64-86-8

Basic information

• Product Name: Colchicine
• Synonyms: (S)-N-(5,6,7,9-TETRAHYDRO-1,2,3,10-TETRAMETHOXY-9-OXOBENZO[A]HEPTALEN-7-YL)ACETAMIDE;N-((S)-1,2,3,10-TETRAMETHOXY-9-OXO-5,6,7,9-TETRAHYDRO-BENZO[A]HEPTALEN-7-YL)-ACETAMIDE;n-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl)-acetamide;7-acetamido-6,7-dihydro-1,2,3,10-tetramethoxy-benzo(a)heptalen-9(5h)-on;7-alpha-h-colchicine;7alpha-h-colchicine;7alphaH-Colchicine;Acetamide, N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(alpha)heptalen-7-yl)-
• CAS NO: 64-86-8
• Molecular Formula: C₂₂H₂₅NO₆
• Molecular Weight: 399.44
• EINECS: 200-598-5
• Product Categories: Alkaloids;All Inhibitors;Alkaloids (Others);Biochemistry;Plant Growth Regulators;Plant Growth Trgulators (Others);Tropolones;Tropolones & Azulenes;Antibiotic Explorer;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;API's;Antitumor Agents;Cell Signaling and Neuroscience;Cytoskeleton and Extracellular Matrix;Microtobule InhibitorsCancer Research;Microtubule Inhibitors;Caspases/Apoptosis;Amines;Chiral Reagents;Heterocycles;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;plantgrowth;#N/A
• Mol File: 64-86-8.mol
• Article Data: 15

Chemical Properties

• Melting Point: 150-160 °C (dec.)(lit.)
• Boiling Point: 522.37°C (rough estimate)
• Flash Point: 392.9 °C
• Appearance: white to yellow with a green cast/powder
• Density: 1.2770 (rough estimate)
• Vapor Pressure: 6.21E-21mmHg at 25°C
• Refractive Index: 1.5614 (estimate)
• Storage Temp.: Poison room
• Solubility: H2O: 10 mg/mL
• PKA: 12.36(at 20℃)
• Water Solubility: 45 g/L (20 ºC)
• Sensitive: Light Sensitive
• Stability: Stable. Light sensitive. Incompatible with strong oxidizing agents.
• Merck: 14,2471
• BRN: 2228813
• CAS DataBase Reference: Colchicine(CAS DataBase Reference)
• NIST Chemistry Reference: Colchicine(64-86-8)
• EPA Substance Registry System: Colchicine(64-86-8)

Safety Data

• Hazard Codes: T+,T,Xi
• Statements: 26/28-41-46
• Safety Statements: 13-45-36/37/39-28-26-53
• RIDADR: UN 1544 6.1/PG 1
• WGK Germany: 3
• RTECS: GH0700000
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: I
• Hazardous Substances Data: 64-86-8(Hazardous Substances Data)

Usage

Chemical Description

Colchicine is a well-known alkaloid used in medicine for its anti-inflammatory and anti-tumor properties.

InChI:InChI=1/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m0/s1

Synthetic route

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)

Conditions	Yield
Stage #1: (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; Stage #2: acetic anhydride With dmap; triethylamine In diethyl ether at 25℃; for 10h;	98%

methoxymagnesium bromide + 10-demethoxy-10-tosylcolchicine → colchicine (64-86-8)

Conditions	Yield
In tetrahydrofuran for 5h;	85%

C22H27NO7 → colchicine (64-86-8)

Conditions	Yield
With N,N-dimethyl-ethanamine; trimethylsilyl trifluoromethanesulfonate In dichloromethane at 20℃; for 12h; Inert atmosphere;	81%
With N,N-dimethyl-ethanamine; trimethylsilyl trifluoromethanesulfonate In dichloromethane	81%
With trimethylsilyl trifluoromethanesulfonate; triethylamine In dichloromethane at 20℃; for 2h;	75%

magnesium methanolate (109-88-6, 16436-83-2, 16436-85-4) + 10-demethoxy-10-tosylcolchicine → colchicine (64-86-8)

