA to enhance double-strand and single strand cleavage of DNA and reversible inhitit religation. Blocks the cell cycle in S-phase and G2-phase of the cell cycle. Induces apoptosis in nor

9.13 Uses: A DNA topoisomerase II inhibitor. Semi-synthetic derivative of podophyllotoxin, related structurally to Teniposide. Antineoplastic.

9.14 Uses: anticonvulsant

9.15 Indications: Etoposide (VePesid) is a semisynthetic derivative of podophyllotoxin that is produced in the roots of the American mandrake, or May apple. Unlike podophyllotoxin and vinca alkaloids, etoposide does not bind to microtubules. It forms a complex with the enzyme topoisomerase II, which results in a single-strand breakage of DNA. It is most lethal to cells in the S- and G2-phases of the cell cycle. Drug resistance to etoposide is thought to be caused by decreased cellular drug accumulation.
Etoposide is most useful against testicular and ovarian germ cell cancers, lymphomas, small cell lung cancers, and acute myelogenous and lymphoblastic leukemia.Toxicities include mild nausea, alopecia, allergic reaction, phlebitis at the injection site, and bone marrow toxicity.

9.16 Manufacturing Process: Preparation of 2,3-Di-O-dichloroacetyl-(4,6-O-ethylidene)-β-D-glucopyranose (hydrogenolysis)
An over-dried 100 mL three-necked round bottom flask fitted with a stir bar, low temperature thermometer, and H2 inlet was charged with 2,3-di-Oetoposide dichloroacetyl-1-O-benzyloxycarbonyl-(4,6-O-ethylidene)-β-D-glucopyranose (1.8 mmol), in acetone (15-30% concentration) and 10% palladium on activated carbon powder (0.2 mmol). The solution was stirred until uniform and then cooled to -10°C to 0°C. After the reaction was over the catalyst was filtered over sintered glass containing a plug of celite under reduced pressure. The sintered glass is washed trice with one times the total reaction volume of anhydrous acetone and the filtrates are pooled and then concentrated to dryness under reduced pressure at a temperature close to 30°C. The crude residue was dried under vacuum at ambient temperature and above compound was thus obtained as white foam in 98% yield with a melting point of 130°-132°C (from acetone).
Preparation of 4'-Demethyl-epi-podophyllotoxin-4-(2,3-di-O-dichloroacetyl- 4,6-O-ethylidene)-β-D-glucopyranoside
An oven-dried, three-neck 250 mL round bottom flask was fitted with a stir bar, low temperature thermometer, septa and argon inlet, was introduced with 4'-demethyl-epi-podophyllotoxin (1 mmol), dry molecular sieve (1/16 δ pellets) and anhydrous dichloromethane (20-50% concentration). 2-3-Di-Odichloroacetyl-( 4,6-O-ethylidene)-β-D-glucopyranose (1.7 mmol) in dichloromethane (10-20% concentration) was added via double-ended needle. The suspension was stirred until homogenous and then cooled to -40°C to - 60°C in an atmosphere of argon and in the absence of moisture. To the stirred suspension was added via a syringe, trimethylsilyl trifluoromethane sulfonate (2 mmol) over 30 minutes. The reaction was held at between -50°C and - 40°C for 30 minutes. The course of the coupling reaction was monitored by thin layer chromatography. The suspension was allowed to warm to about - 30°C and filtered through a short celite/basic alumina column, eluting twice with one times the total reaction volume of dichloromethane. The pooled filtrate was evaporated under reduced pressure to yield the crude intermediate product 4'-demethyl-epi-podophyllotoxin-4-(2,3-di-Odichloroacetyl- 4,6-O-ethylidene)-β-D-glucopyranose (yield 80%). This crude product is used directly in the next step without any purification. A sample was purified by the chromatraton for spectroscopic identification. The results are as follows: m.p.: 242°-243°C (from methanol).
Preparation of 4-Demethyl-epi-podophyllotoxin-4-(4,6-O-ethylidene)-β-Dglucopyranose (etoposide)
To 0.8 mmol of 4'-demethyl-epi-podophyllotoxin-4-(2,3-di-O-dichloroacetyl- 4,6-O-ethylidene)-β-D-glucopyranose in 10-25% concentration in methanol is added 1.5 mmol of zinc acetate dihydrate. The reaction mixture is refluxed with stirring under heating for 90 minutes. After completion of the reaction, the mixture is cooled and the volume reduced to one third by rotary evaporation under reduced pressure. Working up is effected by diluting the reaction solution with 100 mL dichloromethane and 100 mL of water. The aqueous phase was washed with 50 mL of dichloromethane. The combined dichloromethane phases was washed twice with 50 mL water, 15 mL of methanol was added to the first wash to prevent precipitation of etoposide. The organic phase was dried over anhydrous sodium sulphate, filtered and concentrated by evaporation under vacuum to an amorphous solid. This solid was re-crystallized from methanol/n-pentane at -4°C to 0°C, thus obtaining colorless amorphous powder of Etoposide (yield 68%), if the mother liquors are treated the yield will be higher). Melting point: 256°-258°C.
Preparation of Etoposide employing 2,3-di-O-dichloroacetyl-(4,6-Oethylidene)- β-D-glucopyranose and boron trifluoride etherate as catalyst
4'-Demethyl-epi-podophyllotoxin (1 mmol) and 2,3-di-O-dichloroacetyl-(4,6- O-ethylidene)-β-D-glucopyranose (2 mmol) were introduced into dry dichloromethane under anhydrous condition. When the temperature was stabilized to -20°C to -30°C, boron trifluoride etherate (1.5 mmol) was added slowly with stirring. Reaction was continued at this temperature and monitored by thin layer chromatography. After the completion of the reaction as evidenced by TLC, the solution was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the crude intermediate product 4'-demethyl-epi-podophyllotoxin-4-(2,3-di-Odichloroacetyl- 4,6-O-ethylidene)-β-D-glucopyranose. This crude product was then converted to etoposide by following the procedure as above described. The yield of final product etoposide was about 60%.

