Combretastatin A4

Base Information

• Chemical Name: Combretastatin A4
• CAS No.: 117048-59-6
• Molecular Formula: C₁₈H₂₀O₅
• Molecular Weight: 316.354
• Hs Code.: 29095000
• European Community (EC) Number: 631-427-6
• NSC Number: 613729
• UNII: 16U6OP69RQ
• DSSTox Substance ID: DTXSID101025983
• Nikkaji Number: J424.288B
• Wikipedia: Combretastatin_A-4
• Wikidata: Q5150955
• NCI Thesaurus Code: C2711
• Pharos Ligand ID: H9SSQYFZL1HD
• Metabolomics Workbench ID: 143437
• ChEMBL ID: CHEMBL67
• Mol file: 117048-59-6.mol

Synonyms:1-(3,4,5-trimethoxyphenyl)-2-(3'-hydroxy-4'-methoxyphenyl)ethene;2-methoxy-5-((z)-2-(3,4,5-trimethoxyphenyl)vinyl)phenyl dihydrogen phosphate;3,4,5-trimethoxy-3'-hydroxy-4'-methoxystilbene;CA4DP;combretastatin A-4;combretastatin A-4 disodium phosphate;combretastatin A4;combretastatin A4 phosphate;CRC 87-09;CRC-98-09;deoxycombretastatin A-4;fosbretabulin;isocombretastatin A-4;NSC 817373;NSC-817373;phenol, 2-methoxy-5-((1z)-2-(3,4,5-trimethoxyphenyl)ethenyl)-,1-(dihydrogen phosphate);phenol, 2-methoxy-5-((z)-2-(3,4,5-trimethoxyphenyl)ethenyl)-, dihydrogen phosphate

Chemical Property of Combretastatin A4

Chemical Property:

• Appearance/Colour: crystalline powder
• Vapor Pressure: 3.09E-10mmHg at 25°C
• Melting Point: 84.5-85.5 °C
• Refractive Index: 1.607
• Boiling Point: 490.269 °C at 760 mmHg
• PKA: 9.65±0.10(Predicted)
• Flash Point: 250.306 °C
• PSA: 57.15000
• Density: 1.184 g/cm³
• LogP: 3.59700
• Storage Temp.: Desiccate at -20°C
• Solubility.: DMSO: >10mg/mL
• XLogP3: 3.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 316.13107373
• Heavy Atom Count: 23
• Complexity: 358

Purity/Quality:

99% ^*data from raw suppliers

Combretastatin A4 ^*data from reagent suppliers

Safty Information:

• Hazard Codes: T
• Statements: 23/24/25-41
• Safety Statements: 26-36/37-39-45

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: COC1=C(C=C(C=C1)C=CC2=CC(=C(C(=C2)OC)OC)OC)O
• Isomeric SMILES: COC1=C(C=C(C=C1)/C=C\C2=CC(=C(C(=C2)OC)OC)OC)O
• Description: Combrestatin A4 (CA4) is a potent inhibitor of tubulin polymerization and displays strong inhibitory activity on tumor cell growth. Combrestatin A4 was shown to inhibit tumor growth in several cell lines including IMR32 (neuroblastoma), Hs746T (gastric carcinoma), CFPAC-1 (pancreatic carcinoma), and MCF-7 (breast cancer) with IC50 values of 2.16, 5.20, 3.46, and 18.47 nM, respectively. CA4 inhibits tubulin polymerization with an IC50 value of 2.2 μM.
• Uses: Combretastatin is a small organic molecule found in the bark of the African bush willow tree Combretum caffrum. Combretastatin-A4 Prodrug Induces Mitotic Catastrophe in Chronic Lymphocytic Leukemia Cell Line Independent of Caspase Activation and Poly(ADP-ribose) Polymerase Cleavage. A potent cytotoxic agent which strongly inhibits the polymerization of tubulin by binding to the colchicine site. Combretastatin A4 has been used: as an anti-tubulin agent to determine the effects of isocitrate dehydrogenases (IDH1 and IDH2) proteins in G2/M phase to evaluate the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models as a microtubule inhibitor to study its effects on motility of Ascaris suum L3 larvae

Technology Process of Combretastatin A4

There total 135 articles about Combretastatin A4 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: 96.35%

C37H34O5 → combrestatin A4 (117048-62-1,117048-59-6)

