[3'-O-甲基硫代甲基胸苷和3'-O-甲基亚磺酰基甲基胸苷的X射线结构研究——潜在的HIV抑制剂]

[X-ray structural study of 3'-O-methylthiomethylthymidine and 3'-O-methylsulfinylmethylthymidine--potential inhibitors of HIV].

作者信息

Bochkarev A V, Zavgorodniĭ S G, Zhdanov A S, Gurskaia G V

出版信息

Bioorg Khim. 1995 Mar;21(3):206-11.

Abstract

The molecular and crystalline structures of deoxiribonucleoside analogs: 3'-O-methylthiomethylthymidine monohydrate dT(CH2SMe).H2O and 3'-O-methylsulphinylmethylthymidine dT(CH2SOMe) were determined. The space group of dT(CH2SMe).H2O crystals is P2(1), the parameters of the elementary cell are a = 10.417(1), b = 4.912(2), c = 15.969(2) A, beta = 107.23(1) degrees, V = 780.5 A3, Z = 2, R = 3.8%. The crystals of dT(CH2SOMe have a space group P2(1)2(1)2(1), the elementary cell parameters are a = 8.858(2), b = 9.303(1), c = 17.698(2) A, V = 1458.3 A3, Z = 4, R = 2.8%. The dT(CH2SMe) and dT(CH2SOMe) molecules are characterized by an anti-conformation relative to the glycoside bond (angles chi (O4'-C1'-N1-C2) are equal to -116.2 degrees and -148.8 degrees), a gauche(+)-conformation relative to the exocyclic bond C4'-C5' (angles phi CO (C3'-C4'-C5'-O5') are equal to 52.1 degrees and 41.1 degrees). The conformation of the furanose cycle in the dT(CH2SMe) molecule is described by C2'-endo-C3'-exo (P = 167.8 degrees, psi m = 34.8 degrees) and in the dT(CH2SOMe) molecule by C2'-endo-C1'-exo (P = 148.4 degrees, psi m = 35.4 degrees). The structures studied were compared with 3'-azido-3'-deoxythymidine (AZT) and thymidine.

摘要

测定了脱氧核糖核苷类似物

3'-O-甲基硫代甲基胸苷一水合物dT(CH2SMe).H2O和3'-O-亚磺酰基甲基胸苷dT(CH2SOMe)的分子结构和晶体结构。dT(CH2SMe).H2O晶体的空间群为P2(1)，晶胞参数为a = 10.417(1)，b = 4.912(2)，c = 15.969(2) Å，β = 107.23(1)°，V = 780.5 Å3，Z = 2，R = 3.8%。dT(CH2SOMe)晶体的空间群为P2(1)2(1)2(1)，晶胞参数为a = 8.858(2)，b = 9.303(1)，c = 17.698(2) Å，V = 1458.3 Å3，Z = 4，R = 2.8%。dT(CH2SMe)和dT(CH2SOMe)分子相对于糖苷键呈反式构象（χ(O4'-C1'-N1-C2)角分别为-116.2°和-148.8°），相对于环外键C4'-C5'呈gauche(+)构象（φCO(C3'-C4'-C5'-O5')角分别为52.1°和41.1°）。dT(CH2SMe)分子中呋喃糖环的构象由C2'-endo-C3'-exo描述（P = 167.8°，ψm = 34.8°），dT(CH2SOMe)分子中由C2'-endo-C1'-exo描述（P = 148.4°，ψm = 35.4°）。将所研究的结构与3'-叠氮-3'-脱氧胸苷（AZT）和胸苷进行了比较。