2743-90-0

Basic information

• Product Name: (R,S)-ANATABINE
• Synonyms: D,L-ANATABINE;1,2,3,6-TETRAHYDRO-2,3'-BIPYRIDINE;(R,S)-ANATABINE;ANATABINE, (+/-)-(RG);(+/-)-Anatabine, 3-(1,2,3,6-Tetrahydropyridin-2-yl)pyridine, 2-(Pyridin-3-yl)-1,2,3,6-tetrahydropyridine;Anatabine, froM Nicotiana tabacuM L.;Anatabine, 97%, from Nicotiana tabacum L.
• CAS NO: 2743-90-0
• Molecular Formula: C₁₀H₁₂N₂
• Molecular Weight: 160.22
• Product Categories: Metabolites;Nicotine Derivatives;Aromatics;Heterocycles;Metabolites & Impurities
• Mol File: 2743-90-0.mol

Chemical Properties

• Boiling Point: 136
• Flash Point: 116.5 °C
• Appearance: Light Yellow Oil
• Density: 1.045 g/cm³
• Storage Temp.: Amber Vial, Refrigerator, Under Inert Atmosphere
• Solubility: ≤15mg/ml in DMSO;15mg/ml in dimethyl formamide
• PKA: 8.84±0.40(Predicted)
• Stability: Hygroscopic, Light Sensitive
• CAS DataBase Reference: (R,S)-ANATABINE(CAS DataBase Reference)
• NIST Chemistry Reference: (R,S)-ANATABINE(2743-90-0)
• EPA Substance Registry System: (R,S)-ANATABINE(2743-90-0)

Safety Data

• Statements: 25-36
• Safety Statements: 24/25
• RIDADR: 2810
• HazardClass: IRRITANT
• Hazardous Substances Data: 2743-90-0(Hazardous Substances Data)

Usage

Uses

Used in Tobacco Use Detection:
(R,S)-Anatabine is used as a biomarker for tobacco use, particularly when individuals are using nicotine-containing products such as gum, patches, inhalers, and medications. The detection of (R,S)-anatabine in urine helps confirm tobacco consumption.
Used in Neurodegenerative Disease Research:
(R,S)-Anatabine is used as a research compound for studying its potential effects on neurodegenerative diseases. It has been shown to diminish amyloid-β production in vitro and in vivo, suggesting a possible role in the treatment or prevention of conditions like Alzheimer's disease.
Used in Pharmaceutical Research:
(R,S)-Anatabine is used as a compound in the development of new pharmaceuticals, particularly those targeting neurodegenerative diseases and tobacco addiction. Its ability to increase nicotine self-administration and inhibit NF-κB activation makes it a promising candidate for further research and development in these areas.

in vitro

anatabine dose-dependently lowered aβ1-40 and aβ1-42 levels and reduced sappβ production without any effects on sappα levels. anatabine lowered aβ production by mainly impacting the β-cleavage of app. anatabine lowered nfκb activation. anatabine inhibited bace-1 transcription and reduced bace-1 protein levels in human neuronal like shsy-5y cells. (r,s)-anatabine also dose dependently inhibits nf-κb activation [1].

in vivo

in a transgenic mouse model of alzheimer's disease, acute treatment with anatabine for 4 days significantly lowered brain soluble aβ1-40 and aβ1-42 levels [1].

references

[1] paris d, beaulieu-abdelahad d, bachmeier c, et al. anatabine lowers alzheimer's aβ production in vitro and in vivo[j]. european journal of pharmacology, 2011, 670(2): 384-391.

Upstream product

• 1027559-83-6 Benzhydrylidene-((Z)-5-chloro-1-pyridin-3-yl-pent-3-enyl)-amine 
• 133692-30-5 N-allyl-1-(pyridin-3-yl)methanimine 
• 1476-11-5 Z-1,4-dichlorobutene 
• 175441-83-5 N-(diphenylmethylene)-1-(pyridin-3-yl)methanamine 
• 1159977-12-4 tert-butyl 3,6-dihydro-[2,3'-bipyridine]-1(2H)-carboxylate 
• 500-22-1 3-pyridinecarboxaldehyde 
• 2524-49-4 3-butene-1-amine 
• 1332337-79-7 N-(prop-2-en-1-yl)-1-(pyridin-3-yl)but-3-en-1-amine 
• 1332337-78-6 N'-(1-(pyridin-3-yl)-but-3-enyl)-N,N-dimethylsulfonamide 
• 1332337-77-5 N,N-(dimethylsulfamoyl)-3-pyridinylaldimine 
• 1236361-13-9 (+/-)-N-methylanatabine-N-oxide 
• 3731-52-0 3-Aminomethylpyridine 

Downstream Products

• 581-50-0 2,3'-bipyridine 
• 13078-04-1 anabasine 
• 1159977-12-4 tert-butyl 3,6-dihydro-[2,3'-bipyridine]-1(2H)-carboxylate 

Relevant articles and documents

A Practical and Efficient Synthesis of (±)-Anatabine

A new efficient synthesis of racemic anatabine is reported. The title target was obtained in an excellent overall yield of 70%, by a five-step synthesis, using cheap reagents and mild reaction conditions.

