2468-21-5

Basic information

• Product Name: Catharanthine
• Synonyms: (+)-3,4-didehydrocoronaridine;18-beta)-lph;catharanthin;ibogamine-18-carboxylicacid,3,4-didehydro-,methylester,(2-alpha,5-beta,6-a;methyl(2-alpha,5-beta,6-alpha,18-beta)-3,4-didehydroibogamine-18-carboxylate;CATHARANTHINE;CATHARANTHINE BASE;methyl (2alpha,5beta,6alpha)-3,4-didehydroibogamine-18beta-carboxylate
• CAS NO: 2468-21-5
• Molecular Formula: C₂₁H₂₄N₂O₂
• Molecular Weight: 336.43
• EINECS: 219-586-6
• Product Categories: Heterocycles;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors
• Mol File: 2468-21-5.mol
• Article Data: 7

Chemical Properties

• Melting Point: 138-1400C
• Boiling Point: 472.9°C (rough estimate)
• Flash Point: 251.1 °C
• Appearance: white to beige/
• Density: 1.1367 (rough estimate)
• Vapor Pressure: 8.33E-10mmHg at 25°C
• Refractive Index: 1.6500 (estimate)
• Storage Temp.: ?20°C
• Solubility: DMSO: soluble5mg/mL (clear solution; warmed)
• PKA: 6.8(at 25℃)
• CAS DataBase Reference: Catharanthine(CAS DataBase Reference)
• NIST Chemistry Reference: Catharanthine(2468-21-5)
• EPA Substance Registry System: Catharanthine(2468-21-5)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 2468-21-5(Hazardous Substances Data)

Usage

Description

Catharanthine, an indole alkaloid analog, is an off-white to pale beige solid. It is known for its potent inhibitory effects on the TRPM8 ion channel and is a precursor to Vinblastine-type alkaloids, which are significant in the pharmaceutical industry.

Uses

Used in Pharmaceutical Industry:
Catharanthine is used as a precursor for Vinblastine-type alkaloids, which are essential in the development of various antineoplastic drugs. These alkaloids play a crucial role in the treatment of different types of cancers due to their ability to disrupt microtubule dynamics, leading to cell cycle arrest and apoptosis.
Used in Anticancer Applications:
Catharanthine is employed as an antineoplastic agent, contributing to the fight against cancer. Its inhibitory action on the TRPM8 ion channel can potentially lead to the development of novel therapeutic strategies for cancer treatment, as TRPM8 is often overexpressed in various cancer types.
Used in Research and Development:
As an inhibitor of TRPM8, Catharanthine is used in research and development for studying the role of TRPM8 in various physiological and pathological processes. Understanding the function of TRPM8 can help in the development of targeted therapies for conditions where TRPM8 plays a significant role, such as pain sensation and cancer progression.

InChI:InChI=1/C21H24N2O2/c1-3-14-10-13-11-21(20(24)25-2)18-16(8-9-23(12-13)19(14)21)15-6-4-5-7-17(15)22-18/h4-7,10,13,19,22H,3,8-9,11-12H2,1-2H3/t13-,19+,21-/m0/s1

Synthetic route

(16R)-5-oxo-catharanthine (105729-49-5) → catharinthine (2468-21-5)

Conditions	Yield
With sodium tetrahydroborate; boron trifluoride diethyl etherate In tetrahydrofuran for 2h; Ambient temperature;	96.2%

indole-3-acetic acid (87-51-4) → catharinthine (2468-21-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: triethylamine / dimethylformamide / 0.33 h / -10 - -5 °C 2: triethylamine / dimethylformamide / 24 h 3: 29.5 percent / NaBH4, tributyltin chloride / methanol / Irradiation 4: 96.2 percent / NaBH4, boron trifluoride etherate / tetrahydrofuran / 2 h / Ambient temperature View Scheme

C15H17NO3 (125213-31-2) → catharinthine (2468-21-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dimethylformamide / 24 h 2: 29.5 percent / NaBH4, tributyltin chloride / methanol / Irradiation 3: 96.2 percent / NaBH4, boron trifluoride etherate / tetrahydrofuran / 2 h / Ambient temperature View Scheme

