trimethylsilylated 2-thiopyrimidine | 52523-23-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: trimethylsilylated 2-thiopyrimidine
• 英文别名: 2-trimethylsilylmercaptopyrimidine；(S-2-N2C4H3)Si(CH3)3；Trimethyl(pyrimidin-2-ylsulfanyl)silane
• CAS: 52523-23-6
• 化学式: C₇H₁₂N₂SSi
• 分子量: 184.337
• InChiKey: ZOUYJJQVKYUPKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  trimethylsilylated 2-thiopyrimidine 、 cadmium(II) chloride 以 N,N-二甲基甲酰胺 为溶剂， 以73%的产率得到[Cd(pyrimidine thiolate)2]
  参考文献：
  名称：

  Synthesis and Structure of the Group 12 Pyrimidinethiolate Complexes _∞ ³ [Zn(S‐2‐N ₂ C ₄ H ₃ ) ₂ ], _∞ ² [Cd(S‐2‐N ₂ C ₄ H ₃ ) ₂ ], [Hg(S‐2‐N ₂ C ₄ H ₃ ) ₂ ] and[Cd(S‐2‐N ₂ C ₄ H ₃ ) ₂ (tmeda)]

  摘要：

  AbstractThe pyrimidinethiolate complexes ∞3[Zn(S‐2‐N2C4H3)2],∞2[Cd(S‐2‐N2C4H3)2] and [Hg(S‐2‐N2C4H3)2] have been prepared by reaction of MCl2 (M = Zn, Cd, Hg) with 2 equiv. of Me3SiS‐2‐N2C4H3 in organic solvents, whilst [Cd(S‐2‐N2C4H3)2(tmeda)] was obtained by recrystallisation of∞2[Cd(S‐2‐N2C4H3)2] in TMEDA at 40 °C. The structures of the complexes were determined by single‐crystal X‐ray crystallography, which shows that the different metal atoms each have different coordination environments. The zinc atom in ∞3[Zn(S‐2‐N2C4H3)2] exhibits a tetrahedral coordination with one sulfur and three nitrogen atoms from pyrimidinethiolate ligands, whereas the cadmium atoms in ∞2[Cd(S‐2‐N2C4H3)2] and [Cd(S‐2‐N2C4H3)2(tmeda)] are six‐coordinate with either three sulfur and three nitrogen atoms or two sulfur and four nitrogen atoms. In contrast, the mercury atoms in [Hg(S‐2‐N2C4H3)2] display a distorted square‐planar coordination to a pair of chelating –S‐2‐N2C4H3 ligands with additional weak Hg–S interactions to adjacent molecules. While known cadmium and zinc pyrimidinethiolate complexes consist of one‐dimensional chains, ∞3[Zn(S‐2‐N2C4H3)2] and ∞2[Cd(S‐2‐N2C4H3)2] form either three‐ or two‐dimensional polymeric networks of metal atoms. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

  DOI：

  10.1002/ejic.200500253
• 作为产物：
  描述：

  三甲基氯硅烷 、 2-巯基嘧啶 在 三乙胺 作用下， 以 苯 为溶剂， 反应 168.0h， 以69%的产率得到trimethylsilylated 2-thiopyrimidine
  参考文献：
  名称：

  2-Thiozebularine: base modified nucleoside fully constrained in C3′-endo conformation in solution