Conditions	Yield
In methanol	78%

diazomethane (186581-53-3, 908094-01-9) + diethyl ether (60-29-7) + chloroform (67-66-3) + colchiceine (477-27-0, 1990-46-1) → colchicine (64-86-8) + (7S)-isocolchicine (518-12-7)

diazomethane (186581-53-3, 908094-01-9) + colchiceine (477-27-0, 1990-46-1) → colchicine (64-86-8) + (7S)-isocolchicine (518-12-7)

Conditions	Yield
With diethyl ether; chloroform

diazomethane (186581-53-3, 908094-01-9) + 2,10-didemethylcolchicine (33530-04-0) → colchicine (64-86-8) + 2-demethylcolchicine (7336-36-9) + (7S)-isocolchicine (518-12-7) + 2-demethylisocolchicine (142713-50-6)

Conditions	Yield
In diethyl ether; chloroform

<1-3H>-3-phenylpropanal (133946-40-4) → colchicine (64-86-8)

Conditions	Yield
Colchicum byzantinum biosynthesis;

<3-14C>-cinnamic acid (4469-06-1) → colchicine (64-86-8)

Conditions	Yield
Colchicum byzantinum biosynthesis;

deacetylcolchicine (3476-50-4) + acetic anhydride (108-24-7) → colchicine (64-86-8)

Conditions	Yield
With sodium hydrogencarbonate In chloroform; water for 2.5h;
Acetylation;

<1-3H>-3-phenylprop-2-enal (133946-39-1) → colchicine (64-86-8)

Conditions	Yield
Colchicum byzantinum biosynthesis;

<3-14C>-3-phenylpropionic acid (131946-50-4) → colchicine (64-86-8)

Conditions	Yield
Colchicum byzantinum biosynthesis;

DL-phenylalanine (13744-69-9) → colchicine (64-86-8)

Conditions	Yield
Colchicum byzantinum biosynthesis;

colchicine-β-cyclodextrin complex → colchicine (64-86-8) + β‐cyclodextrin (7585-39-9)

Conditions	Yield
at 25 - 60℃; Equilibrium constant;

diazomethane (186581-53-3, 908094-01-9) + (-)-O2-demethyl-colchicine → colchicine (64-86-8)

Conditions	Yield
With methanol; diethyl ether

diazomethane (186581-53-3, 908094-01-9) + (-)-O3-demethyl-colchicine → colchicine (64-86-8)

Conditions	Yield
With methanol; diethyl ether

3-(3,4,5-trimethoxyphenyl)propan-1-ol (53560-26-2) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 17 steps 1.1: 98 percent / 2,6-lutidine / CH2Cl2 / 5 h / 20 °C 2.1: 95 percent / silver trifluoroacetate; I2; sodium bicarbonate / CHCl3 / 3 h / 0 °C 3.1: 92 percent / Et2NH; bis[triphenylphosphine]palladium dichloride; copper(I) iodide / dimethylsulfoxide / 20 h / 90 °C 4.1: 98 percent / n-Bu4NF / tetrahydrofuran / 7 h / 20 °C 5.1: 96 percent / oxalyl chloride; DMSO / CH2Cl2 / 0.75 h / -78 °C 6.1: BH3*THF / tetrahydrofuran / 1 h / 20 °C 6.2: t-BuLi / pentane; tetrahydrofuran / 0.67 h / -78 °C 6.3: 64 percent / tetrahydrofuran; pentane / 3 h / -78 °C 7.1: 96 percent / oxalyl chloride; DMSO / CH2Cl2 / 0.5 h / -78 °C 8.1: 85 percent / BH3*THF; (S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol / tetrahydrofuran / 6 h / 23 °C 9.1: 60 percent / diphenylphosphoryl azide; triphenylphosphine; diisopropylazodicarboxylate / tetrahydrofuran / 12 h / 20 °C 10.1: 95 percent / Ph3P / tetrahydrofuran; H2O / 50 h / 20 °C 11.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 12.1: 60 percent / various solvent(s) / 66 h / Heating 13.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 14.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 15.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 16.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 17.1: HCl / diethyl ether / 1 h / 20 °C 17.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 18 steps 1: 2,6-lutidine 2: I2; CF3CO2Ag / CHCl3 3: Et2NH; CuI / (Ph3P)2PdCl2 / dimethylsulfoxide 4: TBAF / tetrahydrofuran 5: (COCl)2; DMSO; Et3N 7: (COCl)2; DMSO; Et3N 9: 64 percent / PPh3; DEAD; (PhO)2P(O)N3 10: Ph3P; H2O 11: Et3N 12: 70 percent / 1,2-dichloro-benzene / Heating 13: LiOH 15: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 16: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 17: HCl View Scheme

