2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-[(ethoxycarbonyl)methyl]adenosine | 152965-11-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-[(ethoxycarbonyl)methyl]adenosine
• 英文别名: 2'-O-(tert-butyldimethylsilyl)-3'-[(ethoxycarbonyl)methyl]-3'-deoxyadenosine；ethyl 2-[(2S,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[tert-butyl(dimethyl)silyl]oxy-2-(hydroxymethyl)oxolan-3-yl]acetate
• CAS: 152965-11-2
• 化学式: C₂₀H₃₃N₅O₅Si
• 分子量: 451.598
• InChiKey: SENKOVMSVVEBKY-XBQLXHJASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.26
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-[(ethoxycarbonyl)methyl]adenosine 在 4-二甲氨基吡啶 、 tetramethylguanidinum azide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 5'-azido-2'-O-(tert-butyldimethylsilyl)-3',5'-dideoxy-3'-[(ethoxycarbonyl)methyl]adenosine
  参考文献：
  名称：

  3'-羧甲基-3'-脱氧腺苷衍生物的设计，合成及抗病毒评价

  摘要：

  通过简单有效的方法，由2′-O-TBDMS-3′-[（（乙氧羰基）甲基] -3′-脱氧腺苷（1）制备3′-羧甲基-3′-脱氧腺苷衍生物。通过一种新颖的一锅法，使用5'-活化（TosCl），然后用叠氮化四甲基胍有效地亲核置换，可以将1转化为其5'-叠氮基5'-脱氧衍生物5。使用H2 / Pd-C通过一锅还原/酰化将化合物5转化为5'-[（（N-甲基氨基甲酰基）氨基]衍生物8，然后用对硝基苯基N-甲基氨基甲酸酯处理。通过用苯基异氰酸酯处理引入N 6-苯基氨基甲酰基，并且是一种有效的新方法，用于内酯化2'-O-TBDMS-3'-[（乙氧基羰基）甲基] -3'-脱氧腺苷，得到相应的2'，3'-还开发了内酯。

  DOI：

  10.1080/15257770701426278
• 作为产物：
  描述：

  9-(2,5-di-O-tert-butyldimethylsilyl-β-D-erythro-pentofuran-3-ulosyl)adenosine 在 palladium on activated charcoal 氢气 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-[(ethoxycarbonyl)methyl]adenosine
  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

• Preliminary SAR analysis of novel antiproliferative N6,5′-bis-ureidoadenosine derivatives
  作者：Matt A. Peterson、Marcelio Oliveira、Michael A. Christiansen、Christopher E. Cutler

  DOI：10.1016/j.bmcl.2009.09.083

  日期：2009.12

  A preliminary library of novel N-6,5'-bis-ureidoadenosine analogs and related derivatives was prepared and tested for activity against the NCI 60 panel of human cancers. A 2'-O-TBS group was found to be necessary, but not sufficient, for optimal antiproliferative activity. Neither the N-6-nor 5'-ureido substituents were sufficient to achieve significant antiproliferative effects when present in the absence of the other. The 2'-O-TBS, and N-6,5'-bis-ureido substitution patterns were found to be necessary for optimal antiproliferative activity. (C) 2009 Elsevier Ltd. All rights reserved.
• WO2008/151024
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.
• Design, Synthesis, and Antiviral Evaluation of Some 3′-Carboxymethyl-3′-Deoxyadenosine Derivatives
  作者：Matt A. Peterson、Pucheng Ke、Houguang Shi、Carl Jones、Brenda R. McDougall、W. Edward Robinson

  DOI：10.1080/15257770701426278

  日期：2007.6.15

  3′-Carboxymethyl-3′-deoxyadenosine derivatives were prepared from 2′-O-TBDMS-3′-[(ethoxycarbonyl)methyl]-3′-deoxyadenosine (1) via simple and efficient procedures. Conversion of 1 to its 5′-azido-5′-deoxy derivative 5 was accomplished via a novel one-pot method employing 5′-activation (TosCl) followed by efficient nucleophilic displacement with tetramethylguanidinium azide. Compound 5 was converted

  通过简单有效的方法，由2′-O-TBDMS-3′-[（（乙氧羰基）甲基] -3′-脱氧腺苷（1）制备3′-羧甲基-3′-脱氧腺苷衍生物。通过一种新颖的一锅法，使用5'-活化（TosCl），然后用叠氮化四甲基胍有效地亲核置换，可以将1转化为其5'-叠氮基5'-脱氧衍生物5。使用H2 / Pd-C通过一锅还原/酰化将化合物5转化为5'-[（（N-甲基氨基甲酰基）氨基]衍生物8，然后用对硝基苯基N-甲基氨基甲酸酯处理。通过用苯基异氰酸酯处理引入N 6-苯基氨基甲酰基，并且是一种有效的新方法，用于内酯化2'-O-TBDMS-3'-[（乙氧基羰基）甲基] -3'-脱氧腺苷，得到相应的2'，3'-还开发了内酯。
• 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。