1-(3,5-Di-O-(tert-butyldimethylsilyl)-2-deoxy-β-D-threo-pentofuranosyl)thymine | 142405-90-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(3,5-Di-O-(tert-butyldimethylsilyl)-2-deoxy-β-D-threo-pentofuranosyl)thymine
• 英文别名: TBDMS(-3)[TBDMS(-5)]2-deoxy-D-thrPenf(b)-thymin-1-yl；1-[(2R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 142405-90-1
• 化学式: C₂₂H₄₂N₂O₅Si₂
• 分子量: 470.757
• InChiKey: DDLOCFSZSYGOPG-KZNAEPCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  胸腺嘧啶 在 N-溴代丁二酰亚胺(NBS) 、 4 A molecular sieve 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.33h， 生成 1-(3,5-Di-O-(tert-butyldimethylsilyl)-2-deoxy-β-D-threo-pentofuranosyl)thymine
  参考文献：
  名称：

  Stereoselective Synthesis of 2'-Deoxy-.beta.-D-threo-pentofuranosyl Nucleosides by the NBS-Promoted Coupling Reaction of Thioglycosides with Silylated Heterocyclic Bases

  摘要：

  The NBS-promoted coupling reaction of phenyl 3,5-O-isopropylidene-2-deoxy-1-thio-alpha-D-threo-pentofuranoside (5e) with silylated pyrimidine bases was found to proceed in a highly stereoselective manner (alpha:beta = 1:24-0:1) to afford 2'-deoxy-beta-D-threo-pentofuranosyl pyrimidine nucleosides in satisfactory yields. The highly stereoselective outcome is thought to result from an in situ anomerization-type mechanism, in which intimate ionic intermediates would be in equilibrium and anomerize to the sterically preferable a form. A subsequent S(N)2 type attack to the intermediate will lead to the beta-nucleosides. By using this method, the synthesis of L-nucleosides, 1-(2-deoxy-beta-L-threo-pentofuranosyl)thymine and cytosine derivatives, was also demonstrated by starting from the L-enantiomer of the thioglycoside. On the other hand, the reaction with purine bases was accompanied by the production of undesirable N-7 regioisomers besides the desired N-9 products. The product distribution of the regioisomers was, however, proved to change with reaction time. For instance, a long reaction period allowed the thermodynamically stable N-9 isomers to be exclusively produced with moderate selectivity (alpha:beta = 1:2-1:4.8). The isolated yields of the 9-beta isomers after purification were acceptable for practical use.

  DOI：

  10.1021/jo00104a020

文献信息

• β-Selective synthesis of 2'-deoxynucleosides by the coupling of 2-deoxy-1-thio-D-threo-pentofuranosides with silylated thymine
  作者：Hideyuki Sugimura、Keiko Sujino、Kenji Osumi

  DOI：10.1016/s0040-4039(00)92229-9

  日期：1992.4

  The coupling of the 3,5-O-isopropylidene derivative of phenyl 2-deoxy-1-thio-D-threo-pentofuranoside with silylated thymine in the presence of N-bromosuccinimide yielded 1-(2-deoxy-beta-D-threo-pentofuranosyl)thymine with highly anomeric selectivity.
• Stereoselective Synthesis of 2'-Deoxy-.beta.-D-threo-pentofuranosyl Nucleosides by the NBS-Promoted Coupling Reaction of Thioglycosides with Silylated Heterocyclic Bases
  作者：Hideyuki Sugimura、Kenji Osumi、Yasuko Kodaka、Keiko Sujino

  DOI：10.1021/jo00104a020

  日期：1994.12

  The NBS-promoted coupling reaction of phenyl 3,5-O-isopropylidene-2-deoxy-1-thio-alpha-D-threo-pentofuranoside (5e) with silylated pyrimidine bases was found to proceed in a highly stereoselective manner (alpha:beta = 1:24-0:1) to afford 2'-deoxy-beta-D-threo-pentofuranosyl pyrimidine nucleosides in satisfactory yields. The highly stereoselective outcome is thought to result from an in situ anomerization-type mechanism, in which intimate ionic intermediates would be in equilibrium and anomerize to the sterically preferable a form. A subsequent S(N)2 type attack to the intermediate will lead to the beta-nucleosides. By using this method, the synthesis of L-nucleosides, 1-(2-deoxy-beta-L-threo-pentofuranosyl)thymine and cytosine derivatives, was also demonstrated by starting from the L-enantiomer of the thioglycoside. On the other hand, the reaction with purine bases was accompanied by the production of undesirable N-7 regioisomers besides the desired N-9 products. The product distribution of the regioisomers was, however, proved to change with reaction time. For instance, a long reaction period allowed the thermodynamically stable N-9 isomers to be exclusively produced with moderate selectivity (alpha:beta = 1:2-1:4.8). The isolated yields of the 9-beta isomers after purification were acceptable for practical use.