4192-31-8Relevant articles and documents
Method for preparing bioactive (S)-(-)-nicotine
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Paragraph 0065-0067; 0072-0074; 0079-0081; 0086-0089; ..., (2021/07/17)
The invention relates to the field of organic synthesis, and discloses a method for preparing bioactive (S)-(-)-nicotine. The method comprises the steps of carrying out first reaction on methyl nicotinate and tert-butyl succinic acid diester, and then carrying out second reaction; and carrying out contact reaction on the system after the second reaction and an acidic material to obtain 4-oxo-4-(3-pyridyl) butyric acid; carrying out asymmetric reduction reaction on 4-oxo-4-(3-pyridyl) butyric acid and (R)-(+)-2-methyl-CBS-oxazoborane to obtain 5-(3-pyridyl) dihydrofuran-2 (3H)-ketone; carrying out third reaction on the 5-(3-pyridyl) dihydrofuran-2 (3H)-ketone and methylamine hydrobromide to obtain 1-methyl-5-(3-pyridyl)-2-pyrrolidone; and carrying out fourth reaction on the 1-methyl-5-(3-pyridyl)-2-pyrrolidone and a reducing agent to obtain the bioactive (S)-(-)-nicotine. According to the method, the bioactive body (S)-(-)-nicotine can be obtained with high yield and high purity.
Preparation method of artificially synthesized nicotine
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Paragraph 0025-0029; 0034, (2019/10/04)
The invention discloses a preparation method of artificially synthesized nicotine, and belongs to the technical field of chemical synthesis. According to the synthesis method of a racemate (+/-)-(R,S)-nicotine and a natural optical active enantiomer (-)-(S)-nicotine, nicotinate and diester of succinic acid (or N-alkyl succinimide) are taken as the primary raw materials; and defects of a conventional nicotine synthesis technology such as difficulty for massive production, high cost, and the like, are overcome. Specifically, the provided synthesis method has the advantages that the primary raw materials are easily available, the preparation technology is simple, the cost is low, the prepared nicotine does not contain any other harmful tobacco compound, and the preparation method is suitable for industrial large-scale production.
Evaluation of Nitrosamide Formation in the Cytochrome P450-Mediated Metabolism of Tobacco-Specific Nitrosamines
Carlson, Erik S.,Upadhyaya, Pramod,Hecht, Stephen S.
, p. 2194 - 2205 (2016/12/26)
N′-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are carcinogenic tobacco-specific nitrosamines believed to play a vital role in the initiation of tobacco-related cancers. For their carcinogenicities to be exhibited, both NNN and NNK must be metabolically activated by cytochrome P450s, specifically P450 2A6 and P450 2A13, respectively. Prior research has focused on α-hydroxylation, which leads to the formation of several DNA adducts that have been identified and quantified in vivo. However, some studies indicate that P450s can retain substrates within their active sites and perform processive oxidation. For nitrosamines, this would oxidize the highly unstable α-hydroxynitrosamines to potentially more stable nitrosamides, which could also alkylate DNA. Thus, we hypothesized that both NNN and NNK are processively oxidized in vitro to nitrosamides by P450 2A6 and P450 2A13, respectively. To test this hypothesis, we synthesized the NNN- and NNK-derived nitrosamides, determined their half-lives at pH 7.4 and 37 °C, and monitored for nitrosamide formation in an in vitro P450 system with product analysis by LC/NSI+-HRMS/MS. Half-lives of the nitrosamides were determined by HPLC-UV and ranged from 7-35 min, which is more than 40 times longer than the corresponding α-hydroxynitrosamines. Incubation of NNN in the P450 2A6 system resulted in the formation of the nitrosamide N′-nitrosonorcotinine (NNC) at low levels. Similarly, the nitrosamide 4-(methylnitrosamino)-1-(3-pyridyl)-1,4-butanedione (CH2-oxo-NNK) was detected in low amounts in the incubation of NNK with the P450 2A13 system. The other possible NNK-derived nitrosamide, 4-(nitrosoformamido)-1-(3-pyridyl)-1-butanone (CH3-oxo-NNK), was not observed in the P450 2A13 reactions. CH2-oxo-NNK readily formed O6meGua in reactions with dGuo and calf thymus DNA. These results demonstrate that NNC and CH2-oxo-NNK are novel metabolites of NNN and NNK, respectively. Though low-forming, their increased stability may allow for mutagenic DNA damage in vivo. More broadly, this study provides the first account of a cytochrome P450-mediated conversion of nitrosamines to nitrosamides, which warrants further studies to determine how general this phenomenon is in nitrosamine metabolism.
Chemoenzymatic and yeast-catalysed synthesis of diastereomeric ethyl γ-phenyl and γ-(n-pyridyl)paraconates
Forzato, Cristina,Furlan, Giada,Nitti, Patrizia,Pitacco, Giuliana,Valentin, Ennio,Zangrando, Ennio,Buzzini, Pietro,Goretti, Marta,Turchetti, Benedetta
, p. 2026 - 2036 (2008/12/23)
The synthesis of γ-phenyl and γ-(n-pyridyl)paraconates was accomplished by chemical reduction of their respective ketodiester precursors followed by cyclisation of the resulting hydroxy diester intermediates. The cis- and trans-lactones thus obtained were separated and separately subjected to enzymatic hydrolysis with HLAP. The cis-lactonic esters had enantiomeric excesses ranging from 94% to 99%, while for the trans-isomers the ee's ranged from 80% to 93%. The same ketodiester precursors were subjected to reduction with a series of yeasts. The absolute configuration of trans-(-)-2-pyridyl paraconic acid was assigned by means of X-ray analysis of its hydrobromide salt, while the absolute configurations of the other lactones were determined via analysis of their respective CD curves.
Derivatives of 4-hydroxybutanoic acid and of its higher homologue as ligands of γ(g)-hydroxybutyrate (ghb) receptors, pharmaceutical compositions containing same and pharmaceutical uses
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Page/Page column 8, (2010/02/11)
The invention concerns the field of synthesis organic chemistry applied to the pharmaceutical field and concerns novel derivatives of 4-hydroxybutanoic acid and its higher homologue, 5-hydroxypentanoic acid, their crotonic homologues, pharmaceutical compo
Compound having effect of promoting neuron differentiation
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, (2008/06/13)
A novel cystacycline derivative which has an excellent effect of promoting the differentiation of neurons and is useful as a remedy for central nervous system disorders, a remedy for peripheral nerve disorders, etc.