5'-azido-2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxyadenosine | 251296-57-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-azido-2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxyadenosine
• 英文别名: 9-[(2R,3R,4R,5R)-5-(azidomethyl)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]oxolan-2-yl]purin-6-amine
• CAS: 251296-57-8
• 化学式: C₂₂H₄₀N₈O₃Si₂
• 分子量: 520.782
• InChiKey: FOZANGPSKPUUFG-WVSUBDOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-azido-2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxyadenosine 在 吡啶 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 2',3'-bis-O-tert-butyldimethylsilyl-5'-deoxy-N6-(ethoxycarbonyl)-5'-[(N-methylcarbamoyl)amino]-adenosine
  参考文献：
  名称：

  合成，SAR，和新颖的抗增殖机理初步评价Ñ 6，5'-双-脲基和5'-氨基甲酰基- ñ 6个-ureidoadenosine衍生物

  摘要：

  我们已经开发了制备有效的方法Ñ 6，5'-双- ureidoadenosine衍生物和它们的5'-氨基甲酰基- ñ 6 -脲基同源。的治疗5'-叠氮基-5'-脱氧Ñ 6 - （ñ -烷基或-arylurea）腺苷衍生物（6A - d）用H 2 /钯-碳或PH 3次/时2 O，随后Ñ -甲基p -nitrophenylcarbamate给ñ 6，5'-双-脲基产品7A - d在49-78％的产率。5'-氨基甲酰基-N 6中的类似衍生物-ureido系列的制备方法是，先用N-甲基-对-硝基苯基氨基甲酸酯处理2'，3'- bis- O -TBS-腺苷（11），然后用适当的异氰酸酯酰化，得到13a - d，产率为45-69％。通过用氯甲酸乙酯处理5' - N-甲基脲基或5'- N-甲基氨基甲酰腺苷衍生物，在55中得到N 6-乙氧羰基衍生物（9和14），从而获得了一种更通用的途径来从这两个系列中获取

  DOI：

  10.1016/j.bmc.2011.11.043
• 作为产物：
  描述：

  5'-氯-5'-脱氧腺苷 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 5'-azido-2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxyadenosine
  参考文献：
  名称：

  A broad spectrum anticancer nucleoside with selective toxicity against human colon cells in vitro

  摘要：

  2',3'-Bis-O-tert-butyldimethylsilyl-5'-deoxy-5'-[N-(methylcarbamoyl)amino]-N-6-(N-phenylcarbamoyl)-adenosine, a new member of the N-6,5'-bis-ureidoadenosine class of anticancer nucleosides, is found to exhibit broad spectrum antiproliferative activity. A majority of the cell lines in the NCI-60 are inhibited with an average GI(50) = 3.13 mu M. Selective toxicity against human colon cancer cell lines (COLO 205, HCC-2998, HCT-116, HT29, KM12) was also exhibited (LC50' s = 6-10 mu M). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.003

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.
• 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.
• Synthesis, SAR, and preliminary mechanistic evaluation of novel antiproliferative N6,5′-bis-ureido- and 5′-carbamoyl-N6-ureidoadenosine derivatives
  作者：Jadd R. Shelton、Christopher E. Cutler、Marcelio Oliveira、Jan Balzarini、Matt A. Peterson

  DOI：10.1016/j.bmc.2011.11.043

  日期：2012.1

  primary alkyl- or arylamines gave the corresponding N6,5′-bis-ureido- or 5′-carbamoyl-N6-ureidoadenosine derivatives in good yields (33–72% and 39–83%; 10a–e and 15a–e, respectively). Significant antiproliferative activities (IC50 ≈ 4–10 μg/mL) were observed for a majority of the N6,5′-bis-ureido derivatives, whereas the 5′-carbamoyl-N6-ureido derivatives were generally less active (IC50 >100 μg/mL). A

  我们已经开发了制备有效的方法Ñ 6，5'-双- ureidoadenosine衍生物和它们的5'-氨基甲酰基- ñ 6 -脲基同源。的治疗5'-叠氮基-5'-脱氧Ñ 6 - （ñ -烷基或-arylurea）腺苷衍生物（6A - d）用H 2 /钯-碳或PH 3次/时2 O，随后Ñ -甲基p -nitrophenylcarbamate给ñ 6，5'-双-脲基产品7A - d在49-78％的产率。5'-氨基甲酰基-N 6中的类似衍生物-ureido系列的制备方法是，先用N-甲基-对-硝基苯基氨基甲酸酯处理2'，3'- bis- O -TBS-腺苷（11），然后用适当的异氰酸酯酰化，得到13a - d，产率为45-69％。通过用氯甲酸乙酯处理5' - N-甲基脲基或5'- N-甲基氨基甲酰腺苷衍生物，在55中得到N 6-乙氧羰基衍生物（9和14），从而获得了一种更通用的途径来从这两个系列中获取
• A broad spectrum anticancer nucleoside with selective toxicity against human colon cells in vitro
  作者：Jadd R. Shelton、Scott R. Burt、Matt A. Peterson

  DOI：10.1016/j.bmcl.2011.01.003

  日期：2011.3

  2',3'-Bis-O-tert-butyldimethylsilyl-5'-deoxy-5'-[N-(methylcarbamoyl)amino]-N-6-(N-phenylcarbamoyl)-adenosine, a new member of the N-6,5'-bis-ureidoadenosine class of anticancer nucleosides, is found to exhibit broad spectrum antiproliferative activity. A majority of the cell lines in the NCI-60 are inhibited with an average GI(50) = 3.13 mu M. Selective toxicity against human colon cancer cell lines (COLO 205, HCC-2998, HCT-116, HT29, KM12) was also exhibited (LC50' s = 6-10 mu M). (C) 2011 Elsevier Ltd. All rights reserved.