Colchicine

Base Information

• Chemical Name: Colchicine
• CAS No.: 64-86-8
• Deprecated CAS: 30512-31-3,5843-86-7
• Molecular Formula: C22H25NO6
• Molecular Weight: 399.444
• Hs Code.: 29399990
• European Community (EC) Number: 200-598-5
• NSC Number: 756702,757
• UN Number: 1544
• UNII: SML2Y3J35T
• DSSTox Substance ID: DTXSID5024845
• Nikkaji Number: J9.267C
• Wikipedia: Colchicine
• Wikidata: Q326224
• NCI Thesaurus Code: C385
• RXCUI: 2683
• Pharos Ligand ID: H8JH9SUA1QP3
• Metabolomics Workbench ID: 51495
• ChEMBL ID: CHEMBL107
• Mol file: 64-86-8.mol

Synonyms:Colchicine;Colchicine, (+-)-Isomer;Colchicine, (R)-Isomer

Chemical Property of Colchicine

Chemical Property:

• Appearance/Colour: Yellow solid
• Vapor Pressure: 6.21E-21mmHg at 25°C
• Melting Point: 150-160 °C (dec.)(lit.)
• Refractive Index: 1.584
• Boiling Point: 726 °C at 760 mmHg
• PKA: 12.36(at 20℃)
• Flash Point: 392.9 °C
• PSA: 83.09000
• Density: 1.25 g/cm³
• LogP: 3.26250
• Storage Temp.: Poison room
• Sensitive.: Light Sensitive
• Solubility.: H2O: 10 mg/mL
• Water Solubility.: 45 g/L (20 ºC)
• XLogP3: 1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 399.16818752
• Heavy Atom Count: 29
• Complexity: 740
• Transport DOT Label: Poison

Purity/Quality:

98% ^*data from raw suppliers

(S)-Colchicine>95% ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, T+
• Hazard Codes: T+,T,Xi
• Statements: 26/28-41-46
• Safety Statements: 13-45-36/37/39-28-26-53

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antigout Agents/Gout Suppressants
• Canonical SMILES: CC(=O)NC1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)OC)OC)OC)OC
• Isomeric SMILES: CC(=O)N[C@H]1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)OC)OC)OC)OC
• Recent ClinicalTrials: Colchicine to Suppress Inflammation and Improve Insulin Resistance in Adults and Adolescents With Obesity
• Recent EU Clinical Trials: Evaluation of low dose colchicine and ticagrelor in prevention of ischemic stroke in patients with stroke due to atherosclerosis.
• Recent NIPH Clinical Trials: Colchicine for preventing respiratory failure in COVID-19 with fever
• Uses: It can be used for the study of plant genetics; used as selenium reagent; clinically as anticancer drugs. The product is a typical mitosis toxin. It can be used for treating acute gout and breast cancer. It can also be used as selenium reagent, for being applied to plant genetics and cancer research. It is a kind of antineoplastic agents and anti-gout for being used for the treatment acute gout and for the treatment of tumors Colchicine is present in the poisonous autumncrocus (meadow saffron). It is the major alkaloid of Colchicum autumnale L. and Liliaceae. It was used in poison potions in theancient kingdom of Colchis (Greece). It isused therapeutically as an antineoplast, for thesuppression of gout, and in the treatment ofMediterranean fever. It is used in plant studiesfor doubling chromosome groups. Binds specifically with tubulin thus interfering with microtubule organization. antimitotic, antigout agent anti-inflammatory agent, mitosis inhibitor For treatment and relief of pain in attacks of acute gouty arthritis. In research in plant genetics (for doubling chromosomes).
• Production method: This product is a kind of alkaloid extracted from the crom or seed of the lily family plants, Colchicum autumnale. The Colchicum autumnale powder was heated under reflux with 85% ethanol extraction for 4h, the resulted ethanol solution was concentrated under reduced pressure to a semi-gum, dilute with distilled water, with 10% sulfuric acid acidified filtrate with extraction by chloroform, and then concentrate the chloroform extract, the resulted crude colchicine obtained by crystallization was subject to re-crystallization to obtain the finished product. Calculated from the Colchicum autumnale powder, the total yield is 0.15%. In foreign countries, it is mostly extracted from the crom of the Liliaceae Colchicum genus Colchicum bulbs. Take the bulbs and seeds of Iphigenia indica or Colchicum autumnale as raw material; obtain the final product with ethanol extraction and refining.
• Description: Colchicine is a pale-yellow powder that is obtained from various species of Colchicum, primarily Colchicum autumnale L. Its total chemical synthesis has been achieved, but the primary source of colchicine currently remains alcohol extraction of the alkaloid from the corm and seed of C. autumnale L. It darkens on exposure to light and possesses
• Physical properties: Appearance: colchicine exists in white or light-yellow crystal powder with no smell, and it is seldom prone to absorb moisture. Melting point: it becomes dark when it is exposed to light, and it melts at 87–89?°C. Solubility: this product is soluble in chloroform or ethanol and it dissolves in water. However, the semihydrate crystal can form in certain concentrations. The product is hardly soluble in ether. Specific optical rotation: ?121° (0.9?g/100?mL, chloroform, 589.3?nm, 17?°C).
• Indications: Colchicine, an alkaloid obtained from the autumn crocus, has long been used and is relatively selective for the treatment of acute gouty arthritis. Unlike many of the newer agents for use in gout, colchicine has minimal effects on uric acid synthesis and excretion; it decreases inflammation associated with this disorder. It is thought that colchicine somehow prevents the release of the chemotactic factors and/or inflammatory cytokines from the neutrophils, and this in turn decreases the attraction of more neutrophils into the affected area .The ability of colchicine to bind to leukocyte microtubules in a reversible covalent complex and cause their depolymerization also may be a factor in decreasing the attraction of the motile leukocytes into the inflamed area.
• Biological Functions: Acting on polymorphonuclear leukocytes and diminishing phagocytosis, it inhibits the production of lactic acid, causing an increase in the pH of synovial tissue and, thus, a decrease in urate deposition, because uric acid is more soluble at the higher pH. Additionally, colchicine inhibits the release of lysosomal enzymes during phagocytosis that also contributes to the reduction of inflammation. Because colchicine does not lower serum urate levels, it has been found to be beneficial to combine colchicine with a uricosuric agent, particularly probenecid. It is a potent drug, being effective at doses of approximately 1 mg, but doses as small as 7 mg have caused fatalities.
• Clinical Use: The major use of colchicine is as an antiinflammatory agent in the treatment of acute gouty arthritis; it is not effective in reducing inflammation in other disorders. It also can be used to prevent attacks. Since colchicine is so rapidly effective in relieving the acute symptoms of gout (substantial improvement is achieved within hours), it has been used as a diagnostic aid in this disorder. Therapy with colchicine is usually begun at the first sign of an attack and is continued until symptoms subside, adverse gastrointestinal reactions appear, or a maximum dose of 6 to 7 mg has been reached.
• Drug interactions: Potentially hazardous interactions with other drugs Anti-arrhythmics: possible increased risk of toxicity with amiodarone. Antibacterials: possible increased risk of toxicity with azithromycin, clarithromycin, erythromycin and telithromycin - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure. Antifungals: possible increased risk of toxicity with itraconazole and ketoconazole - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure. Antivirals: possible increased risk of toxicity with atazanavir, indinavir, ritonavir and telaprevir - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure. Calcium-channel blockers: possible increased risk of toxicity with diltiazem and verapamil - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure. Cardiac glycosides: possible increased risk of myopathy with digoxin. Ciclosporin: risk of myopathy or rhabdomyolysis, also increased blood-ciclosporin concentrations and nephrotoxicity - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure. Grapefruit juice: possible increased risk of toxicity. Lipid-regulating drugs: possible increased risk of myopathy with fibrates and statins.

