128-62-1

Basic information

• Product Name: Narcotine
• Synonyms: ,2,3,4-tetrahydroisoquinaline;[S-(R*,S*)]-6,7-Dimethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl)-1(3H)-Isobenzofuranone;1(3H)-Isobenzofuranone, 6,7-dimethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl)-, [S-(R*,S*)]-;1-alpha-Narcotine;5-g)isoquinolin-5-yl)-,(s-(r*,s*))-3-dioxolo(4;5-g]isoquinolin-5-yl)-,[s-(theta,s)]-3-dioxolo[4;6,7-Dimethoxy-3-(4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-2-benzofuran-1(3H)-one;6,7-dimethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-1(3h)-isobenzofuranon
• CAS NO: 128-62-1
• Molecular Formula: C₂₂H₂₃NO₇
• Molecular Weight: 413.42
• EINECS: 204-899-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Asymmetric Synthesis;Chiral Building Blocks;Complex Molecules;FINACEAE
• Mol File: 128-62-1.mol
• Article Data: 14

Chemical Properties

• Melting Point: 174-176 °C(lit.)
• Boiling Point: 532.6°C (rough estimate)
• Flash Point: 295.692 °C
• Appearance: Crystalline solid
• Density: 1.395
• Vapor Pressure: 4.83E-14mmHg at 25°C
• Refractive Index: 1.5614 (estimate)
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Practically insoluble in water, soluble in acetone, slightly soluble in ethanol (96 per cent). It dissolves in strong acids; on dilution of the solution with water, the base may be precipitated.
• PKA: 7.8(at 25℃)
• Water Solubility: 302.9mg/L(25 oC)
• Merck: 13,6752
• CAS DataBase Reference: Narcotine(CAS DataBase Reference)
• NIST Chemistry Reference: Narcotine(128-62-1)
• EPA Substance Registry System: Narcotine(128-62-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 24/25
• RIDADR: 1544
• WGK Germany: 3
• RTECS: RD2625000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 128-62-1(Hazardous Substances Data)

Usage

Description

A major constituent of opium (Papaver sornni!erurn), this phthalideisolquinoline base was probably first discovered by Derosne, but initially characterized by Robiquet who gave it the formula C23H3S0 7N, changed to that now accepted by Matthiesen and Foster. It crystallizes in colourless needles from EtOH and has [α]D - 198° (c 1.0, CHC13); - 146° (c 2.0, toluene); - 147° (c 1.59, C6H6) and + 50° (1 % HCl). The alkaloid is a weak, monoacidic, tertiary base, forming unstable salts with acids which are dissociated with H20. The hydrochloride crystallizes with varying amounts of H20, is very soluble in water, readily decomposing into basic salts on standing. The platinichloride is amorphous; the oxalate has m.p. 174°C;[α]20D + 39.5° (H20); the phthalate, m.p. 160°C; [α]22D + 115° (CHC13); sesquisulphate, colourless crystals of the hexahydrate and the picrate, m.p. 1 74-S°C. The (+)-bromocamphorsulphonate has m.p. 110- 120°C; [α]D + 100.7° (CHC13) and the corresponding (-)-bromocamphorsul_x0002_phonate, m.p. l80.SoC; [α]D + 29° (CHC13). The alkaloid yields an N-oxide which is a hygroscopic solid; [α]D + 135° (CHC13) furnishing a crystalline hydrochloride, m.p. 193°C; platinichloride, m.p. 175°C and a picrate, m.p. 130°C.The base is unstable to heat and when heated in a sealed tube yields a mixture of dimethylnornarcotine, methylnornarcotine and nornarcotine. On heating with H20 and 150°C, or on boiling with dilute acids, it is hydrolyzed to opianic acid and hydrocotarnine. Similar degradations are brought about by acid oxidation orreduction, e.g. Zn and dilute HCl gives hydrocotarnine and meconin while dilute HN03 yields cotarnine and opianic acid. Pharmacologically, narcotine resembles thebaine (q.v.) in its action, being a reflex stimulant rather than a narcotic.

