5'-azido-2'-O-(tert-butyldimethylsilyl)-3'-(carboxymethyl)-3',5'-dideoxyuridine | 251296-78-3

• 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: 5'-azido-2'-O-(tert-butyldimethylsilyl)-3'-(carboxymethyl)-3',5'-dideoxyuridine
• 英文别名: 5'-azido-2'-O-tert-butyldimethylsilyl-3',5'-dideoxy-3'-carboxymethyluridine；2-[(2S,3R,4R,5R)-2-(azidomethyl)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)oxolan-3-yl]acetic acid
• CAS: 251296-78-3
• 化学式: C₁₇H₂₇N₅O₆Si
• 分子量: 425.517
• InChiKey: AVFYEJOXHMKDBF-YIKOMLBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.23
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5'-azido-2'-O-(tert-butyldimethylsilyl)-3'-(carboxymethyl)-3',5'-dideoxyuridine 在 palladium on activated charcoal 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 20.0 ℃ 、34.47 kPa 条件下， 反应 8.0h， 生成 5'-amino-2'-O-(tert-butyldimethylsilyl)-3'-[[N-(2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxyuridin-5'-yl)carbamoyl]methyl]-3',5'-dideoxyuridine
  参考文献：
  名称：

  Amide-Linked Ribonucleoside Dimers Derived from 5‘-Amino-5‘-deoxy- and 3‘-(Carboxymethyl)-3‘-deoxynucleoside Precursors¹

  摘要：

  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.

  DOI：

  10.1021/jo9908647
• 作为产物：
  描述：

  1-[2,5-bis-O-(tert-butyldimethylsilyl)-3-deoxy-3-(ethoxycarbonyl)methylene-β-D-ribofuranosyl]uracil 在 palladium on activated charcoal sodium hydroxide 、 sodium azide 、 水 、 氢气 、 碘 、 三苯基膦 、 三氟乙酸 作用下， 以 吡啶 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 65.0 ℃ 、34.47 kPa 条件下， 反应 87.0h， 生成 5'-azido-2'-O-(tert-butyldimethylsilyl)-3'-(carboxymethyl)-3',5'-dideoxyuridine
  参考文献：
  名称：

  Amide-Linked Ribonucleoside Dimers Derived from 5‘-Amino-5‘-deoxy- and 3‘-(Carboxymethyl)-3‘-deoxynucleoside Precursors¹

  摘要：

  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.

  DOI：

  10.1021/jo9908647

文献信息

• Synthesis, biophysical studies and RNA interference activity of RNA having three consecutive amide linkages
  作者：Paul Tanui、Scott D. Kennedy、Benjamin D. Lunstad、Amanda Haas、Devin Leake、Eriks Rozners

  DOI：10.1039/c3ob42532k

  日期：——

  RNA sequences having up to three consecutive internal amide linkages were synthesized and studied using UV and NMR spectroscopy. The amide modifications did not interfere with normal base-pairing and A-type RNA conformation. Three consecutive amides were well tolerated in the passenger strand of siRNA and caused little change in RNAi activity.

  合成具有多达三个连续内部酰胺键的 RNA 序列，并使用 UV 和 NMR 光谱进行研究。酰胺修饰不会干扰正常的碱基配对和 A 型 RNA 构象。三个连续的酰胺在 siRNA 的过客链中具有良好的耐受性，并且几乎没有引起 RNAi 活性的变化。
• Toward Amide-Linked RNA Mimics:  Total Synthesis of 3‘-C Branched Uridine Azido Acid via an Ene−Iodolactonization Approach
  作者：Eriks Rozners、Yang Liu

  DOI：10.1021/ol027229z

  日期：2003.1.1

  novel synthesis of 3'-C branched uridine azido acid has been accomplished by a sequence of stereoselective ene and iodolactonization reactions. Compared to traditional routes that start from carbohydrates, the present methodology is more flexible and can be further optimized by incorporation of novel future developments of synthetic chemistry. Because the key chemistry does not involve the 3'-C substituent

  [反应：见正文] 3'-C支链尿苷叠氮酸的新颖合成已通过一系列立体选择性烯和碘内酯化反应完成。与从碳水化合物开始的传统路线相比，本方法学更加灵活，可以通过纳入合成化学的新的未来发展而进一步优化。因为关键化学反应不涉及3'-C取代基，所以我们的方法是制备3'-C烷基核苷类似物的通用方法。
• Synthesis of Amide-Linked [(3′)CH₂CO-NH(5′)] Nucleoside Analogues of Small Oligonucleotides
  作者：Morris J. Robins、Bogdan Doboszewski、Bradley L. Nilsson、Matt A. Peterson

  DOI：10.1080/15257770008032997

  日期：2000.1

  We report syntheses of new amide-linked (di-penta)nucleoside analogues of antisense oligonucleotide components. Solution-phase coupling of 3'-(carboxymethyl)-3'-deoxy- and 5'-amino-5'-deoxynucleoside derivatives provides amide dimers. Activated [3'-(carboxymethyl)-3'-deoxy] units with a 5'-azido-5'-deoxy function provide "masked" 5'-amino-5'-deoxy residues for chain extension, and a 5'-O-DMT-protected

  我们报告了反义寡核苷酸组件的新的酰胺连接的（二戊）核苷类似物的合成。3'-（羧甲基）-3'-脱氧-和5'-氨基-5'-脱氧核苷衍生物的溶液相偶联提供了酰胺二聚体。具有5'-叠氮基-5'-脱氧功能的活化的[3'-（羧甲基）-3'-脱氧]单元提供“被屏蔽的” 5'-氨基-5'-脱氧残基用于链延伸，以及5'- O-DMT保护的单元提供了5'末端以连接至磷酸二酯键。
• 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.