2',5'-bis-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-[(ethoxycarbonyl)methyl]uridine | 178985-82-5

• 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: 2',5'-bis-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-[(ethoxycarbonyl)methyl]uridine
• 英文别名: 1-[2,5-bis-O-(tert-butyldimethylsilyl)-3-deoxy-3-α-(ethoxycarbonyl)methyl-β-D-ribofuranosyl]uracil；ethyl 2-[(2S,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-(2,4-dioxopyrimidin-1-yl)oxolan-3-yl]acetate
• CAS: 178985-82-5
• 化学式: C₂₅H₄₆N₂O₇Si₂
• 分子量: 542.82
• InChiKey: KMSHCFXVLMNYMP-MCEIDBOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.42
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2',5'-bis-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-[(ethoxycarbonyl)methyl]uridine 在 camphor-10-sulfonic acid 、 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 、 乙腈 为溶剂， 反应 19.5h， 生成 N⁴-benzoyl-1-[2-O-(tert-butyldimethylsilyl)-3-deoxy-3-α-(ethoxycarbonyl)methyl-5-O-(dimethoxytrityl)-β-D-ribofuranosyl]cytosine
  参考文献：
  名称：

  用酰胺键取代锤头状核酶底物的可裂解磷酸二酯键

  摘要：

  已经制备了其中天然磷酸二酯键被等排酰胺键取代的核苷二聚体。该二聚体类似物随后在锤头状核酶底物的裂解位置化学结合。尽管如凝胶阻滞分析所示，所得的底物类似物对核酶表现出高亲和力，但在核酶裂解活性的标准条件下，酰胺键被证明对裂解具有完全的抵抗力。

  DOI：

  10.1002/(sici)1099-0690(200002)2000:4<633::aid-ejoc633>3.0.co;2-u
• 作为产物：
  描述：

  2',5'-bis-O-tert-butyldimethylsilyl-3'-ketouridine 在 10% palladium on active carbon 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、34.48 kPa 条件下， 反应 72.0h， 生成 2',5'-bis-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-[(ethoxycarbonyl)methyl]uridine
  参考文献：
  名称：

  合成2'，3'融合的（3.3.0）γ-丁内酯-核苷并与氨基核苷偶合，得到酰胺连接的核苷酸-二聚体类似物

  摘要：

  易于（通过3'-酮）从2'，5'-双-O-（叔丁基二甲基甲硅烷基）核苷获得的Wittigg产物的立体选择性加氢提供了2'，3'-融合的γ-丁内酯核苷的有效通道与5'-氨基-核苷（2-羟基吡啶催化）偶联，得到酰胺连接的核苷酸-二聚体类似物。

  DOI：

  10.1016/0040-4039(96)00715-0

文献信息

• Synthesis of 2′,3′-fused (3.3.0) γ-butyrolactone-nucleosides and coupling with amino-nucleosides to give amide-linked nucleotide-dimer analogues
  作者：Morris J. Robins、Sanchita Sarker、Meiqiang Xie、Weijian Zhang、Matt A. Peterson

  DOI：10.1016/0040-4039(96)00715-0

  日期：1996.6

  Stereoselective hydrogenation of Wittigg products obtained readily (via the 3′-ketones) from 2′,5′-bis-O-(tert-butyldimethylsilyl)nucleosides provides efficient access to 2′,3′-fused γ-butyrolactone-nucleosides that can be coupled with 5′-amino-nucleosides (2-hydroxypyridine catalysis) to give amide-linked nucleotide-dimer analogues.

  易于（通过3'-酮）从2'，5'-双-O-（叔丁基二甲基甲硅烷基）核苷获得的Wittigg产物的立体选择性加氢提供了2'，3'-融合的γ-丁内酯核苷的有效通道与5'-氨基-核苷（2-羟基吡啶催化）偶联，得到酰胺连接的核苷酸-二聚体类似物。
• Amide-Linked Ribonucleoside Dimers Derived from 5‘-Amino-5‘-deoxy- and 3‘-(Carboxymethyl)-3‘-deoxynucleoside Precursors¹
  作者：Matt A. Peterson、Bradley L. Nilsson、Sanchita Sarker、Bogdan Doboszewski、Weijian Zhang、Morris J. Robins

  DOI：10.1021/jo9908647

  日期：1999.10.1

  Treatment of tert-butyldimethylsilyl (TBDMS) derivatives of 3'-keto(adenosine or uridine) with [(ethoxycarbonyl)methylene]triphenylphosphorane gave exocyclic alkenes that underwent stereoselective hydrogenation to give 3'-deoxy-3'-[(ethoxycarbonyl)methyl](Ado or Urd) analogues. Saponification provided the 3'-(carboxymethyl)-3'-deoxy(Ado and Urd) derivatives 37 and 38. Treatment of 37 or 38 with DCC and 5'-amino-2',3'-bis-O-TBDMS-5'-deoxynucleosides gave the amide-linked dimers (74-82%). Activation of 37 or 38 with 4-nitrophenol/DCC, and direct coupling of the 4-nitrophenyl esters with 5'-amino-5'-deoxy(Ado or Urd) in pyridine also produced amide dimers efficiently (65-70%). Analogous activation of a 5'-O-DMT-protected carboxylate, and its coupling with 5'-amino-5'-deoxy-2'-O-methyladenosine gave the amide dimer in good yield (74%). Coupling (DCC) of a 5'-azido-2'-O-TBDMS-3'-(carboxymethyl)-3', 5'-dideoxyuridine intermediate with 5'-amino-5'-deoxynucleosides gave amide-linked dimers (72-78%) that can serve as masked (azide reduction) 5'-amino dimers for analogous synthesis of extended amide-linked oligomers.
• Replacement of the Cleavable Phosphodiester Bond of a Hammerhead Ribozyme Substrate by an Amide Linkage
  作者：Fabienne Burlina、Alain Favre、Jean-Louis Fourrey、Martial Thomas

  DOI：10.1002/(sici)1099-0690(200002)2000:4<633::aid-ejoc633>3.0.co;2-u

  日期：2000.2

  dimer in which the natural phosphodiester bond is replaced by an isosteric amide linkage has been prepared. This dimer analogue was subsequently incorporated chemically at the cleavage position of a hammerhead ribozyme substrate. Although the resulting substrate analogue exhibited a high affinity for the ribozyme as shown by gel retardation assays, the amide bond proved to be fully resistant to cleavage

  已经制备了其中天然磷酸二酯键被等排酰胺键取代的核苷二聚体。该二聚体类似物随后在锤头状核酶底物的裂解位置化学结合。尽管如凝胶阻滞分析所示，所得的底物类似物对核酶表现出高亲和力，但在核酶裂解活性的标准条件下，酰胺键被证明对裂解具有完全的抵抗力。