  摘要：

  2-硫代嘧啶核糖苷（2-thiozebularine，s2zeb）是通过采用硅基N-糖苷键形成的方法，并利用Lawesson试剂对保护的2-氧代核苷衍生物（zebularine，zeb）进行硫化而合成的。将s2zeb的X射线晶体结构和NMR测定的s2zeb和zeb在溶液中的构象与2-硫代尿苷（s2U）和尿苷（U）的结构进行了比较。在固态中，s2zeb分子采用核糖核苷酸的典型构象：C3'-内旋C2'-外旋的核糖环扭曲类型，N-糖苷键为反式，C4'-C5'之间为顺式。然而，在水溶液中，几乎100％的s2zeb呈现C3'-内旋的核糖环扭曲类型。s2zeb的N构象的种群比zeb高约20％（类似于s2U和U核苷的一对），表明巨大的硫原子对N型核糖构象的稳定具有类似的立体效应。有趣的是，zeb和s2zeb中缺少的4-羰基功能使C3'-内旋构象的种群比U和s2U高约30％，这是由于显著的异构效应。两种效应的加成使得2-硫代嘧啶核糖苷在水溶液中几乎完全限制在C3'-内旋构象中。s2zeb的细胞毒性性质比zebularine要稍弱，对HeLa和K562癌细胞以及HUVEC非癌细胞的IC50> 100 mM。

  DOI：

  10.1135/cccc2011081

文献信息

• Efficient Synthesis of Acyclic Nucleosides by N-Alkylation of Pyrimidine and Purine-bases Using a New Coupling Agent of Cesium Iodide
  作者：Yong Hae Kim、Joong Young Kim、Chun Ho Lee

  DOI：10.1246/cl.1988.1045

  日期：1988.6.5

  Acyclic nucleosides, ((1,3-bis(benzyloxy)-2-propoxy) methyl)-2-thio-pyrimidine, -uracil, -2-thiouracil, and -2-thioadenine, and (2-acetoxyethoxy methyl)-2-thioadenine, -2-thiopyrimidine, -uracil, and -2-thiouracil have been successfully synthesized in good yields by N-alkylations of the bases with the corresponding alkyl-acetate (2) and -chloride (3) using cesium iodide under neutral condition in acetonitrile.

  成功合成了无环核苷，包括((1,3-双(苄氧基)-2-丙氧基)甲基)-2-硫代吡啶、-尿嘧啶、-2-硫代尿嘧啶和-2-硫代腺嘌呤，以及(2-乙酰氧乙氧基甲基)-2-硫代腺嘌呤、-2-硫代吡啶、-尿嘧啶和-2-硫代尿嘧啶，合成方法为在中性条件下，使用碘化铯在乙腈中通过与相应的烷基乙酸酯(2)和烷基氯化物(3)进行N-烷基化反应，获得了良好的产量。
• 2-Thiozebularine: base modified nucleoside fully constrained in C3′-endo conformation in solution
  作者：Katarzyna Ebenryter、Stefan Jankowski、Janina Karolak-Wojciechowska、Andrzej Fruziński、Julia Kaźmierczak-Baranska、Barbara Nawrot、Elzbieta Sochacka

  DOI：10.1135/cccc2011081

  日期：——

  2-Thiopyrimidinone ribofuranoside (2-thiozebularine, s²zeb) was synthesized by the adaptation of silyl method of N-glycosidic bond formation and using thionation of protected 2-oxonucleoside derivative (zebularine, zeb) with Lawesson reagent. The X-ray crystal structure of s²zeb and NMR determined conformations of s²zeb and zeb in solution were compared with structures of 2-thiouridine (s²U) and uridine (U). In the solid state s²zeb molecule adopts conformation typical for ribonucleosides: C3′-endo C2′-exo twist type of ribofuranose pucker, anti of N-glycosidic bond and trans around C4′–C5′ bond. In aqueous solution, however, almost 100% population of s²zeb exhibits C3′-endo ribofuranose pucker. The population of N-conformer of s²zeb is about 20% higher than for zeb (analogously to pair of s²U and U nucleosides) indicating similar influence of steric effect of bulky sulfur atom on stabilization of N-type ribose conformation. Interestingly, the absence of 4-carbonyl function in zeb and s²zeb raises the population of C3′-endo conformation by about 30% in comparison to U and s²U as a result of significant anomeric effect. Additive action of both effects makes the 2-thiozebularine almost fully constrained in C3′-endo conformation in aqueous solution. Cytotoxic properties of s²zeb are less pronounced in comparison to zebularine, with IC₅₀ > 100 mM for HeLa and K562 cancer cells and for HUVEC non-cancerous cells.

