3486-66-6

Basic information

• Product Name: COPTISINE
• Synonyms: COPTISINE;Coptisin;5,6-Dihydro-2,3:9,10-bis(methylenedioxy)dibenzo[a,g]quinolizinium;6,7-Dihydrobis[1,3]benzodioxolo[5,6-a:4',5'-g]quinolizinium;Coptisine Sulfate;COPTISINE(P);Bis[1,3]benzodioxolo[5,6-a:4',5'-g]quinolizinium,6,7-dihydro-;Coptisine, 98%, from Coptis chinensis Franch.
• CAS NO: 3486-66-6
• Molecular Formula: C₁₉H₁₄NO₄
• Molecular Weight: 320.32
• Product Categories: Alkaloids;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract
• Mol File: 3486-66-6.mol
• Article Data: 5

Chemical Properties

• Melting Point: 212-217 °C
• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: g/cm³
• CAS DataBase Reference: COPTISINE(CAS DataBase Reference)
• NIST Chemistry Reference: COPTISINE(3486-66-6)
• EPA Substance Registry System: COPTISINE(3486-66-6)

Safety Data

• Hazard Codes: A poison.:
• Safety Statements: A poison by ingestion. When heated to decomposition it emits toxic vapors of NO:
• Hazardous Substances Data: 3486-66-6(Hazardous Substances Data)

Usage

Definition

ChEBI: A natural product found in Coptis japonica.

Hazard

A poison.

Safety Profile

A poison by ingestion. When heated to decomposition it emits toxic vapors of NOx.

Synthetic route

C19H15NO5 → coptisine (3486-66-6)

Conditions	Yield
With methanesulfonyl chloride; triethylamine In dichloromethane at 20℃; for 6h;	74%

berberine (2086-83-1) → coptisine (3486-66-6)

Conditions	Yield
Multistep reaction;

dichloromethane (75-09-2) + 2,3,9,10-tetrahydroxy-protoberberine chloride → coptisine (3486-66-6)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 40 - 90℃; for 5h; Inert atmosphere;

protopine (130-86-9) → coptisine (3486-66-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: oxalyl dichloride / chloroform / 1 h / Reflux 2: dimethyl sulfoxide / 25.5 h / 115 - 120 °C View Scheme

N-Methyl-dihydrocoptisinium-Kation (20105-28-6) → coptisine (3486-66-6)

Conditions	Yield
In dimethyl sulfoxide at 115 - 120℃; for 25.5h;

Dihydrocoptisine (53777-78-9) → coptisine (3486-66-6)

Conditions	Yield
With iodine; potassium acetate In ethanol at 20℃; Inert atmosphere;	5.5 mg

5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline (94143-83-6) → coptisine (3486-66-6)

Conditions

Yield

Multi-step reaction with 7 steps 1: copper(l) iodide; benzoic acid / toluene / 12 h / 80 °C / Inert atmosphere; Molecular sieve 2: potassium carbonate / methanol / 0.5 h / 20 °C / Inert atmosphere 3: sodium formate; tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide; water / 1 h / 100 °C / Inert atmosphere 4: tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide / acetonitrile / 2 h / 50 °C / Inert atmosphere; Molecular sieve 5: Wilkinson's catalyst; diphenyl phosphoryl azide / diethylene glycol dimethyl ether / 12 h / 160 °C / Inert atmosphere 6: lithium aluminium tetrahydride; aluminum (III) chloride / diethyl ether / 2 h / Reflux; Inert atmosphere 7: potassium acetate; iodine / ethanol / 20 °C / Inert atmosphere View Scheme

C20H16BrNO4 → coptisine (3486-66-6)

Conditions

Yield

Multi-step reaction with 5 steps 1: sodium formate; tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide; water / 1 h / 100 °C / Inert atmosphere 2: tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide / acetonitrile / 2 h / 50 °C / Inert atmosphere; Molecular sieve 3: Wilkinson's catalyst; diphenyl phosphoryl azide / diethylene glycol dimethyl ether / 12 h / 160 °C / Inert atmosphere 4: lithium aluminium tetrahydride; aluminum (III) chloride / diethyl ether / 2 h / Reflux; Inert atmosphere 5: potassium acetate; iodine / ethanol / 20 °C / Inert atmosphere View Scheme