9.17 Brand name: Toposar(Sicor); Vepesid (Bristol-Myers Squibb).

9.18 Therapeutic Function: Antitumor, Antineoplastic

9.19 General Description: Etoposide is available in 50- and 100-mg capsules for oral useand in 100-mg vials for IV use. The agent is approved for usein testicular cancer and small cell lung cancer. It has alsobeen used in a wide variety of cancers including NSCLC,Hodgkin’s and non-Hodgkin’s disease, Kaposi sarcoma,acute lymphocytic leukemia, neuroblastoma, choriocarcinoma,and epithelial, ovarian, testicular, gastric, endometrial,and breast cancers. Etoposide is one of the few natural productderivatives that can be administered orally. When givenby this route, bioavailability is 50%. Administration by the IVroute is also utilized, and the drug is widely distributed whengiven by either route. The agent is highly protein bound(90%) primarily to albumin. Low albumin levels may lead toan increase in free drug and require a lowering of the dose.The drug does not penetrate the blood-brain barrier at normaldoses but does during high-dose therapy. Elimination occursprimarily in the urine with 30% to 40% of an IV dose appearingas unchanged drug. The elimination half-life is 5 to 10hours. Metabolism involves opening of the lactone ring togive the hydroxy acid as the major metabolite. Epimerizationoccurs at C-3 to give the cis-lactone, which may also undergohydrolysis to give the hydroxy acid. Glucuronidation and sulfationof the 4'-OH give products that are inactive. Activemetabolites are formed as a result of CYP3A4 mediated oxidative-O-demethylation of the 3'-methoxy group to give thecatechol followed by oxidation to give the quinone. The toxicitiesof etoposide include dose-limiting myelosuppression,produces nausea and vomiting in 30% to 40% of patients,which is more commonly seen when the drug is administeredorally. The agent also produces anorexia, alopecia, mucositis,and hypersensitivity reactions that may be caused by etoposideor Cremophor EL (polyoxyethylated castor oil), which isused as a vehicle for IV administration of the drug. Leukemia,especially acute myelogenous leukemia, has been associatedwith the drugs’ ability to produce strand breaks with resultanttranslocation of genetic material. The leukemias are generallyseen 5 to 8 years posttreatment and have been associated withtranslocation of several different genes resulting in breakpointsaround the mixed lineage leukemia (MLL) gene.Transcription and translation of this altered DNA giveschimeric proteins, which form partly from the translocatedgene and partly from the MLL gene. Exactly how thesechimeric proteins lead to leukemia is not known, but similaralterations are seen with other topoisomerase inhibitors.

