3482-37-9

Basic information

• Product Name: TRIMETHYLCOLCHICINIC ACID
• Synonyms: TRIMETHYLCOLCHICINIC ACID;7-amino-6,7-dihydro-10-hydroxy-1,2,3-trimethoxy-benzo(a)heptalen-9(5h)-on;deacetylcholchiceine;desacetylcholchiceine;n-deacetyl-colchicein;trimethyl-colchicinicaci;N-DEACETYLCOLCHICEINE;(S)-7-amino-6,7-dihydro-10-hydroxy-1,2,3-trimethoxybenzo[a]heptalen-9(5H)-one
• CAS NO: 3482-37-9
• Molecular Formula: C₁₉H₂₁NO₅
• Molecular Weight: 343.37
• EINECS: 222-464-5
• Product Categories: All Inhibitors;Inhibitors;AlkaloidsForensic and Veterinary Standards;Chemical Structure;Drugs of Abuse;Drugs&Metabolites;Neat CompoundsDrugs of Abuse;OthersAlphabetic;TP - TZ;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 3482-37-9.mol
• Article Data: 7

Chemical Properties

• Melting Point: >230°C (dec.)
• Boiling Point: 478.65°C (rough estimate)
• Flash Point: 334.2°C
• Appearance: /
• Density: 1.2726 (rough estimate)
• Vapor Pressure: 1.09E-16mmHg at 25°C
• Refractive Index: 1.5000 (estimate)
• Storage Temp.: −20°C
• Solubility: Chloroform (Slightly, Sonicated), DMSO (Slightly), Ethanol (Slightly), Methanol
• CAS DataBase Reference: TRIMETHYLCOLCHICINIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: TRIMETHYLCOLCHICINIC ACID(3482-37-9)
• EPA Substance Registry System: TRIMETHYLCOLCHICINIC ACID(3482-37-9)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36
• WGK Germany: 3
• RTECS: GH0960000
• Hazardous Substances Data: 3482-37-9(Hazardous Substances Data)

Usage

Description

A minor alkaloid of the colchicine class, this base was first isolated from the seeds and corms of Colchicum autumnale, Gloriosa virescens and Littoria modesta and subsequently by Russian workers from Merendera robusta Bge. Several specific rotations have been measured, e.g. [α]D - 184°, - 152° and - 180° (all in CHC13). The base is separated from the numerous accompanying alkaloids by chromatography and countercurrent distribution.

Chemical Properties

Yellow-green Solid

Uses

An antimitotic agent that disrupts microtubles by binding to tubulin and preventing its polymerization. Stimulates the intrinsic GTPase activity of tubulin. Induces apoptosis in several normal and tumor cell lines and activates the JNK/SAPK signaling pathway.

References

Potesilova, Hrbek, Santavy, Collect. Czech. Chem. Commun., 32, 141 (1967) Trudykulov, Yusupov, Sadykov, Khim. Prir. Soedin., 8,247 (1972) Yusupov, Tr. Tashkent Fan., Uzbek SSR, 20, 24 (1972)

InChI:InChI=1/C19H21NO5/c1-23-16-8-10-4-6-13(20)12-9-15(22)14(21)7-5-11(12)17(10)19(25-3)18(16)24-2/h5,7-9,13H,4,6,20H2,1-3H3,(H,21,22)/t13-/m0/s1

Upstream product

• 73307-44-5 7-amino-10-hydroxy-1,2,3-trimethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one 
• 7647-01-0 hydrogenchloride 
• 67-56-1 methanol 
• 64-86-8 colchicine 
• 7664-93-9 sulfuric acid 
• 477-27-0 colchiceine 
• 518-12-7 (7S)-isocolchicine 
• 7469-68-3 (S)-7-((Ξ)-benzylidenamino)-10-hydroxy-1,2,3-trimethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one 

Downstream Products

• 477-27-0 (+)-colchiceine 
• 477-27-0 colchiceine 
• 86495-10-5 N-((S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-propionamide 
• 518-11-6 demecolceine 
• 477-30-5 (-)-demecolcine 
• 4702-33-4 isodemecolcine 
• 3476-50-4 deacetylcolchicine 
• 47477-04-3 (-)-N-deacetylisocolchicine 
• 75520-89-7 (+)-colchicine 
• 1850-58-4 7-oxodeacetamidoisocolchicine 
• 1850-57-3 7-desacetamido-7-oxocolchicine 
• 74515-40-5 colchifoline 

Relevant articles and documents

Discovery of structurally simplified analogs of colchicine as an immunosuppressant

We have discovered a new class of colchicine-derived therapeutic agents for immune diseases including rejection of organ-transplantation and autoimmune disease. Compound 2, which had been developed to overcome poor pharmacokinetic properties of compound 1, a first-generation colchicine analog, turned out to show toxicity such as intestinal toxicity and loss of weight during in vivo tests. The deletion of 7-carboxamide group and middle ring-truncation in colchicine allowed us to have structurally simplified analogs with strong immunosuppressive activity. Herein, we report non-alkaloid tricyclic compound 7 and 12 as immunosuppressants which exhibited a strong immunosuppressive in vivo efficacy on the T-dependent antibody response, the Zymosan A-induced arthritis model and the Carrageenan-induced edema model. Compound 7 and 12 revealed less toxicity than the previous lead compound 2, and their minimum lethal doses (MLD) were proved to exceed 100 mg/kg.

Synthesis and evaluation of 90Y-DOTA-colchicine conjugate in murine fibrosarcoma model

Colchicine is a cytotoxic bioactive alkaloid that exhibits its action by microtubular binding. With an aim to develop a tumor targeted radio-therapeutic agent, colchicine has been functionalized to trimethylcolchicinic acid and conjugated to the isothiocyanato derivative of DOTA (1,4,7,10-tetraaza cyclododecane tetracetic acid). DOTA coupled colchicine was radiolabeled with 90Y, one of the most commonly used therapeutic radioisotope. Complexation of 200 μg of the conjugate with 90Y was carried out at pH 4.5 with an incubation time of 45 min at 70°C. Complexation yield of 90Y-DOTA-NCS-colchicine was confirmed to be >98% using C-18 reverse phase HPLC system. 90Y-colchicine complex could be differentiated from 90Y-p-NCS-benzyl-DOTA on the basis of difference in their retention times 8 and 4 min, respectively in a standardized HPLC system. Biodistribution studies in Swiss mice fibrosarcoma tumor model showed an uptake of ～0.8% ID/g tumor at 3 h.p.i. that was retained till 24 h.p.i. 90Y-DOTA-NCS-colchicine complex showed excellent pharmacokinetics with major portion of the radioactivity being excreted out within 3 h.p.i. and no accumulation of radioactivity in vital organs. Copyright

Syntheses of colchicine and isocolchicine labelled with carbon-11 or carbon-13

The syntheses of isotopically labelled (-)-10-[11C/13C]-colchicine and (-)-9-[11C/13C]-isocolchicine have been achieved from the reaction of (-)desmethylcolchicine with [11C/13C]-iodomethane. The radiolabelled compounds, (-)-10-[11C]-colchicine (11C-n-colchicine) and (-)-9-[11C]-isocolchicine (11C-i-colchicine), were isolated by reversed phase HPLC. The total synthesis time was approximately 60 minutes for both radiolabelled compounds with an average specific activity of 240 mCi/μmol calculated to EOB. Utilizing a similar synthetic strategy, we also report the synthesis of milligram quantities of the carbon-13 enriched compounds and the magnetic resonance signal assignment for (-)-9-[13C] isocolchicine.