5-bromo-benzo[1,3]dioxole-4-carbaldehyde (72744-54-8) → coptisine (3486-66-6)

Conditions

Yield

Multi-step reaction with 7 steps 1: copper(l) iodide; benzoic acid / toluene / 12 h / 80 °C / Inert atmosphere; Molecular sieve 2: potassium carbonate / methanol / 0.5 h / 20 °C / Inert atmosphere 3: sodium formate; tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide; water / 1 h / 100 °C / Inert atmosphere 4: tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide / acetonitrile / 2 h / 50 °C / Inert atmosphere; Molecular sieve 5: Wilkinson's catalyst; diphenyl phosphoryl azide / diethylene glycol dimethyl ether / 12 h / 160 °C / Inert atmosphere 6: lithium aluminium tetrahydride; aluminum (III) chloride / diethyl ether / 2 h / Reflux; Inert atmosphere 7: potassium acetate; iodine / ethanol / 20 °C / Inert atmosphere View Scheme

C20H17NO4 → coptisine (3486-66-6)

Conditions

Yield

Multi-step reaction with 4 steps 1: tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide / acetonitrile / 2 h / 50 °C / Inert atmosphere; Molecular sieve 2: Wilkinson's catalyst; diphenyl phosphoryl azide / diethylene glycol dimethyl ether / 12 h / 160 °C / Inert atmosphere 3: lithium aluminium tetrahydride; aluminum (III) chloride / diethyl ether / 2 h / Reflux; Inert atmosphere 4: potassium acetate; iodine / ethanol / 20 °C / Inert atmosphere View Scheme

C23H24BrNO4Si → coptisine (3486-66-6)

Conditions

Yield

Multi-step reaction with 6 steps 1: potassium carbonate / methanol / 0.5 h / 20 °C / Inert atmosphere 2: sodium formate; tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide; water / 1 h / 100 °C / Inert atmosphere 3: tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide / acetonitrile / 2 h / 50 °C / Inert atmosphere; Molecular sieve 4: Wilkinson's catalyst; diphenyl phosphoryl azide / diethylene glycol dimethyl ether / 12 h / 160 °C / Inert atmosphere 5: lithium aluminium tetrahydride; aluminum (III) chloride / diethyl ether / 2 h / Reflux; Inert atmosphere 6: potassium acetate; iodine / ethanol / 20 °C / Inert atmosphere View Scheme

13-carboxaldehyde-8-oxocoptisine → coptisine (3486-66-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: Wilkinson's catalyst; diphenyl phosphoryl azide / diethylene glycol dimethyl ether / 12 h / 160 °C / Inert atmosphere 2: lithium aluminium tetrahydride; aluminum (III) chloride / diethyl ether / 2 h / Reflux; Inert atmosphere 3: potassium acetate; iodine / ethanol / 20 °C / Inert atmosphere View Scheme

coptisinone (19716-61-1) → coptisine (3486-66-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride; aluminum (III) chloride / diethyl ether / 2 h / Reflux; Inert atmosphere 2: potassium acetate; iodine / ethanol / 20 °C / Inert atmosphere View Scheme

C9H6ClNO2 → coptisine (3486-66-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / dimethyl sulfoxide / 90 °C / Inert atmosphere 2: sodium carbonate; tris-(dibenzylideneacetone)dipalladium(0); XPhos / toluene; ethanol / 12 h / 110 °C / Inert atmosphere 3: triethylamine; methanesulfonyl chloride / dichloromethane / 6 h / 20 °C View Scheme

7-chloro-[1,3]dioxolo[4,5-h]isoquinoline → coptisine (3486-66-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate; tris-(dibenzylideneacetone)dipalladium(0); XPhos / toluene; ethanol / 12 h / 110 °C / Inert atmosphere 2: triethylamine; methanesulfonyl chloride / dichloromethane / 6 h / 20 °C View Scheme

