Studies on the in vivo biotransformation of the tobacco alkaloid beta-nicotyrine.
Studies on the in vivo biotransformation of the tobacco alkaloid beta-nicotyrine.
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DOI：
10.1021/tx990124t
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发表时间：
2000-04
影响因子：
4.1
通讯作者：
Xin Liu;K. Castagnoli;C. J. Van der Schyf;N. Castagnoli
中科院分区：
文献类型：
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作者：
Xin Liu;K. Castagnoli;C. J. Van der Schyf;N. Castagnoli
本文报道了烟草生物碱1-甲基-2-（3-吡啶基）吡咯（β-二烯烟碱）在新西兰白色家兔体内代谢转归的研究结果。两种先前表征的代谢物5-羟基-1-甲基-5-（3-吡啶基）-2-吡咯烷酮（5-羟基可替宁）和2-羟基-1-甲基-5-（3-吡啶基）-3-吡咯啉-2-酮在给药动物的尿液中以低浓度存在。β-二烯烟碱的主要尿液代谢产物鉴别为顺式-3 '-羟基-1-甲基-5-（3-吡啶基）-2-吡咯烷酮（顺式-3'-羟基可替宁），（S）-尼古丁主要尿液代谢产物的非对映异构体。产生顺式-3 '-羟基可替宁的途径拟定通过2-羟基-1-甲基-5-（3-吡啶基）吡咯（一种假定的细胞色素P450生成的β-二烯烟碱代谢物）的自氧化，然后还原所得3-羟基-3-吡咯啉-2-酮物质中存在的碳-碳双键进行。该建议得到了2-乙酰氧基-1-甲基-5-（3-吡啶基）吡咯（假定羟基吡咯中间体的潜在形式）向顺式-3 '-羟基可替宁的体内生物转化的支持。提供了5-羟基-1-甲基-5-（3-吡啶基）-3-吡咯啉-2-酮向5-羟基可替宁的体内转化作为支持拟定还原步骤的证据。
This paper reports the results of studies on the in vivo metabolic fate of the tobacco alkaloid 1-methyl-2-(3-pyridinyl)pyrrole (beta-nicotyrine) in New Zealand white rabbits. Two previously characterized metabolites, 5-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (5-hydroxycotinine) and 2-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one, were present in low concentrations in the urine of the treated animals. The major urinary metabolite of beta-nicotyrine was identified as cis-3'-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (cis-3'-hydroxycotinine), the diastereoisomer of the major urinary metabolite of (S)-nicotine. The pathway leading to cis-3'-hydroxycotinine is proposed to proceed via autoxidation of 2-hydroxy-1-methyl-5-(3-pyridinyl)pyrrole, a postulated cytochrome P450-generated metabolite of beta-nicotyrine, followed by reduction of the carbon-carbon double bond present in the resulting 3-hydroxy-3-pyrrolin-2-one species. This proposal is supported by the in vivo biotransformation of 2-acetoxy-1-methyl-5-(3-pyridinyl)pyrrole, a latent form of the putative hydroxypyrrole intermediate, to cis-3'-hydroxycotinine. The in vivo conversion of 5-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one to 5-hydroxycotinine is offered as evidence that supports the proposed reduction step.