4'-Demethylepipodophyllotoxin ethylidene-beta-D-glucoside

Base Information

• Chemical Name: 4'-Demethylepipodophyllotoxin ethylidene-beta-D-glucoside
• CAS No.: 33419-42-0
• Molecular Formula: C29H32O13
• Molecular Weight: 588.565
• Hs Code.: 29389090
• NSC Number: 141540
• Wikidata: Q27216064
• ChEMBL ID: CHEMBL16671
• Mol file: 33419-42-0.mol

Synonyms:alpha-D-Glucopyranosyl Isomer Etoposide;Celltop;Demethyl Epipodophyllotoxin Ethylidine Glucoside;Eposide;Eposin;Eto GRY;Eto-GRY;Etomedac;Etopos;Etoposide;Etoposide Pierre Fabre;Etoposide Teva;Etoposide, (5a alpha)-Isomer;Etoposide, (5a alpha,9 alpha)-Isomer;Etoposide, (5S)-Isomer;Etoposide, alpha D Glucopyranosyl Isomer;Etoposide, alpha-D-Glucopyranosyl Isomer;Etoposido Ferrer Farma;Exitop;Lastet;NSC 141540;NSC-141540;NSC141540;Onkoposid;Riboposid;Teva, Etoposide;Toposar;Vépéside Sandoz;Vépéside-Sandoz;Vepesid;VP 16;VP 16 213;VP 16-213;VP 16213;VP-16;VP16

Chemical Property of 4'-Demethylepipodophyllotoxin ethylidene-beta-D-glucoside

Chemical Property:

• Appearance/Colour: White crystalline powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 236-251 °C(lit.)
• Refractive Index: -110.5 ° (C=0.6, CHCl3)
• Boiling Point: 798.054 °C at 760 mmHg
• PKA: 9.8(at 25℃)
• Flash Point: 263.603 °C
• PSA: 160.83000
• Density: 1.55 g/cm³
• LogP: 1.33860
• Storage Temp.: Store at RT
• Solubility.: DMSO: 30?mg/mL
• Water Solubility.: Insoluble in water.
• XLogP3: 0.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 13
• Rotatable Bond Count: 5
• Exact Mass: 588.18429107
• Heavy Atom Count: 42
• Complexity: 969

Purity/Quality:

99% ^*data from raw suppliers

Etoposide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, Xi
• Hazard Codes: T:Toxic
• Statements: R45:; R22:
• Safety Statements: S53:; S45:

MSDS Files:

SDS file from LookChem

Useful:

• 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
• Isomeric SMILES: CC1OCC2C(O1)C(C(C(O2)O[C@H]3[C@H]4COC(=O)[C@@H]4[C@@H](C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O
• Recent ClinicalTrials: Natural Killer (NK) Cell Therapy Targeting CD33 in Acute Myeloid Leukemia
• Recent EU Clinical Trials: PHASE II STUDY OF TOTAL MARROW AND LYMPHOID IRRADIATION (TMLI) GIVEN IN COMBINATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE (VP-16) AS CONDITIONING FOR ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) IN PATIENTS WITH HIGH-RISK ACUTE LYMPHOCYTIC OR MYELOGENOUS LEUKEMIA
• 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. 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. 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 A DNA topoisomerase II inhibitor. Semi-synthetic derivative of podophyllotoxin, related structurally to Teniposide. Antineoplastic. anticonvulsant
• 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.
• 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 . 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.
• 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.
• Therapeutic Function: Antitumor, Antineoplastic
• Clinical Use: Etoposide is utilized in the treatment of small cell lung cancer and in combination with other agents in refractory testicular cancer.
• Drug interactions: Potentially hazardous interactions with other drugs Anticoagulants: possibly enhanced anticoagulant effect with coumarins. Antipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosis. Ciclosporin: 50% reduction in etoposide clearance.