C10H8ClNO2 → coptisine (3486-66-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: boron tribromide / dichloromethane / 2 h / -78 - -30 °C / Inert atmosphere 2: potassium carbonate / dimethyl sulfoxide / 90 °C / Inert atmosphere 3: sodium carbonate; tris-(dibenzylideneacetone)dipalladium(0); XPhos / toluene; ethanol / 12 h / 110 °C / Inert atmosphere 4: triethylamine; methanesulfonyl chloride / dichloromethane / 6 h / 20 °C View Scheme

coptisine (3486-66-6) + acetone (67-64-1) → (±)-8-acetonyldihydrocoptisine

Conditions	Yield
With sodium hydroxide at 20℃; for 1h;	69.8%

coptisine (3486-66-6) → C19H13NO5 (84229-86-7)

coptisine (3486-66-6) + dimethyl sulfate (77-78-1) → C20H18NO4(1+)*CH3O4S(1-) (107651-12-7)

Conditions	Yield
With lithium aluminium tetrahydride 1.) THF; 2.) benzene; Yield given. Multistep reaction;

coptisine (3486-66-6) → C20H15NO5 (107651-13-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) LiAlH4 / 1.) THF; 2.) benzene 2: 1.) 25percent KOH; 2.) m-chloroperoxybenzoic acid / 1.) MeOH; 2.) CH2Cl2 View Scheme

coptisine (3486-66-6) → (6S,7S)-8-Methyl-7-(6-vinyl-benzo[1,3]dioxol-5-yl)-6,7,8,9-tetrahydro-[1,3]dioxolo[4,5-h]isoquinolin-6-ol (107651-14-9, 107651-15-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) LiAlH4 / 1.) THF; 2.) benzene 2: 1.) 25percent KOH; 2.) m-chloroperoxybenzoic acid / 1.) MeOH; 2.) CH2Cl2 3: 80 percent / sodium borohydride / methanol / Heating View Scheme

coptisine (3486-66-6) → (6R,7S)-8-Methyl-7-(6-vinyl-benzo[1,3]dioxol-5-yl)-6,7,8,9-tetrahydro-[1,3]dioxolo[4,5-h]isoquinolin-6-ol (107651-14-9, 107651-15-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) LiAlH4 / 1.) THF; 2.) benzene 2: 1.) 25percent KOH; 2.) m-chloroperoxybenzoic acid / 1.) MeOH; 2.) CH2Cl2 3: 15 percent / sodium borohydride / methanol / Heating View Scheme

coptisine (3486-66-6) → 7,8,6',8'-tetrahydro-6H-(7'rN)-spiro[[1,3]dioxolo[4,5-g]isoquinoline-5,7'-indeno[4,5-d][1,3]dioxole]-6't,8'c-diol (84229-91-4)

Conditions	Yield
Multi-step reaction with 4 steps 2: 64 percent / LiAlH(OtBu)3 / tetrahydrofuran; diethyl ether / Heating 3: 67 percent / Heating 4: 74 percent / aq. KOH; dioxane / 48 h / Heating View Scheme

coptisine (3486-66-6) → (+/-)-ochrobirine (24181-64-4, 33805-02-6, 68736-95-8, 76231-96-4, 99265-30-2, 126187-21-1)

Conditions	Yield
Multi-step reaction with 4 steps 2: 61 percent 3: 89 percent / AgOAc 4: LiAlH4 View Scheme
Multi-step reaction with 5 steps 2: 64 percent / LiAlH(OtBu)3 / tetrahydrofuran; diethyl ether / Heating 3: 67 percent / Heating 4: 74 percent / aq. KOH; dioxane / 48 h / Heating 5: 73 percent / tetrahydrofuran / Ambient temperature View Scheme

coptisine (3486-66-6) → C20H13NO7

Conditions	Yield
Multi-step reaction with 3 steps 2: 61 percent 3: 89 percent / AgOAc View Scheme

coptisine (3486-66-6) → C20H15NO7 (84229-89-0)

