51095-86-4Relevant academic research and scientific papers
Racemic synthesis of 2′-substituted nicotine analogs
Rouchaud, Anne,Kem, William R.
experimental part, p. 161 - 166 (2012/05/05)
The chemical and pharmacological properties of 2′-substituted nicotines are poorly understood relative to other substituted nicotines. We developed a practical synthesis of the key intermediate (6)-2′- cyanonicotine using the Polonovski reaction. Alkylation of (6)-2′- cyanonicotine with Grignard reagents led to several 2′-alkylnicotines; (6)-2′-aminomethylnicotine, (6)-2′-hydroxymethylnicotine, and (6)-2′- carbamoylnicotine were also synthesized..
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.
First asymmetric oxidation of tertiary amines by cyclohexanone monooxygenase
Ottolina, Gianluca,Bianchi, Silvia,Belloni, Barbara,Carrea, Giacoma,Danieli, Bruno
, p. 8483 - 8486 (2007/10/03)
Cyclohexanone monooxygenase catalyzes the asymmetric oxidation of some tertiary amines to amine N-oxides. The structure of the amine markedly influences the enantiomeric excess of products.
The biosynthesis of [5'-14C]cotinine and other radiolabeled nicotine metabolites
Tsai, Mui-Chiung,Sai, Yang,Li, Yan,Aislaitner, George,Gorrod, John W.
, p. 387 - 407 (2007/10/03)
The present study describes the biosynthesis and isolation of the major radiolabeled nicotine metabolites formed using phenobarbitone (PB)-induced rabbit hepatic homogenates (10,000 g fraction). The optimal incubation and extraction methods for cotinine formation from non-labeled nicotine were established. The biosynthesis and isolation of [5'-14C]cotinine and other radiolabeled metabolites such as [2'-14C]nornicotine and [4-14C]-(3-pyridyl)-4-oxobutyric acid, from commercially available [2'-14C]nicotine, were carried out using the developed methods. Cotinine was isolated using preparative silica gel TLC, whereas the other metabolites were obtained using a cation-exchange HPLC method. This study showed that in addition to the two major metabolites (i.e. cotinine and nornicotine), 4-(3-pyridyl)-4-oxo-butyric acid, 3-hydroxycotinine, norcotinine, nicotine-1'-N-oxide and cotinine-1-N-oxide were also formed when PB-induced rabbit hepatic homogenates were used. Two further metabolites of unknown structure were detected. However, the isolation and further purification were only carried out on cotinine, nornicotine and 4-(3-pyridyl)-4-oxo-butyric acid.
Diastereospecific kinetics of nicotine N'-oxidation in rat liver microsomes
Nakajima,Iwata,Yoshida,Yamamoto,Kuroiwa
, p. 127 - 135 (2007/10/03)
1. In kinetic studies, both Eadie-Hofstee plots for cis- and trans-nicotine-1'-N-oxide formation from nicotine in rat liver microsomes were linear. For the formation of cis- and trans-nicotine-1'-N-oxide, the apparent k(m) were 0.240 ± 0.069 and 1.524 ± 0.951 mM respectively. Corresponding V(max) were 1.52 ± 0.48 and 1.19 ± 0.74 nmol/mg/min respectively. 2. The formation of cis-nicotine-1'-N-oxide was greater than the formation of trans-nicotine-1'-N-oxide in rat liver microsomes and the intrinsic clearance of cis-nicotine-1'-N-oxide formation was 8.1-fold greater than that of trans-nicotine-1'-N-oxide formation. 3. The formation of both cis- and trans-nicotine-1'-N-oxide in rat liver microsomes was inhibited by the addition of 1-(1-naphthyl)-2-thiourea or by heat-treatment of microsomes. 2-Diethylaminoethyl-2, 2-diphenylvalerate (SKF525A) and carbon monoxide did not affect these activities even at high concentrations. 4. Formations of cis- and trans-nicotine-1'-N-oxide correlated significantly with each other (r = 0.862, p 0.01). These results suggested that the same flavin-containing monooxygenase (FMO) isoform is responsible for the formation of cis- and trans-nicotine-1'-N-oxide in rat liver.
Biomimetic oxidation of nicotine with hydrogen peroxide and 5-ethylflavin mononucleotide perchlorate
Chaudhary, Shveta,Awasthi, Abha,Chauhan, S. M. S.
, p. 294 - 297 (2007/10/03)
The biomimetic oxidation of nicotine 4 with hydrogen peroxide in the presence of 5-ethylflavin mononucleotide perchlorate gives the nicotine-N'-oxide 5 in higher yield in AOT reverse micelles than in homogeneous medium.