3,4,5-Trimethoxybenzoyl chloride (4521-61-3) → colchicine (64-86-8)

Conditions

Yield

Multi-step reaction with 15 steps 1.1: zinc-copper couple / benzene; N,N-dimethyl-acetamide / 3 h / 20 °C / sonication 1.2: 31 percent / bis(triphenylphosphine)palladium dichloride / benzene; N,N-dimethyl-acetamide / 2 h / sonication 2.1: 91 percent / H2 / Pd/C / ethanol; H2O / 22 h / 3102.89 Torr 3.1: 93 percent / NaHCO3; silver trifluoroacetate; I2 / CHCl3 / 2 h / 0 °C 4.1: trifluoroacetic acid / diethyl ether / 3 h / 20 °C 5.1: 454 mg / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h 6.1: 60 percent / Et2NH; bis[triphenylphosphine]palladium dichloride; copper(I) iodide / dimethylsulfoxide / 15 h / 90 °C 7.1: 91 percent / potassium carbonate / methanol / 11 h / 20 °C 8.1: 100 percent / DIBAL / CH2Cl2; hexane / 1 h / -78 °C 9.1: potassium carbonate / methanol / 1 h / Heating 9.2: 64 percent / KOH / methanol / 3 h / Heating 10.1: 70 percent / various solvent(s) / 40 h / Heating 11.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 12.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 13.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 14.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 15.1: HCl / diethyl ether / 1 h / 20 °C 15.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme

3-(2-ethynyl-3,4,5-trimethoxy-phenyl)-propionaldehyde (327024-99-7) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 12 steps 1.1: BH3*THF / tetrahydrofuran / 1 h / 20 °C 1.2: t-BuLi / pentane; tetrahydrofuran / 0.67 h / -78 °C 1.3: 64 percent / tetrahydrofuran; pentane / 3 h / -78 °C 2.1: 96 percent / oxalyl chloride; DMSO / CH2Cl2 / 0.5 h / -78 °C 3.1: 85 percent / BH3*THF; (S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol / tetrahydrofuran / 6 h / 23 °C 4.1: 60 percent / diphenylphosphoryl azide; triphenylphosphine; diisopropylazodicarboxylate / tetrahydrofuran / 12 h / 20 °C 5.1: 95 percent / Ph3P / tetrahydrofuran; H2O / 50 h / 20 °C 6.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 7.1: 60 percent / various solvent(s) / 66 h / Heating 8.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 9.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 10.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 11.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 12.1: HCl / diethyl ether / 1 h / 20 °C 12.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 13 steps 2: (COCl)2; DMSO; Et3N 4: 64 percent / PPh3; DEAD; (PhO)2P(O)N3 5: Ph3P; H2O 6: Et3N 7: 70 percent / 1,2-dichloro-benzene / Heating 8: LiOH 10: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 11: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 12: HCl View Scheme

3-(2-ethynyl-3,4,5-trimethoxyphenyl)propan-1-ol (206195-25-7) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 13 steps 1.1: 96 percent / oxalyl chloride; DMSO / CH2Cl2 / 0.75 h / -78 °C 2.1: BH3*THF / tetrahydrofuran / 1 h / 20 °C 2.2: t-BuLi / pentane; tetrahydrofuran / 0.67 h / -78 °C 2.3: 64 percent / tetrahydrofuran; pentane / 3 h / -78 °C 3.1: 96 percent / oxalyl chloride; DMSO / CH2Cl2 / 0.5 h / -78 °C 4.1: 85 percent / BH3*THF; (S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol / tetrahydrofuran / 6 h / 23 °C 5.1: 60 percent / diphenylphosphoryl azide; triphenylphosphine; diisopropylazodicarboxylate / tetrahydrofuran / 12 h / 20 °C 6.1: 95 percent / Ph3P / tetrahydrofuran; H2O / 50 h / 20 °C 7.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 8.1: 60 percent / various solvent(s) / 66 h / Heating 9.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 10.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 11.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 12.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 13.1: HCl / diethyl ether / 1 h / 20 °C 13.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 14 steps 1: (COCl)2; DMSO; Et3N 3: (COCl)2; DMSO; Et3N 5: 64 percent / PPh3; DEAD; (PhO)2P(O)N3 6: Ph3P; H2O 7: Et3N 8: 70 percent / 1,2-dichloro-benzene / Heating 9: LiOH 11: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 12: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 13: HCl View Scheme

