13078-04-1Relevant articles and documents
SYNTHESIS OF TOBACCO ALKALOIDS VIA TERTIARY AZIDES
Alberici, Gilles F.,Andrieux, Jean,Adam, Gerard,Plat, Michel M.
, p. 1937 - 1940 (1983)
A convenient new synthesis of different tobacco alkaloids, such as nicotine and anabasine is described, using as key step the SCHMIDT reaction applied to tertiary alcohols.
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
Yang, Chi-Ming,Tanner, Dennis D.
, p. 616 - 620 (1997)
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.
From building block to natural products: A short synthesis and complete NMR spectroscopic characterization of (±)-anatabine and (±)-anabasine
Saloranta, Tiina,Leino, Reko
, p. 4619 - 4621 (2011)
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.
Direct α-C-H bond functionalization of unprotected cyclic amines
Chen, Weijie,Ma, Longle,Paul, Anirudra,Seidel, Daniel
, p. 165 - 169 (2018/02/06)
Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the α-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.
Toward Pyridine-Heterocycle Patterns through Prins and Aza-Prins Cyclisations: Application to a Short Synthesis of (±)-Anabasine
Colin, Olivier,Greck, Christine,Prim, Damien,Thomassigny, Christine
, p. 7000 - 7005 (2016/02/19)
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.
Hydroformylation of alkenylamines. Concise approaches toward piperidines, quinolizidines, and related alkaloids
Airiau, Etienne,Girard, Nicolas,Pizzeti, Marianna,Salvadori, Jessica,Taddei, Maurizio,Mann, Andre
supporting information; experimental part, p. 8670 - 8673 (2011/02/28)
Linear hydroformylation of N-protected allyl- or homoallylamines (cyclohydrocarbonylation: CHC), followed by a reductive amination constitute the two key steps toward convenient routes to aza-heterocycles.
One-pot formation of piperidine- and pyrrolidine-substituted pyridinium salts via addition of 5-alkylaminopenta-2,4-dienals to N-acyliminium ions: Application to the synthesis of (±)-nicotine and analogs
Peixoto, Sabrina,Nguyen, Tuan Minh,Crich, David,Delpech, Bernard,Marazano, Christian
supporting information; body text, p. 4760 - 4763 (2010/12/25)
Addition of 5-alkylaminopenta-2,4-dienals onto N-acyliminium ions, generated in situ from α-hydroxycarbamates derived from pyrrolidine or piperidine, in the presence of zinc triflate, followed by dehydrative cyclization, allowed the formation of pyridinium salts substituted at their 3-position by a five- or six-membered nitrogen heterocycle. Subsequent N-dealkylation of the pyridinium moiety and deprotection of the secondary amine or reduction of the carbamate function led to (±)-nicotine and analogs.
Synthesis of 2-arylpiperidines by palladium couplings of aryl bromides with organozinc species derived from deprotonation of N-Boc-piperidine
Coldham, Iain,Leonori, Daniele
supporting information; experimental part, p. 3923 - 3925 (2009/05/31)
(Figure Presented) The organolithium species derived from proton abstraction of N-Boc-piperidine with s-BuLi and TMEDA can be transmetalated to the organozinc reagent, and this organometallic species can be coupled directly with aryl bromides in a Negishi-type reaction using palladium catalysis with the ligand tri-tert-butylphosphine (t-Bu3P-HBF4). The chemistry was applied to a very short synthesis of the alkaloid anabasine.
Palladium-catalyzed direct C-H arylation of N-iminopyridinium ylides: Application to the synthesis of (±)-anabasine
Larivee, Alexandre,Mousseau, James J.,Charette, Andre B.
, p. 52 - 54 (2008/09/20)
Palladium-catalyzed direct C-H arylation of N-iminopyridinium ylides provides a powerful and versatile method for the synthesis of functionalized piperidines in good yields. Chemoselective functionalization of the pyridinium ring in the presence of a pyridine substituent is possible as exemplified by the expedient synthesis of anabasine in 61% overall yield over three steps. Copyright
Antibody-catalyzed oxidative degradation of nicotine using riboflavin
Dickerson, Tobin J.,Yamamoto, Noboru,Janda, Kim D.
, p. 4981 - 4987 (2007/10/03)
Tobacco abuse remains a major cause of death worldwide despite ample evidence linking nicotine to various disease states. Consequently, immunopharmacotherapeutic approaches for the treatment of nicotine abuse have received increasing attention. Although a number of nicotine-binding antibodies have been disclosed, no antibody catalysts exist which efficiently degrade nicotine into pharmacologically inactive substances. Herein, we report the first catalytic antibodies which can oxidatively degrade nicotine. These biocatalysts use the micronutrient riboflavin and visible light as a source of singlet oxygen for the production of reactive oxygen species. Along with various known nicotine metabolites, antibody-catalyzed nicotine oxidations produce two novel nicotine oxidation products that were also detected in control ozonation reactions of nicotine. The reaction is efficient, with multiple turnovers of catalyst observed and total consumption of nicotine attained. These results demonstrate the potential of harnessing riboflavin as an endogenous sensitizer for antibody-catalyzed oxidations and demonstrate a new approach for the development of an active vaccine for the treatment of nicotine addiction using in vivo catalytically active antibodies.