Conditions	Yield
Multi-step reaction with 3 steps 2: 64 percent / LiAlH(OtBu)3 / tetrahydrofuran; diethyl ether / Heating 3: 67 percent / Heating View Scheme

coptisine (3486-66-6) → C22H18ClNO7

Conditions	Yield
Multi-step reaction with 2 steps 2: 61 percent View Scheme

coptisine (3486-66-6) → C19H15NO5 (84229-87-8, 84277-21-4)

Conditions	Yield
Multi-step reaction with 2 steps 2: 20 percent / LiAlH(OtBu)3 / tetrahydrofuran; diethyl ether / Heating View Scheme

coptisine (3486-66-6) → C19H15NO5 (84229-87-8, 84277-21-4)

Conditions	Yield
Multi-step reaction with 2 steps 2: 64 percent / LiAlH(OtBu)3 / tetrahydrofuran; diethyl ether / Heating View Scheme

coptisine (3486-66-6) → C20H19NO6 (24181-64-4, 33805-02-6, 68736-95-8, 76231-96-4, 99265-30-2, 126187-21-1)

Conditions	Yield
Multi-step reaction with 4 steps 2: 61 percent 3: 89 percent / AgOAc 4: LiAlH4 View Scheme

coptisine (3486-66-6) → 13-nitro-8-oxocoptisine (1427306-71-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / 8 h / 80 °C 2: nitric acid / dichloromethane / 0.5 h / 20 - 30 °C / Reflux; Inert atmosphere View Scheme

coptisine (3486-66-6) → 12,13-dinitro-8-oxocoptisine (1427306-72-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / 8 h / 80 °C 2: nitric acid / dichloromethane / 20 °C / Inert atmosphere View Scheme

coptisine (3486-66-6) → 1,2-methylenedioxy-9,10-dihydroxyl-12-sulfonyl-8-oxoprotoberberine (1427306-73-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / 8 h / 80 °C 2: sulfuryl dichloride / dichloromethane / 2 h / 0 °C / Inert atmosphere View Scheme

coptisine (3486-66-6) → 8-thiocoptisine (1427306-74-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / 8 h / 80 °C 2: tetraphosphorus decasulfide / pyridine; dichloromethane / 3 h / Reflux; Inert atmosphere View Scheme

coptisine (3486-66-6) → 13-bromo-8-thiocoptisine (1427306-75-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydroxide / 8 h / 80 °C 2: N-Bromosuccinimide / chloroform / 24 h / 20 °C / Reflux; Inert atmosphere 3: tetraphosphorus decasulfide / pyridine; dichloromethane / 3 h / Reflux; Inert atmosphere View Scheme

coptisine (3486-66-6) → 13-nitro-8-thiocoptisine (1427306-76-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydroxide / 8 h / 80 °C 2: nitric acid / dichloromethane / 0.5 h / 20 - 30 °C / Reflux; Inert atmosphere 3: tetraphosphorus decasulfide / pyridine; dichloromethane / 3 h / Reflux; Inert atmosphere View Scheme

coptisine (3486-66-6) → 12,13-dinitro-8-thiocoptisine (1427306-77-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydroxide / 8 h / 80 °C 2: nitric acid / dichloromethane / 20 °C / Inert atmosphere 3: tetraphosphorus decasulfide / pyridine; dichloromethane / 3 h / Reflux; Inert atmosphere View Scheme

coptisine (3486-66-6) → 13-bromo-8-oxocoptisine (1427306-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / 8 h / 80 °C 2: N-Bromosuccinimide / chloroform / 24 h / 20 °C / Reflux; Inert atmosphere View Scheme

coptisine (3486-66-6) → coptisinone (19716-61-1)

Conditions	Yield
With potassium hydroxide at 80℃; for 8h;	28 mg
With sodium hydroxide; potassium hexacyanoferrate(III) In water Reflux;

coptisine (3486-66-6) + ethyl iodide (75-03-6) → 2,3,9,10-tetraethoxy-8-oxoprotoberberine (1427306-68-0)

