Paclitaxel
TAXOL · BACCATIN III · Abraxane · Paclitaxe · 5β,20-Epoxy-1,7β-dihydroxy-9-oxotax-11-ene-2α,4,10β,13α-tetrayl 4,10-diacetate 2-benzoate 13-[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoate] · [2aR-[2aα,4β,4aβ,6α,9α(αR*,βS*),11α,12α,12aα,12bα]]-β-(Benzoylamino)-α-hydroxy-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-ylesterbenzenepropanoicacid · 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-ylester, (αR, βS)- · αR-hydroxy-βS-(benzoylamino)-benzenepropanoic acid, (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester
Identifikatoren & physikalische Daten
| CAS No. | 33069-62-4 |
|---|---|
| Summenformel | C47H51NO14 |
| Durchschnittliche Molmasse | 853,9 g/mol |
| Monoisotopische Masse | 853,33095531 g/mol |
| SMILES | CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O |
| InChIKey | RCINICONZNJXQF-MZXODVADSA-N |
| PubChem CID | 36314 |
| ChEMBL | CHEMBL428647 |
| ChEBI | CHEBI:45863 |
| EC No. | 608-826-9 |
| DTXSID | DTXSID9023413 |
Chemische & physikalische Eigenschaften
| XLogP | 2,5 |
|---|---|
| Polarare Oberfläche (TPSA) | 221 |
| H-Brücken-Donoren | 4 |
| H-Brücken-Akzeptoren | 14 |
| Frei drehbare Bindungen | 14 |
| Schwere Atome | 62 |
| Formalladung | 0 |
| Komplexität | 1.790 |
| Stoffklassen | Other Uses -> Biochemical Research |
| Arzneimittel | Pharmaceuticals -> AntibioticsPharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | 34.5 |
| Color/Form | White to off-white crystalline powderNeedles from aqueous methanol |
| Löslichkeit | InsolubleInsoluble in water5.56e-03 g/Lmethanol: 50 mg/mL, clear, colorless0.3mg/L(37 ºC) |
| Human Drugs | Breast FeedingLactationMilk, HumanAntineoplastic Agents, PhytogenicAntimitotic AgentsTubulin ModulatorsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine |
| Schmelzpunkt | 415 to 421 °F (NTP, 1992)216-217 °C213-216 °C (decomposition)213 - 216 °C213 °C (dec.)(lit.) |
| Optical Rotation | Specific optical rotation: -49 deg at 20 °C/D (methanol)UV max absorption 2 (methanol): 227, 273, nm (E= 29,800,1700)(c = 1, MeOH) [a]20D = -53 +- 20 degrees |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH315 (87.5%): Causes skin irritation [Warning Skin corrosion/irritation]P203, P233, P260, P261, P264, P264+P265, P270, P271, P272, P273, P280, P284, P302+P352, P304+P340, P305+P354+P338, P317, P318, P319, P321, P332+P317, P333+P317, P342+P316, P362+P364, P403, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 256 reports by companies from 27 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Hazard Traits - Developmental ToxicityReproductive Toxicity |
| DOT-Kennzeichnung | Poison |
| Brandgefahren | Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992) |
| Gesundheitsgefahren | Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: |
| Gefahrenübersicht | An irritant that may cause serious eye injuryMay cause skin and respiratory sensitizationMay cause liver and kidney injury and bone depressionSuspected mutagen and of being toxic to fertility or the developing child[Sigma-Aldrich MSDS] |
| Reaktive Gruppe | Alcohols and Polyols |
| Special Reports | Chem & Eng News 70 (41): 30-2 (1992)A discussion concerning the development and synthesis of taxol, a new antitumor drug.Van Ingen G et alSudden Unexpected Death Due to Taxus Poisoning: A report of five cases, with review of the literature. Forensic Sci Int 56 (1): 81-7 (1992). The clinical and autopsy findings are summarized, the diagnostic aspects are discussed and the literature concerning Taxus is reviewed.Correia JJEffects of Antimitotic Agents on Tubulin Nucleotide Interactions. Pharmacol Ther 52 (2): 127-47 (1991). The interaction of antimitotic drugs with guanine nucleotides in the tubulin-microtubule system is reviewed. Taxol stoichiometrically induces microtubule formation and, in the presence of guanosine triphosphate, assembly associated guanosine triphosphate hydrolysis. |
Anwendungen & Verwendung
Beschreibung
Paclitaxel, a natural product isolated from the bark of the Pacific yew, is effective in treating refractory metastatic ovarian cancer. Unlike any other antineoplastic agents, paclitaxel appears to have several possible mechanisms of action, including an antimicrotubule action through the promotion of tubulin polymerization and stabilization of microtubules, thereby, halting mitosis and promoting cell death. The supply of paclitaxel is limited by its low natural abundance and currently it is being manufactured by a semi-synthetic route from deacetylbaccatin Ⅲ that is isolated from the needles of the yew tree. Recent completion of two total syntheses of taxol conquered the structural complexity of the title compound and may be useful in obtaining certain closely related analogs, some of which have been found to have antitumor activity. Paclitaxel has potential uses in the treatment of metastatic breast cancer, lung cancer, head and neck cancer, and malignant melanoma.
History
Paclitaxel, initially named taxol, is a naturally occurring diterpenoid compound extracted from the Pacific yew tree, Taxus brevifolia. Paclitaxel was discovered by National Cancer Institute (NCI) in 1960s. Scientists were conducting screenings of plant extracts in search of potential anticancer agents when they discovered the distinctive cytotoxic properties of paclitaxel against cancer cells. In October of 1995, China became the second country with formal production of paclitaxel and its injection in the world.Paclitaxel/Taxol is on the World Health Organization’s Model List of Essential Medicines, and was at one point the best-selling cancer drug ever manufactured, with annual sales of $1.6 billion in 2000.
Verwenden
Paclitaxel is an antineoplastic that used to treat patients with lung, ovarian, breast cancer, head and neck cancer, and advanc ed forms of Kaposi's sarcoma. Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It is also used in the study of structure and function of microtubles into tubulin.
Herstellung & Synthese
synthetische
The total synthesis of paclitaxel (Taxol) is described. Double Rubottom oxidation of the bis(silyl enol ether) derived from a tricarbocyclic diketone effectively installed a bridgehead olefin and C-5/C-13 hydroxy groups in a one-step operation. The novel Ag-promoted oxetane formation smoothly constructed the tetracyclic framework of paclitaxel.Total Synthesis of PaclitaxelThe biosynthesis of paclitaxel involves the condensation of the three isoprenyl diphosphate (IPP) units with dimethylallyl diphosphate (DMAPP). Plants are unique in producing IPP and DMAPP by both the mevalonic pathway (MVA) in the cytosol or via the methylerythritol phosphate (MEP) pathway in the plastids.Paclitaxel: biosynthesis, production and future prospects