(-)-2-(1-<2-(indol-3-yl)-1-oxo-ethyl>)-6-ethyl-7-exo-chloro-2-azabicyclo<2.2.2>oct-5-ene-7-endo-carboxylic acid methyl ester (129030-48-4) → catharinthine (2468-21-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 29.5 percent / NaBH4, tributyltin chloride / methanol / Irradiation 2: 96.2 percent / NaBH4, boron trifluoride etherate / tetrahydrofuran / 2 h / Ambient temperature View Scheme

stemmadenine acetate → catharinthine (2468-21-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: T. iboga precondylocarpine acetate synthase 1; FAD / aq. buffer / 2 h / 37 °C / pH 9.5 / Enzymatic reaction 2: NADPH / aq. buffer / 1 h / 37 °C / pH 9.5 / Enzymatic reaction 3: NADPH / aq. buffer / pH 9.5 / Enzymatic reaction View Scheme

C23H27N2O4(1+) → catharinthine (2468-21-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: NADPH / aq. buffer / 1 h / 37 °C / pH 9.5 / Enzymatic reaction 2: NADPH / aq. buffer / pH 9.5 / Enzymatic reaction View Scheme

dehydrosecodine → catharinthine (2468-21-5)

Conditions	Yield
With NADPH In aq. buffer pH=9.5; Enzymatic reaction;

catharinthine (2468-21-5) → (+)-dihydrocatharanthine (38542-83-5)

Conditions	Yield
With platinum(IV) oxide; hydrogen In methanol under 760.051 Torr; for 0.0833333h; Inert atmosphere;	93%

catharinthine (2468-21-5) + vindoline (2182-14-1) → anhydrovinblastine (38390-45-3, 56083-20-6, 61246-76-2, 105815-31-4)

Conditions	Yield
Stage #1: catharinthine; vindoline With iron(III) chloride hexahydrate at 25℃; Stage #2: With sodium tetrahydroborate at 0℃;	90%
With sodium tetrahydroborate; iron(III) chloride 1.) buffer; Yield given. Multistep reaction;
With hydrogenchloride; iron(III) chloride In 2,2,2-trifluoroethanol; water at 25℃; for 2h; Inert atmosphere;

catharinthine (2468-21-5) + methyl chloroformate (79-22-1) → N-(methoxycarbonyl)catharanthine (60706-87-8)

Conditions	Yield
Stage #1: catharinthine With potassium hydride In tetrahydrofuran at 0℃; Stage #2: methyl chloroformate In tetrahydrofuran at 0 - 23℃; for 15h;	90%
Stage #1: catharinthine With potassium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: methyl chloroformate In tetrahydrofuran at 0 - 20℃; for 19h; Inert atmosphere;	86%
Stage #1: catharinthine With potassium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: methyl chloroformate In tetrahydrofuran at 0 - 20℃; for 19h; Inert atmosphere;	86%

trimethylsilyl cyanide (7677-24-9) + catharinthine (2468-21-5) → (4S,7R,9S)-methyl 4-cyano-5-ethyl-2,4,7,8,9,10-hexahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indole-9-carboxylate (136118-90-6)

Conditions	Yield
With 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione In methanol UV-irradiation;	88%
With eosin B disodium salt In methanol for 2h; Irradiation; Yield given;
With eosin B disodium salt In methanol for 2h; Irradiation; other photooxidants (without O2);
With [Ir(C6H2F2-C5H3NCF3)2(4,4′-di-tert-butyl-2,2′-dipyridyl)]+ In methanol for 0.0333333h; Reagent/catalyst; Inert atmosphere; Irradiation; Flow reactor;	96 %Spectr.

(-)-vindoline + catharinthine (2468-21-5) → (+)-anhydrovinblastine

Conditions	Yield
Stage #1: (-)-vindoline; catharinthine With iron(III) chloride In hydrogenchloride; 2,2,2-trifluoroethanol; water at 23℃; for 2h; Stage #2: With oxygen; ferric citrate In hydrogenchloride; 2,2,2-trifluoroethanol; water Stage #3: With sodium tetrahydroborate In hydrogenchloride; 2,2,2-trifluoroethanol; water at 0℃; for 0.5h;	87%

catharinthine (2468-21-5) → C19H22N2 (1674-00-6)

Conditions	Yield
Stage #1: catharinthine With sodium hydroxide In ethanol at 70℃; for 16h; Stage #2: With hydrogenchloride In ethanol; water at 70℃;	85%
Stage #1: catharinthine With water; sodium hydroxide In ethanol at 70℃; for 16h; Stage #2: With hydrogenchloride In ethanol at 70℃;	85%

catharinthine (2468-21-5) + vindoline (2182-14-1) → 3',4'-anhydrovinblastine (38390-45-3, 56083-20-6, 61246-76-2, 105815-31-4)

Conditions	Yield
Stage #1: catharinthine With hydrogenchloride In water aq. buffer; Stage #2: vindoline With iron(III) chloride In water at 20℃; for 18h; Stage #3: With sodium tetrahydroborate; ammonia In water at 20℃; for 0.166667h;	80%