Conditions	Yield
With potassium hydroxide at 80℃; for 8h; Inert atmosphere;	39 mg

coptisine (3486-66-6) + 1-iodo-propane (107-08-4) → 2,3,9,10-tetrapropoxy-8-oxoprotoberberine (1427306-69-1)

Conditions	Yield
at 80℃; for 8h; Inert atmosphere;	36 mg

coptisine (3486-66-6) + 1,2-dichloro-ethane (107-06-2) → 2,3-ethylenedioxy-9,10-ethylenedioxy-8-oxoprotoberbeirine (1427306-67-9)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 80℃; for 8h; Inert atmosphere;	33 mg

Upstream product

• 19716-61-1 coptisinone 
• 72744-54-8 5-bromo-benzo[1,3]dioxole-4-carbaldehyde 
• 94143-83-6 5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline 
• 53777-78-9 Dihydrocoptisine 
• 20105-28-6 N-Methyl-dihydrocoptisinium-Kation 
• 130-86-9 protopine 
• 75-09-2 dichloromethane 
• 2086-83-1 berberine 

Downstream Products

• 19716-61-1 coptisinone 
• 84-39-9 Stylopine 
• 24181-64-4 C₂₀H₁₉NO₆ 
• 24181-64-4 (+/-)-Ochrobirin 

Relevant articles and documents

Method for synthesizing benzophenanthridine and protoberberine alkaloids through modular diversity regulation and control

The invention discloses a method for synthesizing benzophenanthridine and protoberberine alkaloids through modular diversity regulation and control. The method comprises the following steps: improving a substituent group of a high-iodine salt leaving group, generating pyridine alkyne under the action of relatively mild potassium tert-butoxide, and carrying out [4 + 2] cycloaddition reaction on the pyridine alkyne and diene to obtain polysubstituted isoquinoline ring precursor compounds. Ring opening and aromatization of the isoquinoline ring precursor are realized by developing a novel iridium-catalyzed cross-coupling method, polysubstituted isoquinoline ring compounds with connecting capacity are efficiently synthesized, and then the polysubstituted isoquinoline ring compounds are coupled with a high-activity polysubstituted cyclic boric acid to obtain 3-aryl isoquinoline high-grade intermediates. Through application of two different chemical principles, regulation and control of the 3-aryl isoquinoline high-grade intermediates are realized, and benzophenanthridine and protoberberine alkaloids are modularly, diversely and efficiently synthesized.

Facile synthesis of tetrahydroprotoberberine and protoberberine alkaloids from protopines and study on their antibacterial activities

A series of isoquinoline alkaloids including tetrahydroprotoberberines, N-methyl tetrahydroprotoberberines and protoberberines were facile synthesised with protopines as the starting material. All compounds were evaluated for their antibacterial activities against four pathogenic bacteria Escherichia coli, Staphyloccocus aureus, Staphylococcus gallinarum and Salmonella choleraesuis. Experimental results indicated that protoberberines were the most active compounds to the target bacteria among the tested alkaloids. It was suggested that planar molecule with high aromatisation level (e.g. coptisine 5 and berberine 6) or a positive charge of the molecules (e.g. N-methyl tetrahydroprotoberberines 11 and 12) had a positive influence on the antibacterial effects.

TRANSFORMATION OF PROTOBERBERINES INTO SPIROBENZYLISOQUINOLINES. STEREOSELECTIVE CONVERSION OF COPTISINE INTO (+/-)-OCHROBIRINE

Reduction of the 8,14-cycloberbin-13-one (7a), derived from coptisine, (6a), with LiAlH(OBut)3 gave stereoselectively the alcohol (8a) which was subsequently treated with ethyl chloroformate to afford the oxazolidinone (10a).Hydrolysis of 10a followed by methylation with methyl iodide provided (+/-)-ochrobirine (1a).KEYWORDS - ochrobirine, spirobenzylisoquinoline alkaloid; coptisine; berberine; protoberberine alkaloid; stereoselective reduction; ethyl chloroformate; regioselectivce C8-N bond cleavage; stereoselective transformation