Technology Process of Colchicine

There total 80 articles about Colchicine 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%

acetic anhydride (108-24-7) + (S)-tert-butyl N-(1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalene-7-yl)carbamate (186374-95-8) → colchicine (64-86-8,54192-66-4)

Guidance literature:

(S)-tert-butyl N-(1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalene-7-yl)carbamate; With hydrogenchloride; In diethyl ether; at 20 ℃; for 1h;

acetic anhydride; With dmap; triethylamine; In diethyl ether; at 25 ℃; for 10h;

DOI:10.1016/S0040-4020(00)00862-0

Reference yield: 85.0%

methoxymagnesium bromide + 10-demethoxy-10-tosylcolchicine → colchicine (64-86-8,54192-66-4)

Guidance literature:

In tetrahydrofuran; for 5h;

DOI:10.1021/jm00058a013

Reference yield: 81.0%

C22H27NO7 → colchicine (64-86-8,54192-66-4)

Guidance literature:

With N,N-dimethyl-ethanamine; trimethylsilyl trifluoromethanesulfonate; In dichloromethane; at 20 ℃; for 12h; Inert atmosphere;

DOI:10.1021/acs.orglett.7b02224

upstream raw materials:

diazomethane

diethyl ether

chloroform

colchiceine

Downstream raw materials:

(+)-α-lumicolchicine

β-lumicolchicine

lumicolchicine

thiocolchicine

Refernces

• 1、 -. "SEMISYNTHETIC PROCESS FOR THE PREPARATION OF COLCHICINE". Page/Page column 11; 12. . Retrieved 2022/01/05.
• 2、 Liu, Xin,Hu, Ya-Jian,Chen, Bo,Min, Long,Peng, Xiao-Shui,Zhao, Jing,Li, Shaoping,Wong, Henry N. C.,Li, Chuang-Chuang. "Asymmetric Total Syntheses of Colchicine, β-Lumicolchicine, and Allocolchicinoid N-Acetylcolchinol-O-methyl Ether (NCME)". . p. 4612 - 4615. Retrieved 2017/09/12.