α-乙酰氧基-N-亚硝基吡咯烷的解离及其致癌代谢机理的理论研究  

Theoretical Study of Decomposition and Carcinogenic Metabolic Mechanism for α-Acetoxy-N-nitrosopyrrolidine

作　　者：李澜[1,2] 滕国凤[1] 孙淑娟[1] 李宗和[1] 

机构地区：[1]北京师范大学化学学院 [2]上海应用技术学院上海200235

出　　处：《化学学报》2007年第15期1459-1463,共5页Acta Chimica Sinica

摘　　要：用ab initio方法,在MP2/6-31G**水平下讨论了α-乙酰氧基-亚硝基吡咯烷(α-Acetoxy-NPYR)在各种条件下的解离反应机理,并对形成终致癌物B,C,D的代谢机理进行研究.发现在OH-和H2O作用下的解离都遵循羟基进攻羰基机理,OH-作用下是一个经四面体中间体阴离子的无位垒过程,H2O作用下有相对高的活化能(165.36kJ/mol).H3O+作用下是先形成阳离子产物的SN1过程,并没有发现遵循两种综合的解离情形.同时,羟基化产物异构化为终致癌物B,C,D是一个相对容易进行的过程.The decomposition mechanism of α-acetoxy-N-nitrosopyrrolidine has been theoretically investigated at the MP2/6-31G＊＊ level in various environments （OH^-, H2O, H3O^＋）. It was found that the decomposition mediated by OH^- and H2O was a ＂typical＂ carbonyl attack mechanism of ester hydrolysis. In the presence of H3O^＋, the decomposition is an SN1 process via an intermediate of N-nitrosiminium ion. A mixture of the carbonyl attack mechanism and SN1 process was found. The unstable decomposed product of α-hydroxy-nitrosopyrrolidine can be metabolized into active carcinogenic metabolites of B, C, and D, and the process involving isomerization and protonation is easy to occur.

关 键 词：α-乙酰氧基-N-亚硝基吡咯烷 解离 致癌 

分 类 号：R730.2[医药卫生—肿瘤]