Chemical Properties

Crystalline Solid

Uses

Different sources of media describe the Uses of 128-62-1 differently. You can refer to the following data:
1. Antitussive.
2. Antitussive

Definition

ChEBI: A benzylisoquinoline alkaloid that is 1,2,3,4-tetrahydroisoquinoline which is substituted by a 4,5-dimethoxy-3-oxo-1,3-dihydro-2-benzofuran-1-yl group at position 1, a methylenedioxy group at positions 6-7 and a methoxy group at position 8. Obtained from p ants of the Papaveraceae family, it lacks significant painkilling properties and is primarily used for its antitussive (cough-suppressing) effects.

Brand name

Tusscapine (Fisons);Bequitussin;Bisolvon compositum;Broncha-tulisan eucalyptol;Broncho-tulisan eucalyptol;Brosolin-rectocap;Codipect;Codyl cum expectoras;Coscotab;Degoran;Dettuso;Difimetus compositum;Finipect;Hederix;Lyabex retard;Nipaxan;Nitepax;Nosaclin;Noscalin;Noscapect;Noscarex;Noscatuss;Reatos;Rectolmin bronquial;Ribelfan;Stilco;Teletux;Tucotin;Tuscapin;Tussamine plus;Tussanil n;Tusscalman;Tussicure;Tussisedal;Tussoretard.

World Health Organization (WHO)

Noscapine, a centrally-acting cough suppressant and one of several alkaloids present in papaveretum (opium concentrate) was introduced into medicine many years ago. Subsequently, it was shown to increase the number of chromosomes in mammalian cell lines maintained in vitro. Although the clinical significance of this finding is uncertain, restrictive action was taken in a few countries since the possibility of a genotoxic effect cannot be excluded. On 4 December 1992 the European Committee on Proprietary Medicinal Products concluded that the available evidence does not indicate that use of noscapine holds any significant hazard. The Swedish Medical Products Agency also concluded that there is no justification to restrict the use of noscapine in women of childbearing age.

Biological Functions

Noscapine is a naturally occurring product of the opium poppy. It is a benzylisoquinoline with no analgesic or other CNS effects. Its antitussive effects are weak, but it is used in combination with other agents in mixtures for cough relief.

Hazard

Narcotic, use legally restricted.

Safety Profile

Moderately toxic by ingestion andsubcutaneous routes. Mutation data reported. Anantitussive. When heated to decomposition it emits toxicfumes of NOx.

References

Robiquet., Ann. Chim. Phys., 5,275 (1817)Matthiessen, Foster.,!. Chern. Soc., 16,342 (1863)Perkin, Robinson., ibid, 99,775 (1911)Polonovski, Polonovski., Bull. Soc. Chim. Fr., 47, 361 (1930)Lovell., Acta Cryst., 6, 869 (1953)Barnes., Can. f. Chern., 33,444 (1955)Safe, Moir., ibid, 160 (1964)Stereochemistry: Battersby, Spenser., Tetrahedron Lett., 11 (1964)

InChI:InChI=1/C22H23NO7.ClH/c1-23-8-7-11-9-14-20(29-10-28-14)21(27-4)15(11)17(23)18-12-5-6-13(25-2)19(26-3)16(12)22(24)30-18;/h5-6,9,17-18H,7-8,10H2,1-4H3;1H/t17-,18-;/m1./s1

Upstream product

• 30936-27-7 4-methoxy-6-methyl-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquinolin-6-ium iodide 
• 73563-23-2 3-bromo-6,7-dimethoxyphthalide 
• 5779-99-7 4-methoxybenzo[d][1,3]dioxole-5-carbaldehyde 
• 59259-90-4 5-(dimethoxymethyl)benzo[d][1,3]dioxole 
• 120-57-0 piperonal 
• 128580-99-4 4-Methoxy-5-(2',2'-dimethoxyethyl)carbimino-1,3-benzodioxolan 
• 569-31-3 meconin 
• 133932-07-7 6,7-dimethoxy-3-(trimethylsilyl)isobenzofuran-1(3H)-one 
• 550-10-7 hydrocotarnine 
• 108261-07-0 5,6,7,8-Tetrahydro-4-methoxy-6-methyl-1,3-dioxolo<4,5-g>isoquinolin-8-ol 
• 108261-02-5 -N-methylamino>acetaldehyde dimethyl acetal 
• 108460-85-1 amino>acetaldehyde dimethyl acetal 
• 1521-38-6 2,3-dimethoxybenzoic acid 
• 81474-46-6 4-bromo-7-methoxybenzo[1,3]dioxole-5-carboxylic acid methyl ester 