4-desacetoxy-6,7-dihydrovindoline + catharinthine (2468-21-5) → C44H56N4O6

Conditions	Yield
Stage #1: 4-desacetoxy-6,7-dihydrovindoline; catharinthine With iron(III) chloride In hydrogenchloride; 2,2,2-trifluoroethanol; water at 25℃; for 2h; Stage #2: With sodium tetrahydroborate In hydrogenchloride; 2,2,2-trifluoroethanol; water	77%

catharinthine (2468-21-5) → C20H24N2O

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 0.166667h;	77%
Stage #1: catharinthine With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: With water; ammonium chloride In tetrahydrofuran	77%

catharinthine (2468-21-5) + vindoline (2182-14-1) → C46H57N7O8

Conditions	Yield
Stage #1: catharinthine; vindoline With hydrogenchloride; iron(III) chloride In 2,2,2-trifluoroethanol; water at 25℃; Stage #2: With sodium tetrahydroborate; cesium azide; ferric oxalate at 0℃; for 0.5h;	75%

catharinthine (2468-21-5) → isocatharanthine (1142118-65-7)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol under 225.023 Torr; for 2h;	73%

trimethylsilyl cyanide (7677-24-9) + catharinthine (2468-21-5) → 3β-cyano-7β-hydroxyindolenine catharanthine

Conditions	Yield
With oxygen; 5,15,10,20-tetraphenylporphyrin In dichloromethane Irradiation;	72%

catharinthine (2468-21-5) → C20H22N2O2 (63944-54-7)

Conditions	Yield
Stage #1: catharinthine With sodium hydroxide In ethanol at 70℃; for 16h; Stage #2: With hydrogenchloride In ethanol; water at 0℃;	70%
Stage #1: catharinthine With water; sodium hydroxide In ethanol at 70℃; for 16h; Stage #2: With hydrogenchloride In ethanol	70%
With potassium hydroxide In ethanol for 8h; Heating;

trimethylsilyl cyanide (7677-24-9) + catharinthine (2468-21-5) → 3-cyanocatharanthine (132019-29-5) + 21-cyanocatharanthine (82622-21-7)

Conditions	Yield
With lithium perchlorate In benzene	A 3% B 68%

(-)-vindoline + catharinthine (2468-21-5) → (+)-anhydrovinblastine + (+)-leurosidine + (+)-vinblastine

Conditions	Yield
Stage #1: (-)-vindoline; catharinthine With iron(III) chloride In hydrogenchloride; 2,2,2-trifluoroethanol; water at 23℃; for 2h; Stage #2: With oxygen; ferric nitrate In hydrogenchloride; 2,2,2-trifluoroethanol; water Stage #3: With sodium tetrahydroborate In hydrogenchloride; 2,2,2-trifluoroethanol; water at 0℃; for 0.5h;	A 63% B 17% C 10%
Stage #1: (-)-vindoline; catharinthine With iron(III) chloride In hydrogenchloride; 2,2,2-trifluoroethanol; water at 23℃; for 2h; Stage #2: With iron(III) sulfate; oxygen In hydrogenchloride; 2,2,2-trifluoroethanol; water Stage #3: With sodium tetrahydroborate In hydrogenchloride; 2,2,2-trifluoroethanol; water at 0℃; for 0.5h;	A 33% B 22% C 39%

catharinthine (2468-21-5) → 10-iodocatharanthine (90012-96-7)

Conditions	Yield
With N-iodo-succinimide; trifluoroacetic acid In dichloromethane at -40℃; for 2h;	55%

sodium ethanolate (141-52-6) + catharinthine (2468-21-5) → C22H26N2O2 (1257634-10-8)

Conditions	Yield
In ethanol at 20℃; for 16h;	49%

ethanol (64-17-5) + sodium ethanolate (141-52-6) + catharinthine (2468-21-5) → C22H26N2O2 (1257634-10-8)

Conditions	Yield
at 20℃; for 16h;	49%

catharinthine (2468-21-5) → 10-nitrocatharanthine (1328885-33-1)

Conditions	Yield
With nitric acid In chloroform; acetic acid at -20℃;	45%

catharinthine (2468-21-5) → C20H22N2O (1257634-12-0)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃;	37%
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 0.0833333h;	37%

methanol (67-56-1) + catharinthine (2468-21-5) → C23H30N2O4 (132019-27-3)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone at -5 - 0℃; for 0.333333h; oxidative fragmentation by DDQ, other reactant, other reagent, other solvent;	35%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone at -5 - 0℃; for 0.333333h;	35%

potassium cyanide (151-50-8) + catharinthine (2468-21-5) → 21-cyanocatharanthine (82622-21-7) + C22H21N3O2 (132019-33-1) + C22H23N3O2 (132019-31-9)