3-(2-ethynyl-3,4,5-trimethoxy-phenyl)-1-oxazol-2-yl-propan-1-one → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: 85 percent / BH3*THF; (S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol / tetrahydrofuran / 6 h / 23 °C 2.1: 60 percent / diphenylphosphoryl azide; triphenylphosphine; diisopropylazodicarboxylate / tetrahydrofuran / 12 h / 20 °C 3.1: 95 percent / Ph3P / tetrahydrofuran; H2O / 50 h / 20 °C 4.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 5.1: 60 percent / various solvent(s) / 66 h / Heating 6.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 7.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 8.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 9.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 10.1: HCl / diethyl ether / 1 h / 20 °C 10.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 11 steps 2: 64 percent / PPh3; DEAD; (PhO)2P(O)N3 3: Ph3P; H2O 4: Et3N 5: 70 percent / 1,2-dichloro-benzene / Heating 6: LiOH 8: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 9: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 10: HCl View Scheme

3-(2-ethynyl-3,4,5-trimethoxyphenyl)-1-(1,3-oxazol-2-yl)propan-1-ol (206195-28-0) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 11 steps 1.1: 96 percent / oxalyl chloride; DMSO / CH2Cl2 / 0.5 h / -78 °C 2.1: 85 percent / BH3*THF; (S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol / tetrahydrofuran / 6 h / 23 °C 3.1: 60 percent / diphenylphosphoryl azide; triphenylphosphine; diisopropylazodicarboxylate / tetrahydrofuran / 12 h / 20 °C 4.1: 95 percent / Ph3P / tetrahydrofuran; H2O / 50 h / 20 °C 5.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 6.1: 60 percent / various solvent(s) / 66 h / Heating 7.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 8.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 9.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 10.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 11.1: HCl / diethyl ether / 1 h / 20 °C 11.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 12 steps 1: (COCl)2; DMSO; Et3N 3: 64 percent / PPh3; DEAD; (PhO)2P(O)N3 4: Ph3P; H2O 5: Et3N 6: 70 percent / 1,2-dichloro-benzene / Heating 7: LiOH 9: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 10: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 11: HCl View Scheme

triisopropyl-[3-(3,4,5-trimethoxy-phenyl)-propoxy]-silane (327025-17-2) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 16 steps 1.1: 95 percent / silver trifluoroacetate; I2; sodium bicarbonate / CHCl3 / 3 h / 0 °C 2.1: 92 percent / Et2NH; bis[triphenylphosphine]palladium dichloride; copper(I) iodide / dimethylsulfoxide / 20 h / 90 °C 3.1: 98 percent / n-Bu4NF / tetrahydrofuran / 7 h / 20 °C 4.1: 96 percent / oxalyl chloride; DMSO / CH2Cl2 / 0.75 h / -78 °C 5.1: BH3*THF / tetrahydrofuran / 1 h / 20 °C 5.2: t-BuLi / pentane; tetrahydrofuran / 0.67 h / -78 °C 5.3: 64 percent / tetrahydrofuran; pentane / 3 h / -78 °C 6.1: 96 percent / oxalyl chloride; DMSO / CH2Cl2 / 0.5 h / -78 °C 7.1: 85 percent / BH3*THF; (S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol / tetrahydrofuran / 6 h / 23 °C 8.1: 60 percent / diphenylphosphoryl azide; triphenylphosphine; diisopropylazodicarboxylate / tetrahydrofuran / 12 h / 20 °C 9.1: 95 percent / Ph3P / tetrahydrofuran; H2O / 50 h / 20 °C 10.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 11.1: 60 percent / various solvent(s) / 66 h / Heating 12.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 13.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 14.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 15.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 16.1: HCl / diethyl ether / 1 h / 20 °C 16.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 17 steps 1: I2; CF3CO2Ag / CHCl3 2: Et2NH; CuI / (Ph3P)2PdCl2 / dimethylsulfoxide 3: TBAF / tetrahydrofuran 4: (COCl)2; DMSO; Et3N 6: (COCl)2; DMSO; Et3N 8: 64 percent / PPh3; DEAD; (PhO)2P(O)N3 9: Ph3P; H2O 10: Et3N 11: 70 percent / 1,2-dichloro-benzene / Heating 12: LiOH 14: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 15: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 16: HCl View Scheme