Technology Process of 4'-Demethylepipodophyllotoxin ethylidene-beta-D-glucoside

There total 45 articles about 4'-Demethylepipodophyllotoxin ethylidene-beta-D-glucoside 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: 96.8%

2''-3''-di-O-benzyletoposide (217475-21-3) → etoposide (33419-42-0)

Guidance literature:

With hydrogen; palladium on activated charcoal; In tetrahydrofuran; at 20 ℃; for 4h; under 2585.81 Torr;

DOI:10.1021/ol006262n

Reference yield: 85.0%

Carbonic acid benzyl ester 4-[(5R,5aR,8aR,9S)-9-((2R,4aR,6R,7R,8S,8aR)-7,8-bis-benzyloxy-2-methyl-hexahydro-pyrano[3,2-d][1,3]dioxin-6-yloxy)-6-oxo-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxy-phenyl ester (270928-23-9) → etoposide (33419-42-0)

Guidance literature:

With hydrogen; trifluoroacetic acid; palladium on activated charcoal; In methanol; ethyl acetate; for 12h; under 2585.81 Torr;

DOI:10.1021/ol005732a

Reference yield: 68.0%

4-demethylepipodophyllotoxin-7'-O-β-D-glucopyranoside (23363-35-1) + 1,1-dimethoxyethane (534-15-6) → etoposide (33419-42-0)

Guidance literature:

With toluene-4-sulfonic acid; In nitromethane; at 25 ℃; for 2h;

DOI:10.1016/S0040-4039(00)61297-2

upstream raw materials:

4,6-O-ethylidene-D-glucopyranose

1-O-(trimethylsilyl)-4,6-O-ethylidene-2,3-di-O-(dichloroacetyl)-β-D-glucopyranose

4,6-O-ethylidene-1,2,3-tri-O-(dichloroacetyl)-α-D-glucopyranose

etoposide

Downstream raw materials:

(5R,6S,7R,8S)-8-((2R,4aR,6R,7R,8R,8aS)-7,8-Dihydroxy-2-methyl-hexahydro-pyrano[3,2-d][1,3]dioxin-6-yloxy)-5-(4-hydroxy-3,5-dimethoxy-phenyl)-7-hydroxymethyl-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxole-6-carboxylic acid hydrazide

(5R,6R,7R,8S)-8-((2R,4aR,6R,7R,8R,8aS)-7,8-Dihydroxy-2-methyl-hexahydro-pyrano[3,2-d][1,3]dioxin-6-yloxy)-5-(4-hydroxy-3,5-dimethoxy-phenyl)-7-hydroxymethyl-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxole-6-carboxylic acid hydrazide

2'-chloroetoposide

(2R,4aR,6R,7R,8R,8aS)-6-[(5S,6R,7R,8R)-8-(4-Hydroxy-3,5-dimethoxy-phenyl)-6,7-bis-hydroxymethyl-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxol-5-yloxy]-2-methyl-hexahydro-pyrano[3,2-d][1,3]dioxine-7,8-diol

Refernces

New topoisomerases inhibitors: Synthesis of rutaecarpine derivatives and their inhibitory activity against topoisomerases

10.1007/s12272-012-0504-1

This research aimed to synthesize rutaecarpine derivatives and evaluate their inhibitory activities against topoisomerase I and II, enzymes crucial in DNA replication and transcription. The study was driven by the potential of these alkaloids, isolated from Rutaceous plants, to serve as natural product-based cytotoxic agents. The researchers synthesized a series of rutaecarpine derivatives using methods such as Fischer indole synthesis, acetic anhydride-mediated condensation, and ozonolysis, involving chemicals like 2-amino-5-chlorobenzoic acid, piperidin-2-one, benzaldehyde, and phenylhydrazine-HCl. The conclusions drawn from the study were that among the tested compounds, 10-bromorutaecarpine and 3-chlororutaecarpine exhibited strong inhibitory activities against both topo I and II, with effects somewhat stronger than those of the reference drugs camptothecin (CPT) and etoposide. These findings suggest that these rutaecarpine derivatives could be potential candidates for further development as topoisomerase inhibitors for therapeutic applications.