2-amino-9-[2-(tert-butyldimethylsilyloxy)ethoxymethyl]-1,9-dihydropurin-6-one | 139767-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-amino-9-[2-(tert-butyldimethylsilyloxy)ethoxymethyl]-1,9-dihydropurin-6-one
• 英文别名: 9-[(2-tert-butyldimethylsilyloxyethoxy)methyl]guanine；2'-O-(tert-butyldimethylethylsilyl)acycloguanosine；2-amino-9-[2-[tert-butyl(dimethyl)silyl]oxyethoxymethyl]-1H-purin-6-one
• CAS: 139767-68-3
• 化学式: C₁₄H₂₅N₅O₃Si
• 分子量: 339.47
• InChiKey: UMHOQCWZXOSSCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-9-[2-(tert-butyldimethylsilyloxy)ethoxymethyl]-1,9-dihydropurin-6-one 在 三乙烯二胺 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 9.5h， 生成 [2-amino-9-(2-hydroxyethoxymethyl)-9H-purin-6-yloxy]acetic acid ethyl ester
  参考文献：
  名称：

  Polar, functionalized guanine-O6 derivatives resistant to repair by O6-alkylguanine–DNA alkyltransferase: implications for the design of DNA-modifying drugs

  摘要：

  The protein O6-alkylguanine-DNA alkyltransferase (Atase) is responsible for the repair of DNA lesions generated by several clinically important anti-cancer drugs; this is manifest as active resistance in those cancer cell lines proficient in Atase expression. Novel O6-substituted guanine analogues have been synthesized, bearing acidic, basic and hydrogen bonding functional groups. In contrast to existing O6-modified purine analogues, such as methyl or benzyl, the new compounds were found to resist repair by Atase even when tested at concentrations much higher than O6-benzylguanine, a well-established Atase substrate active both in vitro and in vivo. The inactivity of the new purines as covalent substrates for Atase indicates that agents to deliver these groups to DNA would represent a new class of DNA-modifying drug that circumvents Atase-mediated resistance. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2005.11.007
• 作为产物：
  描述：

  鸟嘌呤 在 咪唑 、 三氟甲磺酸 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 2-amino-9-[2-(tert-butyldimethylsilyloxy)ethoxymethyl]-1,9-dihydropurin-6-one
  参考文献：
  名称：

  阿昔洛韦及其各种前药的区域选择性合成

  摘要：

  9-[(2-羟基乙氧基) 甲基] 鸟嘌呤（阿昔洛韦1，方案1）的高产区域选择性合成是从鸟嘌呤通过三甲硅烷基化鸟嘌呤实现的。N 2-acylacyclovir 9a-9b 由 N 2, O-diacylacyclovir (4, 8b-8d) 使用区域选择性脱酰程序制备。N 2-无环鸟苷11和13通过伯羟基的保护制备。阿昔洛韦的三种氨基酸酯合成为水溶性前药，在 pH 7.4 磷酸盐缓冲液中形成质子化阳离子。还合成了两种具有游离羧酸的水溶性酯前药，它们在 pH 7.4 的磷酸盐缓冲液中形成阴离子物质。方案 1. 试剂和条件： i．乙酸酐，HOAc，DMAP，160°C，8小时，3：88%；ii. P-TsOH、1,3-二氧戊环、Ac2O、HOAc；然后，甲苯，回流，1小时，4：18%；5：2.3%；4和5：52%；三、40% CH3NH2水溶液，1:93%。

  DOI：

  10.1081/scc-100104050

文献信息

• Demonstration of an Alternative Mechanism for <b>G-to-G </b>Cross-Link Formation
  作者：Ming Qian、Rainer Glaser

  DOI：10.1021/ja045108j

  日期：2005.1.1

  cyanoamine derivative. Thus, all known products of nitrosative guanine deamination are consistent with the postulate of pyrimidine ring-opening. This postulated mechanism not only explains what is already known but also suggests that other products and other cross-links also might be formed in DNA deamination. The study suggests one possible new product: the structure isomer aG(N1)-to-rG(C2) of the classical

  dG 到 dG 的交联是 DNA 亚硝化的重要产物。它的形成通常归因于鸟嘌呤对鸟嘌呤重氮离子中 N2 的亲核取代，而最近的研究表明鸟嘌呤加成到去重氮、去质子化和嘧啶开环后形成的氰胺衍生物中。后一种机制的化学可行性在这里得到了通过 rG 添加到合成氰胺衍生物的 rG 到 aG 形成的实验证明的支持。因此，所有已知的亚硝化鸟嘌呤脱氨基产物都与嘧啶开环假设一致。这种假定的机制不仅解释了已知的内容，而且表明在 DNA 脱氨作用中也可能形成其他产物和其他交联。该研究提出了一种可能的新产品：经典 G(N2)-G(C2) 交联的结构异构体 aG(N1)-to-rG(C2)。虽然 aG(N2) 到 rG(C2) 的形成是通过化学合成确定的，但结构异构体 aG(N1) 到 rG(C2) 已根据其 MS/MS 谱暂时指定，因为这从机械的角度来看，分配是合理的。密度泛函计算显示了经典交联 G(N2)-G(C2)
• REGIOSELECTIVE SYNTHESIS OF ACYCLOVIR AND ITS VARIOUS PRODRUGS
  作者：Hongwu Gao、Ashim K. Mitra

  DOI：10.1081/scc-100104050

  日期：2001.1

  High-yield regioselective synthesis of 9-[(2-hydroxyethoxy) methyl]guanine (Acyclovir 1, Scheme 1) was achieved from guanine via trisilylated guanine. N 2-acylacyclovir 9a–9b were prepared from N 2, O-diacylacyclovir (4, 8b–8d) using regioselective deacylation procedure. N 2- Acylacyclovir 11 and 13 were prepared via protection of primary hydroxyl groups. Three amino acid esters of acyclovir were synthesized

  9-[(2-羟基乙氧基) 甲基] 鸟嘌呤（阿昔洛韦1，方案1）的高产区域选择性合成是从鸟嘌呤通过三甲硅烷基化鸟嘌呤实现的。N 2-acylacyclovir 9a-9b 由 N 2, O-diacylacyclovir (4, 8b-8d) 使用区域选择性脱酰程序制备。N 2-无环鸟苷11和13通过伯羟基的保护制备。阿昔洛韦的三种氨基酸酯合成为水溶性前药，在 pH 7.4 磷酸盐缓冲液中形成质子化阳离子。还合成了两种具有游离羧酸的水溶性酯前药，它们在 pH 7.4 的磷酸盐缓冲液中形成阴离子物质。方案 1. 试剂和条件： i．乙酸酐，HOAc，DMAP，160°C，8小时，3：88%；ii. P-TsOH、1,3-二氧戊环、Ac2O、HOAc；然后，甲苯，回流，1小时，4：18%；5：2.3%；4和5：52%；三、40% CH3NH2水溶液，1:93%。
• Polar, functionalized guanine-O6 derivatives resistant to repair by O6-alkylguanine–DNA alkyltransferase: implications for the design of DNA-modifying drugs
  作者：Dimitrios Pletsas、Richard T. Wheelhouse、Vassiliki Pletsa、Anna Nicolaou、Terence C. Jenkins、Michael C. Bibby、Soterios A. Kyrtopoulos

  DOI：10.1016/j.ejmech.2005.11.007

  日期：2006.3

  The protein O6-alkylguanine-DNA alkyltransferase (Atase) is responsible for the repair of DNA lesions generated by several clinically important anti-cancer drugs; this is manifest as active resistance in those cancer cell lines proficient in Atase expression. Novel O6-substituted guanine analogues have been synthesized, bearing acidic, basic and hydrogen bonding functional groups. In contrast to existing O6-modified purine analogues, such as methyl or benzyl, the new compounds were found to resist repair by Atase even when tested at concentrations much higher than O6-benzylguanine, a well-established Atase substrate active both in vitro and in vivo. The inactivity of the new purines as covalent substrates for Atase indicates that agents to deliver these groups to DNA would represent a new class of DNA-modifying drug that circumvents Atase-mediated resistance. (c) 2006 Elsevier SAS. All rights reserved.