Preparation method for anatabine

The invention discloses a preparation method for anatabine. The method comprises the steps of (1) enabling 3-amino methyl pyridine to react with benzophenone to obtain an intermediate 1; (2) synthesizing an intermediate 2 by the intermediate 1 and cis-1,4-dichloro-2-butene; (3) enabling the intermediate 2 to react with Boc anhydride to obtain an intermediate 3; and (4) removing a Boc group from the intermediate 3 to obtain an intermediate 4 to obtain an anatabine product. The anatabine prepared by adopting the method is high in yield, high in purity and good in quality.

Toward Pyridine-Heterocycle Patterns through Prins and Aza-Prins Cyclisations: Application to a Short Synthesis of (±)-Anabasine

The formation of pyridine-containing bisheterocycles through a Prins-type cyclisation is described. Pyridine-tetrahydropyran and pyridine-piperidine conjugates could be efficiently obtained using various carbaldehydes including dicarbaldehydes, and either homoallylic alcohols or a homoallylic amine. Selective partial or complete hydrogenation led to new bisheterocycle combinations. A two-step sequence involving an aza-Prins cylisation allowed us to prepare the alkaloid anabasine.

METHODS OF SYNTHESIZING ANATABINE

Anatabine is obtained by reacting benzophenoneimine with 3-aminomethyl pyridine to form benzylhydrylidene-pyridin-3-yl-methyl-amine. The benzylhydrylidene-pyridin-3-yl-methyl-amine is treated with a non-nucleophilic base and a dielectrophile, such as cis-1,4-dichloro-2-butene, followed by acidification, then basification, to provide anatabine. The resulting anatabine is substantially free from contaminants and displays good stability. In an alternative embodiment, the benzylhydrylidene-pyridin-3-yl-methyl-amine may be used in the synthesis of other alkaloids such as anabasine, nornicotine, N-methylanabasine, and anabaseine.

From building block to natural products: A short synthesis and complete NMR spectroscopic characterization of (±)-anatabine and (±)-anabasine

A short and straightforward synthesis of the racemic tobacco alkaloids anatabine and anabasine in five and six steps, respectively, from 3-pyridinecarboxaldehyde utilizing Barbier-type Zn-mediated allylation and ring-closing olefin metathesis, as the key steps, is reported. Additionally, a complete NMR spectroscopic analysis of the final products is carried out and full assignment of the NMR spectra of anatabine and anabasine with accurate coupling constants is accomplished and reported here for the first time.

A convenient racemic synthesis of two isomeric tetrahydropyridyl alkaloids: Isoanatabine and anatabine

(Chemical Equation Presented) Anatabine is a major alkaloid in Nicotiana tabacum and its isomer, isoanatabine, was recently found in a marine worm. Reduction of 1-methylpyridinium iodide with sodium borohydride gave 1-methyl-3-piperideine, which was transformed with hydrogen peroxide into the N-oxide. Reaction of the N-oxide successively with trifluoroacetic anhydride and potassium cyanide gave 2-cyano-1-methyl-3-piperideine. Its reaction with 3-pyridylmagnesium chloride gave (±)-N-methyl-isoanatabine. This was transformed with m-chloroperbenzoic acid into the N-oxide which was N-demethylated with iron(II) sulfate, giving (±)-isoanatabine. The successive applications of literature procedures for the N-demethylation by decomposition of N-oxide contributed to the knowledge of the mechanism of this oxidative rearrangement. On the other hand, the reduction of 1-methylpyridinium iodide with sodium borohydride and with potassium cyanide present since the start of the reaction in a two layer ether-water system, gave 2-cyano-1-methyl-4-piperideine. This was transformed into (±)-anatabine by the same sequence of reactions used for the synthesis of (±)- isoanatabine.

A simple synthesis of (±)-1,2,3,6-tetrahydro-2,3′-bipyridine (anatabine) and (±)-3-(2-piperidinyl)pyridine (anabasine) from lithium aluminum hydride and pyridine

The hydrolysis of a pyridine solution of lithium tetrakis(N-dihydropyridyl)aluminate (LDPA), which was prepared at 0°C, yields a mixture of 1,4-, 1,2-, and 2,5-dihydropyridines (DHPs) in a ratio of 26:37:38. The subsequent reversible base-catalyzed condensation of a 1:1 mixture of 1,2- and 2,5-DHPs carried out in the presence of oxygen affords an 89% yield of (±)-anatabine. When the reaction mixture is allowed to stand in the presence of oxygen, anabasine is slowly formed from anatabine by the reaction of the residual DHPs. Anatabine can also be converted into (±)-anabasine by catalytic hydrogenation.

Regioselective alkylation of N-(diphenylmethylidine)-3-(aminomethyl)pyridine: A simple route to minor tobacco alkaloids and related compounds

A simple synthetic route to minor tobacco alkaloids and related compounds is described involving regioselective alkylation of N-(diphenylmethylidine)-3-(aminomethyl)pyridme with a suitable dielectrophile.