Conditions	Yield
With 18-crown-6 ether; 2,3-dicyano-5,6-dichloro-p-benzoquinone 1) benzene, 25 deg C, 30 min; Yield given. Multistep reaction;	A 30% B n/a C n/a
With 18-crown-6 ether; 2,3-dicyano-5,6-dichloro-p-benzoquinone 1) benzene, 25 deg C, 30 min; Yield given. Multistep reaction. Yields of byproduct given;

catharinthine (2468-21-5) → 3-cyanocatharanthine (132019-29-5) + 2-((Z)-2-Formyl-but-1-enyl)-2,3,6,11-tetrahydro-1H,5H-indolizino[8,7-b]indole-11b-carboxylic acid methyl ester (132019-28-4)

Conditions	Yield
With water; 2,3-dicyano-5,6-dichloro-p-benzoquinone In tetrahydrofuran	A 10% B 30%

C23H30N2O3 + catharinthine (2468-21-5) → C44H54N4O5

Conditions	Yield
Stage #1: C23H30N2O3; catharinthine With Trametes versicolor laccase; oxygen at 30℃; for 24h; pH=4.5; aq. acetate buffer; Stage #2: With sodium hydroxide; sodium tetrahydroborate aq. acetate buffer;	21%

potassium cyanide (151-50-8) + catharinthine (2468-21-5) → 3-cyanocatharanthine (132019-29-5) + C22H21N3O3 (132019-34-2)

Conditions	Yield
With 18-crown-6 ether; 2,3-dicyano-5,6-dichloro-p-benzoquinone 1. THF; Multistep reaction;	A 20% B n/a
With 18-crown-6 ether; 2,3-dicyano-5,6-dichloro-p-benzoquinone 1) THF; Yield given. Multistep reaction;

trimethylsilyl cyanide (7677-24-9) + catharinthine (2468-21-5) → 3β-cyanocatharanthine (300535-95-9)

Conditions	Yield
With beta-carotene; oxygen; 5,15,10,20-tetraphenylporphyrin In dichloromethane for 4h; Irradiation;	20%

trimethylsilyl cyanide (7677-24-9) + catharinthine (2468-21-5) → 5-cyanocatharanthine (132019-30-8) + 3-cyanocatharanthine (132019-29-5) + 21-cyanocatharanthine (82622-21-7)

Conditions	Yield
With lithium perchlorate In tetrahydrofuran	A 10% B 18% C 16%

catharinthine (2468-21-5) → 10-bromocatharanthine (1328885-35-3)

Conditions	Yield
With N-Bromosuccinimide; trifluoroacetic acid In dichloromethane at -40℃; for 2h;	18%

catharinthine (2468-21-5) + 11-methoxytabersonine (27773-39-3, 86116-70-3, 106356-44-9) → C43H50N4O5

Conditions	Yield
	4%

Upstream product

• 105729-49-5 (16R)-5-oxo-catharanthine 
• 87-51-4 indole-3-acetic acid 
• 125213-31-2 C₁₅H₁₇NO₃ 
• 129030-48-4 (-)-2-(1-<2-(indol-3-yl)-1-oxo-ethyl>)-6-ethyl-7-exo-chloro-2-azabicyclo<2.2.2>oct-5-ene-7-endo-carboxylic acid methyl ester 
• 77794-83-3 Δ⁵-catharanthine 
• 300535-95-9 (+)-3β-Cyanocatharanthine 

Downstream Products

• 140156-61-2 C₂₁H₂₄N₂O₃*C₇H₅ClO₂ 
• 38390-45-3 anhydrovinblastine 
• 23360-92-1 vinleurosine 
• 1355-31-3 catharine 
• 35478-77-4 16α-(methoxycarbonyl)cleavamine 
• 20643-72-5 16-carbomethoxycleavamine 
• 854756-74-4 10'-thiomethylvinblastine 
• 1328885-60-4 10'-methylthioleurosidine 
• 1043910-92-4 C₅₃H₆₃N₅O₇ 
• 1043910-81-1 C₅₂H₆₁N₅O₇ 
• 1043910-82-2 C₅₃H₆₃N₅O₇ 
• 1043910-83-3 C₅₂H₆₀FN₅O₇ 
• 1043910-91-3 C₅₃H₆₃N₅O₈ 
• 1043910-90-2 C₅₃H₆₃N₅O₈ 

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