5-[(3S)-3-azido-3-(1,3-oxazol-2-yl)propyl]-4-ethynyl-1,2,3-trimethoxybenzene (206195-32-6) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: 95 percent / Ph3P / tetrahydrofuran; H2O / 50 h / 20 °C 2.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 3.1: 60 percent / various solvent(s) / 66 h / Heating 4.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 5.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 6.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 7.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 8.1: HCl / diethyl ether / 1 h / 20 °C 8.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 9 steps 1: Ph3P; H2O 2: Et3N 3: 70 percent / 1,2-dichloro-benzene / Heating 4: LiOH 6: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 7: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 8: HCl View Scheme

(S)-3-(2-Ethynyl-3,4,5-trimethoxy-phenyl)-1-oxazol-2-yl-propylamine (327024-98-6) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 2.1: 60 percent / various solvent(s) / 66 h / Heating 3.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 4.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 5.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 6.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 7.1: HCl / diethyl ether / 1 h / 20 °C 7.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 8 steps 1: Et3N 2: 70 percent / 1,2-dichloro-benzene / Heating 3: LiOH 5: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 6: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 7: HCl View Scheme

(1R)-3-(2-ethynyl-3,4,5-trimethoxyphenyl)-1-(1,3-oxazol-2-yl)propan-1-ol (206195-30-4) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 9 steps 1.1: 60 percent / diphenylphosphoryl azide; triphenylphosphine; diisopropylazodicarboxylate / tetrahydrofuran / 12 h / 20 °C 2.1: 95 percent / Ph3P / tetrahydrofuran; H2O / 50 h / 20 °C 3.1: 98 percent / DMAP; Et3N / diethyl ether / 7 h / 20 °C 4.1: 60 percent / various solvent(s) / 66 h / Heating 5.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 6.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 7.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 8.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 9.1: HCl / diethyl ether / 1 h / 20 °C 9.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 10 steps 1: 64 percent / PPh3; DEAD; (PhO)2P(O)N3 2: Ph3P; H2O 3: Et3N 4: 70 percent / 1,2-dichloro-benzene / Heating 5: LiOH 7: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 8: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 9: HCl View Scheme

(S)-N-7-acetylamino-12,13,14-trimethoxy-5-oxatricyclo[8.4.0.02,6]tetradeca-1(10),2(6),3,11,13-pentaene (206195-21-3) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 2.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 3.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 4.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 5.1: HCl / diethyl ether / 1 h / 20 °C 5.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 6 steps 1: LiOH 3: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 4: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 5: HCl View Scheme

(S)-N-acetyl-3-(2-ethynyl-3,4,5-trimethoxyphenyl)-1-(2-oxazolyl)-propylamine (206195-23-5) → colchicine (64-86-8)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 60 percent / various solvent(s) / 66 h / Heating 2.1: 99 percent / Et3N; 4-(dimethylamino)pyridine / CH2Cl2 / 10 h / 35 °C 3.1: 99 percent / aq. LiOH / tetrahydrofuran / 12 h 4.1: 45 percent Turnov. / trimethylsilyltriflate / various solvent(s) / -78 - -60 °C 5.1: 62 percent / Et3N; trimethylsilyl triflate / CH2Cl2 / 2 h / 0 °C 6.1: HCl / diethyl ether / 1 h / 20 °C 6.2: 98 percent / 4-(dimethylamino)pyridine; Et3N / diethyl ether / 10 h / 25 °C View Scheme
Multi-step reaction with 7 steps 1: 70 percent / 1,2-dichloro-benzene / Heating 2: LiOH 4: 45 percent / TMSOTf / various solvent(s) / -78 - -50 °C 5: 62 percent / TMSOTf; Et3N / CH2Cl2 / 0 - 10 °C 6: HCl View Scheme

colchicine (64-86-8) → N-[(7S)-1,2,3-trimethoxy-9-oxo-10-amino-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide (3123-89-5)