9.20 Usage: Etoposide is used as a inhibits DNA synthesis and is very active against cells in the late S and G2 phases of the cell cycle. Etoposide was reported to be used to serum starve Saos-2 M5(p53-/-) cells which were transfected by electroporation with indicated expression plasmids for flag-E2F1 and myc-EBNA3C for selection of colony forming units, thus studying the blocking effect of EBV Nuclear Antigen 3C on E2F1 Mediated Apoptosis Induced by the DNA Damage Response.

9.21 Storage Conditions: A solution of 3 β (20 g, 26.01 mm01) in THF (150 ml) was added to a mixture of wet 5percent-Pd/C (2.5 g, 50percent water wet) in THF (50 ml) in a Buchi apparatus under nitrogen atmosphere. It was purged three times with nitrogen and hydrogen, and hydrogenated at 50 psi at room temperature. After 4 h, it was carefully depressurized and transferred out from the hydrogenation setup, which was washed with warm THF (55 °C, 2 x 200 ml). The rich reaction mixture was filtered on a Buchner funnel containing a 0.45 μm nylon membrane filter and celite-521. The celite cake was washed with the THF which had been used to clean the reactor. The filtrate was evaporated to .similar.50 ml of a light yellow solution. Water (300 ml) and 10percent NaHSO3 (3 ml) were added and stirred at room temperature for 30 min and at 3 °C for 30 min. The resulting colorless slurry was filtered, washed with cold water (2 x 25 ml) and dried to give etoposide (4, 14.83 g) in 96.8percent weight yield with purity of 100.0percent.A slurry of 3β (25 g, 32.5 mmol) in acetone (250 ml) and 5percent Pd/C (50percent water wet) was charged to a 1L hydrogenating vessel. Additional amount (250 ml) acetone was used to wash in the 3β and the catalyst. The resulting slurry was purged six times with nitrogen followed by hydrogen, and hydrogenated at 3 bar pressure and room temperature for an hour. On completion of the reaction, MeOH (250 ml) was added to solubilize the product, and the catalyst was removed by filtration. The reactor was rinsed with MeOH (250 ml), which was subsequently used in washing the spent catalyst. The combined filtrates were treated with NaHSO3 solution (1N, 7.5 ml) to remove any color and the solvent exchanged for MeOH by distillative exchange. The resultant MeOH slurry (325 ml) was heated to 65 °C, at which point water (500 m l) was added. The crystalline slurry was heated at 85 °C to form a clear solution, seeded with etoposide and cooled slowly to room temperature and then to 0 °C where it was held for an hour. The product was isolated by filtration and dried in vacuo to give etoposide (4, 17.6-17.99 g) in an average of 93.3percent weight yield with HPLC area percent greater than 99percent based on three runs.THF:CH3OH (1:1, 30 ml) was added to a mixture of 3β (2 g) and 4percent wet Pd/C catalyst in a Parr-shaker bottle. It was purged three times with hydrogen and hydrogenated at 50 psi. After 3.5 h at room temperature, the slurry was filtered through celite and was washed with warm methanol (56°C, 3 x 15 ml). The combined filtrates were evaporated to a solid to which water (25 ml) was added and evaporated to remove .similar.5 ml. The resulting aqueous slurry (.similar.25 ml) was stirred at room temperature for 15 min and at 20°C for 15 min, and filtered. The solid etoposide was washed with water (2 x 5 ml) and dried at 40°C to constant weight (1.42 g, 92.5percent yield). According to HPLC, it contained 99.7percent of 4.