Downstream Products

• 550-10-7 hydrocotarnine 
• 20377-62-2 6-[(S)-hydroxy-((R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-methyl]-2,3-dimethoxy-benzophenone 
• 569-31-3 meconin 
• 75-50-3 trimethylamine 
• 92621-03-9 (3S)-6,7-dimethoxy-3-((R)-4-methoxy-5,6,7,8-tetrahydro-[1,3]dioxolo [4,5-g]isoquinolin-5-yl)isobenzofuran-1(3H)-one 
• 23942-99-6 (-)-α-narcotinediol 
• 483-89-6 2,3-dimethoxy-6-{[4-methoxy-6-(2-methylamino-ethyl)-benzo[1,3]dioxol-5-yl]-acetyl}-benzoic acid 
• 42011-37-0 (13aR)-9,10,14-trimethoxy-7ξ-methyl-13c-(toluene-4-sulfonyloxy)-(13ar)-5,8,13,13a-tetrahydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolinium; chloride 
• 41939-64-4 9,10,14-trimethoxy-7-methyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolinium; toluene-4-sulfonate 
• 82-54-2 4-methoxy-6-methyl-5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5-ol 
• 519-05-1 opianic acid 

Relevant articles and documents

New reactions of phthalidoisoquinoline alkaloids. Alkoxy exchange reactions and isomerisations of α- and β-narcotine

Substitution of the 7-methoxy group in α- and β-narcotine by other alkoxy groups occurs in an anhydrous ROH/RONa system. It is accompanied by isomerization in position 3 with preference for the α-configuration (5R, 3S). In an alkaline aqueous system (ROH/KOH or 1N KOH only isomerization in position 3 with preference for the β-configuration (5R, 3R) was observed. Some of the new 7-alkoxynarcotines were evaluated for their antitussive activity.

Synthesis and biological evaluation of novel biaryl type α-noscapine congeners

Natural α-noscapine, a known antitussive drug, is also now known to possess weak anticancer efficacy with relatively safe toxicity profile. In this study, we report synthesis and evaluation of novel biaryl type α-noscapine congeners designed by adding aryl unit to the tetrahydroisoquinoline part of natural α-noscapine core. Palladium catalyzed Suzuki cross coupling of 9-bromo α-noscapine with aryl boronic acids was employed using mild and inexpensive reagents to attain desired noscapinoids 5a-g in excellent yields. Screening anti-proliferative activity for new noscapinoids 5b-g, on human cancer cell lines resulted three compounds 5b, 5d and 5f as potent analogues, active against human breast epithelial (MCF-7), human cervix cancer (HeLa) and human lung adenocarcinoma epithelial (A549) cell lines.

Synthesis and click reaction of tubulin polymerization inhibitor 9-azido-α-noscapine

Abstract: An efficient protocol for the synthesis of tubulin polymerization inhibitor, 9-azido-α-noscapine 2h from 9-amino-α-noscapine 2g is developed using mild reaction conditions (t-butyl nitrite/trimethylsilyl azide in acetonitrile at room temperature). Operational simplicity, high product yield without formation of any side products are the advantages of this protocol. Further copper catalyzed click reactions of 9-azido-α-noscapine 2h with alkynes 6a–f resulted 9-triazolyl noscapinoids 7a–f resulted in excellent yields. Graphical Abstract: Developed an amicable protocol for the synthesis of 9-azido-α-noscapine from 9-amino-α-noscapineunder mild reaction conditions; was further derivatized to triazoles using click chemistry.[Figure not available: see fulltext.]

A new total synthesis of (±)-α-noscapine

A new, convergent total synthesis of (±)-α-noscapine was developed on a grams scale through the condensation of 3-trimethylsilyl-meconin derivative 9 and the iodized salt cotarnine derivative 20 as the key step. Staring from simple 2,3-dimethoxybenzoic acid, piperonal and 2,2-dimethoxyethanamine, through the traditional chemical processes to give the final product in 11.6% yield over 14 steps.