Conditions	Yield
With ammonium hydroxide In ethanol for 12h; Reflux;	100%
With ammonium hydroxide In methanol at 20℃;	90%
With ammonium hydroxide In ethanol at 110℃; for 0.25h; Microwave irradiation;	75%

colchicine (64-86-8) → allocolchicinic acid (6714-14-3)

Conditions	Yield
With sodium methylate In methanol at 65℃; for 4h;	100%
With methanol; sodium methylate In water at 65℃;	99%
With methanol; water; sodium methylate

Dichloromethyl methyl ether (4885-02-3) + colchicine (64-86-8) → 4-Formylcolchicine (2730-82-7)

Conditions	Yield
With tin(IV) chloride In dichloromethane	100%
With tin(IV) chloride In dichloromethane at 20℃; for 13h; Cooling with ice; Inert atmosphere;	100%
With tin(IV) chloride In dichloromethane 0 deg C, 30 min., r.t. 15 h;	90%
With tin(IV) chloride In dichloromethane at 20℃;

di-tert-butyl dicarbonate (24424-99-5) + colchicine (64-86-8) → (S)-tert-butyl-N-acetyl(1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalene-7-yl)carbamate (186374-94-7)

Conditions	Yield
With dmap; triethylamine In acetonitrile at 100℃; for 7.5h;	100%
With dmap; triethylamine In acetonitrile at 100℃; Inert atmosphere;	98%
With dmap; triethylamine In tetrahydrofuran for 2h; Reflux;	97.5%

formaldehyd (50-00-0) + colchicine (64-86-8) + urethane (51-79-6) → ethyl {[(7S)-7-(acetylamino)-5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-4-yl]methyl}carbamate

Conditions	Yield
Stage #1: formaldehyd; urethane With sulfuric acid; water at 20℃; for 0.166667h; Stage #2: colchicine at 20℃; for 4h;	99%

colchicine (64-86-8) → 4-Bromocolchicine (1267993-28-1)

Conditions	Yield
With N-Bromosuccinimide; acetic acid	99%
With N-Bromosuccinimide; acetic acid; trifluoroacetic acid at 20℃; for 1h; Schlenk technique; Inert atmosphere;	95%
With N-Bromosuccinimide; acetic acid; trifluoroacetic acid In trifluoroacetic acid at 20℃; for 1h; Schlenk technique; Inert atmosphere;	95%

colchicine (64-86-8) → 4-Iodocolchicine (1267993-31-6)

Conditions	Yield
With N-iodo-succinimide; acetic acid	99%
With N-iodo-succinimide; acetic acid at 70℃; for 7h; Time; Inert atmosphere;	98.6%
With N-iodo-succinimide; acetic acid In acetonitrile at 70℃; for 20h; Inert atmosphere;	95%
With N-iodo-succinimide; acetic acid at 70℃; for 20h; Inert atmosphere;	95%
With N-iodo-succinimide; acetic acid at 70℃; for 7h;

[(S)-1-(2-aminoethyl)-pyrrolidin-2-yl]methanol (115531-70-9) + colchicine (64-86-8) → C28H37N3O6 (1415569-02-6)

Conditions	Yield
In dichloromethane at 70℃; for 4h;	99%

[(2R)-1-(2-aminoethyl)pyrrolidin-2-yl]methanol (867008-77-3) + colchicine (64-86-8) → C28H37N3O6 (1415569-03-7)

Conditions	Yield
In dichloromethane at 70℃; for 4h;	99%

colchicine (64-86-8) → colchiceine (477-27-0, 1990-46-1)

Conditions	Yield
With hydrogenchloride; acetic acid In water at 100℃; for 3h;	98%
With hydrogenchloride; acetic acid In water at 100℃; for 3h;	98%
With hydrogenchloride; acetic acid at 100℃; for 3h;	98%

colchicine (64-86-8) + ethanolamine (141-43-5) → N-[(S)-10-(2-hydroxy-ethylamino)-1,2,3-trimethoxy-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl]-acetamide (55340-40-4)