  2-硫代嘧啶核糖苷（2-thiozebularine，s2zeb）是通过采用硅基N-糖苷键形成的方法，并利用Lawesson试剂对保护的2-氧代核苷衍生物（zebularine，zeb）进行硫化而合成的。将s2zeb的X射线晶体结构和NMR测定的s2zeb和zeb在溶液中的构象与2-硫代尿苷（s2U）和尿苷（U）的结构进行了比较。在固态中，s2zeb分子采用核糖核苷酸的典型构象：C3'-内旋C2'-外旋的核糖环扭曲类型，N-糖苷键为反式，C4'-C5'之间为顺式。然而，在水溶液中，几乎100％的s2zeb呈现C3'-内旋的核糖环扭曲类型。s2zeb的N构象的种群比zeb高约20％（类似于s2U和U核苷的一对），表明巨大的硫原子对N型核糖构象的稳定具有类似的立体效应。有趣的是，zeb和s2zeb中缺少的4-羰基功能使C3'-内旋构象的种群比U和s2U高约30％，这是由于显著的异构效应。两种效应的加成使得2-硫代嘧啶核糖苷在水溶液中几乎完全限制在C3'-内旋构象中。s2zeb的细胞毒性性质比zebularine要稍弱，对HeLa和K562癌细胞以及HUVEC非癌细胞的IC50> 100 mM。
• Synthesis and Structure of the Group 12 Pyrimidinethiolate Complexes _∞ ³ [Zn(S‐2‐N ₂ C ₄ H ₃ ) ₂ ], _∞ ² [Cd(S‐2‐N ₂ C ₄ H ₃ ) ₂ ], [Hg(S‐2‐N ₂ C ₄ H ₃ ) ₂ ] and[Cd(S‐2‐N ₂ C ₄ H ₃ ) ₂ (tmeda)]
  作者：Andreas Eichhöfer、Gernot Buth

  DOI：10.1002/ejic.200500253

  日期：2005.10

  AbstractThe pyrimidinethiolate complexes ∞3[Zn(S‐2‐N2C4H3)2],∞2[Cd(S‐2‐N2C4H3)2] and [Hg(S‐2‐N2C4H3)2] have been prepared by reaction of MCl2 (M = Zn, Cd, Hg) with 2 equiv. of Me3SiS‐2‐N2C4H3 in organic solvents, whilst [Cd(S‐2‐N2C4H3)2(tmeda)] was obtained by recrystallisation of∞2[Cd(S‐2‐N2C4H3)2] in TMEDA at 40 °C. The structures of the complexes were determined by single‐crystal X‐ray crystallography, which shows that the different metal atoms each have different coordination environments. The zinc atom in ∞3[Zn(S‐2‐N2C4H3)2] exhibits a tetrahedral coordination with one sulfur and three nitrogen atoms from pyrimidinethiolate ligands, whereas the cadmium atoms in ∞2[Cd(S‐2‐N2C4H3)2] and [Cd(S‐2‐N2C4H3)2(tmeda)] are six‐coordinate with either three sulfur and three nitrogen atoms or two sulfur and four nitrogen atoms. In contrast, the mercury atoms in [Hg(S‐2‐N2C4H3)2] display a distorted square‐planar coordination to a pair of chelating –S‐2‐N2C4H3 ligands with additional weak Hg–S interactions to adjacent molecules. While known cadmium and zinc pyrimidinethiolate complexes consist of one‐dimensional chains, ∞3[Zn(S‐2‐N2C4H3)2] and ∞2[Cd(S‐2‐N2C4H3)2] form either three‐ or two‐dimensional polymeric networks of metal atoms. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)