Patupilone

Base Information

• Chemical Name: Patupilone
• CAS No.: 152044-54-7
• Deprecated CAS: 681125-91-7
• Molecular Formula: C27H41NO6S
• Molecular Weight: 507.692
• Hs Code.: 29419090
• European Community (EC) Number: 604-822-6
• NSC Number: 684363
• UNII: UEC0H0URSE
• DSSTox Substance ID: DTXSID4046862
• Nikkaji Number: J1.358.973I
• Wikidata: Q27093987
• NCI Thesaurus Code: C1623
• Metabolomics Workbench ID: 21313
• ChEMBL ID: CHEMBL94657
• Mol file: 152044-54-7.mol

Synonyms:4,17-Dioxabicyclo[14.1.0]heptadecane-5,9-dione,7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-,[1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-;(-)-Epothilone B;EPO 906;Epothilone B;

Chemical Property of Patupilone

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 95-97 °C
• Refractive Index: 1.532
• Boiling Point: 680.188 °C at 760 mmHg
• PKA: 13.57±0.70(Predicted)
• Flash Point: 365.165 °C
• PSA: 137.49000
• Density: 1.137 g/cm³
• LogP: 4.47750
• Storage Temp.: Store at -20°C
• Solubility.: Soluble in DMSO (up to 40 mg/ml) or in Ethanol (up to 35 mg/ml).
• XLogP3: 4.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 2
• Exact Mass: 507.26545920
• Heavy Atom Count: 35
• Complexity: 816

Purity/Quality:

99% ^*data from raw suppliers

Epothilone B ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1CCCC2(C(O2)CC(OC(=O)CC(C(C(=O)C(C1O)C)(C)C)O)C(=CC3=CSC(=N3)C)C)C
• Isomeric SMILES: C[C@H]1CCC[C@@]2([C@@H](O2)C[C@H](OC(=O)C[C@@H](C(C(=O)[C@@H]([C@H]1O)C)(C)C)O)/C(=C/C3=CSC(=N3)C)/C)C
• Recent ClinicalTrials: Study of Patupilone in Patients With Brain Metastasis From Non-small Cell Lung Cancer
• Recent EU Clinical Trials: CINATRA: Chromosomal Instability and Anti-Tubulin Response Assessment: A Phase II Study of Epothilone B in Metastatic Colon Carcinoma in patients with Microsatellite Instability or Chromosomal Instability
• Description: Epothilone B (152044-54-7) induces microtubule polymerization. Causes cell cycle arrest at the G2-M transition (EC50 = 32 nM for HeLa cells). Induces apoptosis. Cell permeable.
• Uses: Epothilones are polyketide natural products that inhibit cancer cells by a mechanism similar to paclitaxel, and also are effective against paclitaxel-resistant tumours. Epothilone B is what is known as a microtubule stabilizer. When a cell divides, the chromosomes that will end up in each cell are separated by thin filaments called microtubules. Normally these microtubules then break down as the cell division progresses. This class of cytotoxic chemo drugs prevents that break down and thus prevents cells from completing division. Epothilone B is a microtubule inhibitor isolated from the myxobacteria, Sorangium cellulosum. Like epothilone A, epothilone B acts by stabilising microtubule formation at the taxol binding site, and causes cell cycle arrest at the G2/M transition, leading to cytotoxicity. Epothilone B (Epo B) is a macrolide that causes the formation of bundles of intracellular microtubules in non-mitotic cells, induces the formation of hyperstable tubulin polymers, and arrests cell cycling in mitosis. It induces mitotic arrest at the G2-M transition in Hs578T and HeLa cells (IC50 = 3 and 32 nM, respectively) as well as in multidrug resistant KB3-1 and KBV-1 cells (IC50 = 16 and 92 nM, respectively). Epo B causes cell cycle arrest at nanomolar IC50 values in cell lines from ovarian, breast, lung, colon, prostate, and squamous cancer.

Technology Process of Patupilone

There total 338 articles about Patupilone 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: 98.0%

epothilone D (189453-10-9) → epothilone B (152044-54-7)

Guidance literature:

With 3,3-dimethyldioxirane; In dichloromethane; at -50 ℃;

DOI:10.1002/(SICI)1521-3773(19981016)37:19<2675::AID-ANIE2675>3.0.CO;2-O

Reference yield: 71.0%

(E)-9,10-dehydroepothilone B (595558-95-5) → epothilone B (152044-54-7)

Guidance literature:

With TrisNHNH₂; triethylamine; In 1,2-dichloro-ethane; at 50 ℃; for 6h;

DOI:10.1021/ja046992g

Reference yield: 69.0%

epothilone D (189453-10-9) → epothilone B (152044-54-7) + (1R,3S,7S,10R,11S,12S,16S)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione

Guidance literature:

With Oxone; 1,1,1-trifluoro-2-propanone; edetate disodium; sodium hydrogencarbonate; In water; acetonitrile; at 0 ℃;

DOI:10.1021/ja971110h

upstream raw materials:

epothilone D

(1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-16-iodomethyl-8,8,10,12-tetramethyl-3-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione

(1S,3S,7S,10R,11S,12S,16R)-7-(tert-Butyl-dimethyl-silanyloxy)-11-hydroxy-8,8,10,12,16-pentamethyl-3-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione

(E)-9,10-dehydroepothilone B

Downstream raw materials:

epothilone D

(4S,7R,8S,9S,13Z,16S,1'E)-4,8-di-tert-butyldimethylsilyloxy-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-1-oxa-13-cyclohexadecene-2,6-dione

(1S,3S,7S,10R,11S,12S,16S)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4-oxabicyclo[14.1.0]heptadecane-5,9-dione

Epothilone F

Refernces

Stereoselective syntheses of epothilones A and B via nitrile oxide cycloadditions and related studies

10.1021/jo015791h

The research describes a concise and stereocontrolled total synthesis of epothilone A and a formal synthesis of epothilone B, which are structurally unique polyketide macrolides with significant anticancer activity. The synthesis routes leverage nitrile oxide cycloadditions and a highly diastereoselective convergent aldol coupling, resulting in the expeditious construction of these complex molecules with complete stereocontrol. Key chemicals used in the process include isoxazolines, allylic alcohols, phosphonates, and various reagents for selective oxidations, reductions, and protection/deprotection steps. The study not only achieves the synthesis of epothilones A and B but also contributes to the advancement of novel methodologies for carbon-carbon bond formation and the development of scalable approaches to these important natural products.