Conditions	Yield
In dichloromethane at 70℃; for 4h;	98%
In ethanol at 20℃; for 48h;	90%

8-Aminooctanoic acid (1002-57-9) + colchicine (64-86-8) → C29H38N2O7

Conditions	Yield
With sodium hydroxide In ethanol; water for 24h;	96%

colchicine (64-86-8) → C22H25NO6*Li(1+)

Conditions	Yield
With lithium nitrate In methanol at 20℃; for 24h;	96%

colchicine (64-86-8) + sodium thiomethoxide (5188-07-8) → thiocolchicine (2730-71-4)

Conditions	Yield
In water for 1h; Heating;	95%
In methanol; water at 20℃; for 72h;	78%
In methanol; water at 20℃; for 72h;	78%

colchicine (64-86-8) + benzamidin (618-39-3) → (S)-N-(5,6,7,8a-tetrahydro-1,2,3-trimethoxy-10-phenylbenzo[6,7]heptaleno[2,3-d]imidazol-7-yl)acetamide

Conditions	Yield
In benzene at 20℃; for 24h; Condensation; substitution;	95%

colchicine (64-86-8) + 1-(2-aminoethyl)piperidin-3-ol (847499-95-0) → C28H37N3O6 (1415569-00-4)

Conditions	Yield
In dichloromethane at 70℃; for 4h;	95%

colchicine (64-86-8) + ethylenediamine (107-15-3) → (S)-N-(10-((2-aminoethyl)amino)-1,2,3-trimethoxy-9-oxo-5,6,7,9-tetrahydrobenzo [a]heptalen-7-yl acetamide) (67620-27-3)

Conditions	Yield
In dichloromethane at 70℃; for 4h;	95%

colchicine (64-86-8) → C22H25NO6*Rb(1+)*I(1-)

Conditions	Yield
With rubidium iodide In methanol	95%

colchicine (64-86-8) → C22H25NO6*Rb(1+)*ClO4(1-)

Conditions	Yield
With rubidium perchlorate In methanol	95%

colchicine (64-86-8) → C22H25NO6*Na(1+)*NO3(1-)

Conditions	Yield
With sodium nitrate In methanol at 20℃; for 24h;	95%

colchicine (64-86-8) → C22H25NO6*K(1+)*NO3(1-)

Conditions	Yield
With potassium nitrate In methanol at 20℃; for 24h;	95%

colchicine (64-86-8) + benzylamine (100-46-9) → N-<5,6,7,9-tetrahydro-1,2,3-trimethoxy-9-oxo-10-<(phenylmethyl)amino>benzoheptalen-7-yl>-(S)-acetamide (76129-15-2)

Conditions	Yield
In ethanol at 116℃; for 20h;	94%
at 20℃; for 72h;	80%
With ethanol

colchicine (64-86-8) → C22H25NO6*Cs(1+)*I(1-)

Conditions	Yield
With cesium iodide In methanol	94%

colchicine (64-86-8) → C22H25NO6*Mg(2+)*2NO3(1-)

Conditions	Yield
With magnesium(II) nitrate In methanol at 20℃; for 24h;	94%

colchicine (64-86-8) → (aR,5S)-N-(3-hydroxy-2-iodo-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-5-yl)-acetamide (38838-27-6)

Conditions	Yield
Stage #1: colchicine With hydrogenchloride; acetic acid In water at 100℃; for 3h; Stage #2: With iodine; potassium iodide; sodium hydroxide In water at 0 - 5℃; for 1h;	93%
Stage #1: colchicine With hydrogenchloride; acetic acid at 100℃; for 3h; Stage #2: With iodine; potassium iodide; sodium hydroxide In water at 0 - 5℃; for 2h;	91%
Stage #1: colchicine With hydrogenchloride; acetic acid at 100℃; for 3h; Stage #2: With iodine; potassium iodide; sodium hydroxide In water at 0 - 5℃; for 2h;	88%

colchicine (64-86-8) → C22H25NO6*Cs(1+)*ClO4(1-)

Conditions	Yield
With cesium perchlorate In methanol	93%

colchicine (64-86-8) + diethylamine (109-89-7) → N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(diethylamino)-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide (6962-03-4)

