高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

N,N-二(对氟苄基)-N'-(2',3'-二脱氧-3'-硫代胞苷)甲脒水解反应的理论研究

张成华1, 薛英1,2, 郭勇1, 鄢国森1   

    1. 四川大学化学学院, 成都 610064;
    2. 四川大学生物治疗国家重点实验室, 成都 610041
  • 收稿日期:2008-09-28 修回日期:1900-01-01 出版日期:2008-12-10 发布日期:2008-12-10
  • 通讯作者: 薛英

Theoretical Study on the Hydrolysis of N,N-Bis(p-fluorobenzyl)-N′-(2′,3′-dideoxy-3′-thiacytidinyl) Formamidine

ZHANG Cheng-Hua1, XUE Ying1,2*, GUO Yong1, YAN Guo-Sen1   

    1. College of Chemistry, Sichuan University, Chengdu 610064, China;
    2. State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
  • Received:2008-09-28 Revised:1900-01-01 Online:2008-12-10 Published:2008-12-10
  • Contact: XUE Ying

PDF (PC)

摘要： 采用密度泛函理论方法B3LYP/6-31++G(d,p)//B3LYP/6-31G(d,p)和导体极化连续模型B3LYP/CPCM/6-31++G(d,p)方法对苯环对位上有F取代的N,N-二(对氟苄基)-N′-(2′,3′-二脱氧-3′-硫代胞苷)甲脒(FBFA-3TC)水解反应机理和溶剂效应进行了研究. 考虑两条可能反应途径: 水分子首先进攻C=N双键的途径(Path A)和先进攻C-N单键的途径(Path B). 计算结果表明, 气相和水中两条途径的第一步都是速率控制步骤, Path A 比Path B 更有利. 对优势途径Path A的第二步反应的进一步研究发现, 中间体的羟基H原子转移到双键N比单键N更容易, 从而形成2′,3′-二脱氧-3′-硫代胞苷(3TC)的最终水解产物.

关键词: N,N-二(对氟苄基)-N′-(2′,3′-二脱氧-3′-硫代胞苷)甲脒, 水解, 密度泛函理论, 导体极化连续模型

Abstract: Theoretical study on the hydrolysis mechanism of N,N-bis(p-fluorobenzyl)-N′-(2′,3′- dideoxy-3′-thiacytidinyl)formamidine(FBFA-3TC) was carried out at the B3LYP/6-31G(d,p) level. The solvent effect was evaluated using the conductor polarizable continuum model(CPCM) through the single point energy calculations at the B3LYP/6-31++G(d,p) level. Two reaction pathways are considered. Path A is the addition of water molecule to the C=N double bond in the amidine group in its first step and Path B is the attack of water molecule to the C-N single bond in its first step. The calculated results indicate that the first step in both pathways is the rate-limiting process and Path A is more favorable than Path B in the gas phase and in water. The solvent effects are not distinct. It is also found that the second step in Path A proceeds preferably according to Channel a, in which the second H atom of water transfers to the N atom in double bond of the amidine group, leading to products the modified cytidine and N,N-dibenzyl formamide.

Key words: N,N-Bis(p-fluorobenzyl)-N′-(2′,3′-dideoxy-3′-thiacytidinyl)formamidine, Hydrolysis, Density functional theory, Conductor polarizable continuum model(CPCM)

中图分类号: 

TrendMD: