N²-isobutyryl-2'-O-tertbutyldimethylsilyl guanosine | 182007-86-9

• 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: N²-isobutyryl-2'-O-tertbutyldimethylsilyl guanosine
• 英文别名: (2)N-isobutyryl-2'O-tertbutyldimethylsilyl guanosine；2'-O-tert-Butyldimethylsilyl-N2-isobutyrylguanosine；N-[9-[(2R,3R,4R,5R)-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 182007-86-9
• 化学式: C₂₀H₃₃N₅O₆Si
• 分子量: 467.597
• InChiKey: HKUCCPHGYWSUOP-XWXWGSFUSA-N

物化性质

• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.36
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  描述：

  N²-isobutyryl-2'-O-tertbutyldimethylsilyl guanosine 在 咪唑 、 四氮唑 、 三氯化磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 49.67h， 生成 (2)N-isobutyryl-2'O-tertbutyldimethylsilyl-3',5'-O-di-(α-cyanoboro-phosphate)-guanosine
  参考文献：
  名称：

  COMPOUNDS FOR TREATING BACTERIAL INFECTIONS

  摘要：

  本发明涉及一类新型鸟嘌呤核苷酸类似物，其抑制RelA和Relseq的合成活性，并具有抗细菌活性。本发明还涉及包括这些化合物的药物组合物，以及利用这些化合物或组合物来对抗细菌和治疗细菌感染的方法。

  公开号：

  US20110086813A1
• 作为产物：
  描述：

  鸟苷 在 咪唑 、 氟化氢吡啶 作用下， 以 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.25h， 生成 N²-isobutyryl-2'-O-tertbutyldimethylsilyl guanosine
  参考文献：
  名称：

  一种有效的制备用于亚磷酰胺RNA合成的受保护核糖核苷的方法

  摘要：

  描述了可用于亚磷酰胺RNA合成的受保护的核糖核苷的有效合成。二吨-butylsilylene组用于和的3'-保护同时核苷的5'位羟基的功能。随后将游离的2'-OH基团进行甲硅烷基化，然后在碱基部分上引入适当的保护，除去环甲硅烷基的保护基团并进行5'-OH的三苯甲基化反应，目标化合物的总收率为60-66％。

  DOI：

  10.1016/s0040-4039(02)00181-8

文献信息

• Synthesis of 2′-<i>O</i>-Substituted Ribonucleosides
  作者：V. Serebryany、L. Beigelman

  DOI：10.1081/ncn-120022724

  日期：2003.10

  efficient synthesis of 2'-O-substituted ribonucleosides, including 2'-O-TBDMS and 2'-O-TOM protected as well as 2'-O-Me and 2'-O-allyl derivatives is presented. Di-t-butylsilylene group was employed for simultaneous protection of 3'- and 5'- hydroxyl functions of nucleoside on the first step. Subsequent silylation or alkylation of free 2'-OH followed by introduction of suitable protection on the base

  提出了2'-O-取代的核糖核苷的有效合成方法，包括2'-O-TBDMS和受保护的2'-O-TOM以及2'-O-Me和2'-O-烯丙基衍生物。第一步，使用二叔丁基亚甲硅烷基同时保护核苷的3'-和5'-羟基官能团。随后将游离的2'-OH进行甲硅烷基化或烷基化，然后在碱基部分上引入合适的保护基，并除去环状甲硅烷基保护基，从而以高收率得到目标化合物。
• ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria
  作者：Ezequiel Wexselblatt、Jehoshua Katzhendler、Raspudin Saleem-Batcha、Guido Hansen、Rolf Hilgenfeld、Gad Glaser、Roee R. Vidavski

  DOI：10.1016/j.bmc.2010.04.064

  日期：2010.6.15

  A prominent feature of the stringent response is the accumulation of two unusual phosphorylated derivatives of GTP and GDP (pppGpp: 5'-triphosphate-3'-diphosphate, and ppGpp: 5'-3'-bis-diphosphate), collectively called (p) ppGpp, within a few seconds after the onset of amino-acid starvation. The synthesis of these 'alarmone' compounds is catalyzed by RelA homologues. Other features of the stringent response include inhibition of stable RNA synthesis and modulation of transcription, replication, and translation. (p) ppGpp accumulation is important for virulence induction, differentiation and antibiotic resistance. We have synthesized a group of (p) ppGpp analogues and tested them as competitive inhibitors of Rel proteins in vitro. 2'-Deoxyguanosine-3'-5'-di(methylene bisphosphonate) [compound (10)] was found as an inhibitor that reduces ppGpp formation in both Gram-negative and Gram-positive bacteria. In silico docking together with competitive inhibition analysis suggests that compound (10) inhibits activity of Rel proteins by competing with GTP/GDP for its binding site.As Rel proteins are completely absent in mammalians, this appears to be a very attractive approach for the development of novel antibacterial agents. (C) 2010 Elsevier Ltd. All rights reserved.
• An efficient preparation of protected ribonucleosides for phosphoramidite RNA synthesis
  作者：Vladimir Serebryany、Leonid Beigelman

  DOI：10.1016/s0040-4039(02)00181-8

  日期：2002.3

  An efficient synthesis of protected ribonucleosides useful for phosphoramidite RNA synthesis is described. Di-t-butylsilylene group was employed for simultaneous protection of 3′- and 5′-hydroxyl functions of nucleoside. Subsequent silylation of free 2′-OH group followed by introduction of suitable protection on the base moiety, removal of cyclic silyl protection and tritylation of 5′-OH gave target

  描述了可用于亚磷酰胺RNA合成的受保护的核糖核苷的有效合成。二吨-butylsilylene组用于和的3'-保护同时核苷的5'位羟基的功能。随后将游离的2'-OH基团进行甲硅烷基化，然后在碱基部分上引入适当的保护，除去环甲硅烷基的保护基团并进行5'-OH的三苯甲基化反应，目标化合物的总收率为60-66％。
• COMPOUNDS FOR TREATING BACTERIAL INFECTIONS
  申请人：Glaser Gad

  公开号：US20110086813A1

  公开（公告）日：2011-04-14

  The present invention relates to a novel class of guanine nucleotide analogs which inhibit RelA and Relseq synthetic activity and which possess anti-bacterial activity. The present invention also relates to pharmaceutical compositions that include such compounds, and to methods of use of such compounds or compositions for combating bacteria and treating bacterial infections.

  本发明涉及一类新型鸟嘌呤核苷酸类似物，其抑制RelA和Relseq的合成活性，并具有抗细菌活性。本发明还涉及包括这些化合物的药物组合物，以及利用这些化合物或组合物来对抗细菌和治疗细菌感染的方法。