9.22 Biochem/physiol Actions: Etoposide is an antitumor agent that complexes with topoisomerase II and DNA to enhance double-strand and single-strand cleavage of DNA and reversibly inhibit religation. Blocks the cell cycle in in S-phase and G2-phase of the cell cycle; induces apoptosis in normal and tumor cell lines; inhibits synthesis of the oncoprotein Mdm2 and induces apoptosis in tumor lines that overexpress Mdm2.

9.23 Clinical Use: Etoposide is utilized in the treatment of small cell lung cancer and in combination with other agents in refractory testicular cancer.

9.24 Safety Profile: Poison by ingestion, intraperitoneal, intravenous, and subcutaneous routes. An experimental teratogen. Human systemic effects by ingestion and inhalation: agranulocytosis, aplastic anemia, and other changes in bone marrow. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits acrid smoke and fumes.

9.25 Chemical Synthesis: Etoposide, [[5R-(5α,5aβ,8aα,9β)]-9-[4,6-O-ethylidene-β-D-glucopyranosyl) oxy]-] 5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3,4: 6,7]-naphtho[2,3- d]-1,3-dioxol-6(5aH)-one (30.4.5), is made from 4-desmethylepipodophyllotoxin (30.4.3), the phenolic group of which being previously protected by benzyl chloroformate, which makes 4-carbobenzyloxy-4-desmethylepipodophyllotoxin (30.4.3). Next, the hydroxyl group at position C9 is esterified with 4,6-O-ethylyden-2,3-di-O-acetyl-β-D-glucopyranose in the presence of boron trifluoride to make the corresponding glucopyranoside 30.4.4. Removing the acetyl group in the glucopyranosyl part of the molecule using zinc acetate in sodium methoxide, and also removing the benzyloxycarbonyl protection by hydrogenation using a palladium on carbon catalyst gives the desired etoposide (30.4.5).

9.26 Metabolism: The drug is more than 96% protein bound, undergoes biphasic elimination, and has a terminal half-life of 4 to 11 hours. Approximately 35 to 45% of a dose is eliminated via the kidneys, with less than 6% excreted in feces. The drug should be used with caution in patients with renal or liver disease.

9.27 References: Hande, K. R. "Etoposide: four decades of development of a topoisomerase II inhibitor." European Journal of Cancer34.10(1998):1514.
Noda, K, et al. "Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer." New England Journal of Medicine 346.2(2002):85-91.

10. Computational chemical data

Molecular Weight: 588.562g/mol
Molecular Formula: C₂₉H₃₂O₁₃
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 588.18429107
Monoisotopic Mass: 588.18429107
Complexity: 969
Rotatable Bond Count: 5
Hydrogen Bond Donor Count: 3
Hydrogen Bond Acceptor Count: 13
Topological Polar Surface Area: 161
Heavy Atom Count: 42
Defined Atom Stereocenter Count: 9
Undefined Atom Stereocenter Count: 1
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADcfB4PAAAAAAAAAAAAAAAAAAAASJAAAA0aMECAAAAAEjRQAAAGgAACAAADRSwmAMyDoAABgCIAiDSCAACCAAgIAAAiAEGiIgdNzKGMRqicCMlwBUPuAfK6PyOoAABCAAQQADAAAYQADCAAAAAAAAAAA==

11. Question & Answer

What is the etoposide' side effects? Apr 02 2021
Etoposide is a cancer medicine that interferes with the growth and spread of cancer cells in the body.Etoposide is used to treat small cell lung cancer. It is usually given in combination with other cancer medicines.Etoposide can lower blood cells that help your body fight infections and help your ...

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