Guidance literature:

With hydrogenchloride; In ethanol; water; at 20 ℃; for 3h;

Reference yield: 95.0%

2-(3-hydroxy-4-methoxyphenyl)-1-(3',4',5'-trimethoxyphenyl)ethyne (185698-55-9) → combrestatin A4 (117048-62-1,117048-59-6)

Guidance literature:

With ethanol; (NCP)IrHCl; tert-butylamine; at 75 ℃; for 24h; stereoselective reaction; Inert atmosphere; Sealed tube;

DOI:10.1021/jacs.1c01472

Reference yield: 92.0%

(Z)-5-(3-((2-methoxyethoxy)methoxy)-4-methoxystyryl)-1,2,3-trimethoxybenzene (1362101-30-1) → combrestatin A4 (117048-62-1,117048-59-6)

Guidance literature:

With hydrogenchloride; water; In tetrahydrofuran; at 20 ℃; for 15h;

DOI:10.1021/ol300276p

upstream raw materials:

(Z)-5-(3-tert-butyldimethylsilyloxy-4-methoxystyryl)-1,2,3-trimethoxybenzene

{2-Methoxy-5-[(Z)-2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-dimethyl-(1,1,2-trimethyl-propyl)-silane

2-(3-hydroxy-4-methoxyphenyl)-1-(3',4',5'-trimethoxyphenyl)ethyne

(Z)-5-(2'-bromoethenyl)-2-methoxyphenol

Downstream raw materials:

erianin

{2-Methoxy-5-[(Z)-2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxycarbonylamino}-acetic acid ethyl ester

trans-combretastatin A-4

{(S)-1-[(S)-1-(4-{2-Methoxy-5-[(Z)-2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxymethyl}-phenylcarbamoyl)-4-ureido-butylcarbamoyl]-2-methyl-propyl}-carbamic acid benzyl ester

Refernces

• 1、 Huang, Xiaochao,Wang, Meng,Wang, Chungu,Hu, Weiwei,You, Qinghong,Yang, Yong,Yu, Chunhao,Liao, Zhixin,Gou, Shaohua,Wang, Hengshan. "Dual-targeting antitumor conjugates derived from platinum(IV) prodrugs and microtubule inhibitor CA-4 significantly exhibited potent ability to overcome cisplatin resistance". . . Retrieved 2019.
• 2、 Petrov, Ognyan I.,Gerova, Mariana S.,Chanev, Christo D.,Petrova, Katya V.. "New efficient synthesis of combretastatin A-4 via Colvin rearrangement". . p. 3711 - 3715. Retrieved 2011.
• 3、 Mahesh, Rasala,Nayak, Vadithe Lakshma,Babu, Korrapati Suresh,Riyaz, Syed,Shaik, Thokhir Basha,Kumar, Gajjela Bharth,Mallipeddi, Prema Latha,Reddy, Challa Ratna,Shekar, Kunta Chandra,Jose, Jedy,Nagesh, Narayana,Kamal, Ahmed. "Design, Synthesis, and in vitro and in vivo Evaluations of (Z)-3,4,5-Trimethoxystyrylbenzenesulfonamides/sulfonates as Highly Potent Tubulin Polymerization Inhibitors". . p. 678 - 700. Retrieved 2017.
• 4、 Lawrence, Nicholas J.,Ghani, Fazni Abdul,Hepworth, Lucy A.,Hadfield, John A.,McGown, Alan T.,Pritchard, Robin G.. "The synthesis of (E) and (Z)-combretastatins A-4 and a phenanthrene from Combretum caffrum". . p. 1656 - 1660. Retrieved 1999.
• 5、 Baweja, Saral,Clauss, Reike,Gelman, Dmitri,Hey-Hawkins, Evamarie. "Heterobimetallic Pd/Mn and Pd/Co complexes as efficient and stereoselective catalysts for sequential Cu-free Sonogashira coupling–alkyne semi-hydrogenation reactions". . p. 1344 - 1356. Retrieved 2022/02/03.
• 6、 Huang, Jinwen,Huang, Leilei,Li, Yingzi,Nie, Hui,Song, Lixing,Wu, Fanhong. "Design, synthesis and biological evaluation of combretastatin A-4 sulfamate derivatives as potential anti-cancer agents". . p. 1374 - 1380. Retrieved 2021/09/30.