Conditions	Yield
In dichloromethane; acetonitrile for 24h; Reflux; regioselective reaction;	92%
In ethanol at 20℃; for 48h;	90%
In methanol at 20℃;	75%

colchicine (64-86-8) → N-(10-amino-1,2,3-trimethoxy-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-acetamide

Conditions	Yield
With ammonium hydroxide Substitution;	90%

colchicine (64-86-8) + di-n-propylamine (142-84-7) → C27H36N2O5

Conditions	Yield
In dichloromethane; acetonitrile for 24h; Reflux; regioselective reaction;	90%

Upstream product

• 4469-06-1 <3-14C>-cinnamic acid 
• 947620-01-1 C₂₈H₃₁N₃O₇ 
• 2103-57-3 2,3,4-trimethoxybenzaldehyde 
• 3476-50-4 deacetylcolchicine 
• 108-24-7 acetic anhydride 
• 133946-40-4 <1-3H>-3-phenylpropanal 
• 186581-53-3 diazomethane 
• 33530-04-0 2,10-didemethylcolchicine 
• 477-27-0 colchiceine 
• 60-29-7 diethyl ether 
• 67-66-3 chloroform 

Downstream Products

• 2730-71-4 thiocolchicine 
• 67620-24-0 10-ethylcolchiceinamide 
• 55511-34-7 N-[(7S)-5,6,7,9-tetrahydro-1,2,3-trimethoxy-10-(ethylthio)-9-oxobenzo[a]heptalen-7-yl]acetamide 
• 2731-31-9 trimethylcolchicinic acid 
• 61014-70-8 (-)-10,11-oxy-10,12a-cyclo-10,11-secocolchicine 
• 2730-82-7 4-Formylcolchicine 
• 7336-33-6 3-demethylcolchicine 
• 518-15-0 colchicide 
• 2826-80-4 N-methyl colchiceinamide 
• 84092-81-9 Hexahydro-colchicin 
• 3986-03-6 1-Hydroxymethyl-colchicin 
• 7336-36-9 2-demethylcolchicine 
• 57866-21-4 2,3-didemethylcolchicine 
• 78231-83-1 1,2-O-didemethylcolchicine 

Relevant articles and documents

SEMISYNTHETIC PROCESS FOR THE PREPARATION OF COLCHICINE

The invention relates to a process for the preparation of colchicine 1 from colchicoside 2 which comprises enzymatic conversion of colchicoside 2 to 3-O- demethylcolchicine 3, wherein the enzyme used is a cellulase. According to another aspect of the invention, 3-O-demethylcolchicine 3 can be converted to colchicine 1 using an alkylating agent. The invention also relates to a process for enriching the colchicine 1 content of extracts from plants belonging to the Colchicaceae family containing colchicine 1, colchicoside 2 and 3 -(9-demethyl colchicine 3, which comprises conversion by means of a colchicoside 2 cellulase to 3-O-demethylcolchicine 3, followed by conversion of 3-O-demethylcolchicine 3 to colchicine 1 using an alkylating agent.

Asymmetric synthesis method of colchicine and allocolchicine

The invention provides an asymmetric synthesis method of colchicine and allocolchicine, and belongs to the field of chemical synthesis. According to the invention, cheap commercial isovanillin A is used as a raw material, asymmetric allyl amination catalyzed by metal Ir is taken as a key reaction, a cyclization precursor E is obtained through Suzuki coupling reaction with a halide D, allocolchicine F is rapidly synthesized through intramolecular oxidative coupling, and finally, efficient asymmetric synthesis of colchicine I is completed through a bionic cyclopropane ring-opening strategy. Thesynthesis strategy used in the invention is simple and economic, good in operability and short in time consumption, and can meet the requirements of new drug development and large-scale preparation.

Synthesis method of colchicine

The invention relates to a synthesis method of colchicine. According to the synthesis method of the colchicine, a compound as shown in the specification is used as a raw material, and then efficient intramolecular [5+2] cycloaddition is considered as key reaction; in combination with locating group guided dehydrogenation Hike reaction and Walker reaction, a molecular skeleton structure is rapidly constructed, so that an obtained structural formula, which has the same structure as a natural product, is the colchicine; and a modification research can be carried out on the colchicine favorably, so as to improve the bioactivity and the toxic and side effects of the colchicine.