2-N-isobutyryl-3'-O-tert-butyldiphenylsilyl-2'-deoxyguanosine | 114745-19-6

• 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-N-isobutyryl-3'-O-tert-butyldiphenylsilyl-2'-deoxyguanosine
• 英文别名: N2-isobutyryl-3-O'-tert-butyldiphenylsilyl-2'-deoxyguanosine；N-[9-[(2R,4S,5R)-4-[tert-butyl(diphenyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 114745-19-6
• 化学式: C₃₀H₃₇N₅O₅Si
• 分子量: 575.74
• InChiKey: WGHJJYHCMKGYSW-RBZQAINGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-N-isobutyryl-3'-O-tert-butyldiphenylsilyl-2'-deoxyguanosine 在 吡啶 、 N-碘代丁二酰亚胺 、 四丁基氟化铵 、 水 、 potassium carbonate 、 二甲基亚砜 、 四乙基碳酸氢铵 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 甲胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 2'-deoxy-4'-methoxyguanosine
  参考文献：
  名称：

  嘌呤4'-烷氧基-2'-脱氧核苷的直接合成：混合嘌呤-嘧啶4'-烷氧基寡聚脱氧核苷酸作为新的RNA模仿物的首次报道。

  摘要：

  通过N-碘代琥珀酰亚胺促进的烷氧基化，水解和还原反应，然后转化为亚磷酰胺单体进行固相分三步，由核苷4'-5'-烯醇乙酸酯高效地制备了嘌呤和嘧啶4'-烷氧基-2'-脱氧核苷寡核苷酸的合成。以普遍的N型（RNA样）构象为特征的经过完全修饰的4'-烷氧基寡聚脱氧核苷酸表现出优异的化学和核酸酶抗性以及出色的杂交特性，具有很强的RNA选择性杂交趋势，表明其潜在的应用前景。反义技术中的4'-烷氧基-寡脱氧核苷酸。

  DOI：

  10.1021/acs.orglett.5b01430
• 作为产物：
  描述：

  N2-异丁酰-5'-O-(4,4'-二甲氧基三苯基)-2'-脱氧鸟苷 在 咪唑 、 三氯乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 2-N-isobutyryl-3'-O-tert-butyldiphenylsilyl-2'-deoxyguanosine
  参考文献：
  名称：

  Synthesis of 5'-O-Amino-2'-Deoxypyrimidine and Purine Nucleosides: Building-Blocks for Antisense Oligonucleotides

  摘要：

  An efficient synthesis of 5'-O-amino-2'-deoxy analogs of uridine 1, thymidine 2, cytidine 3, 5-methylcytidine 3a, adenosine 4, and guanosine 5 was accomplished. The key step of 5'-O-N-bond formation in 2'-deoxynucleosides 1-5 was achieved via a Mitsunobu reaction in excellent yields. The 5'-O-amino nucleosides 1-5 are useful building-blocks for the synthesis of nucleoside dimers linked by a methylene(methylimino) (MMI) bridge. MMI is a novel phosphate surrogate for antisense oligonucleosides.

  DOI：

  10.1021/jo00121a037

文献信息

• Selective Cleavage of O-(Dimethoxytrityl) Protecting Group with Sodium Periodate
  作者：Dominik Rejman、Šárka Králíková、Zdeněk Točík、Radek Liboska、Ivan Rosenberg

  DOI：10.1135/cccc20020502

  日期：——

  Sodium periodate in aqueous organic solvents selectively removes, under mild reaction conditions, the O-(dimethoxytrityl) protecting group. Selectivity of the cleavage was studied using the nucleoside derivatives protected by various types of groups commonly used in nucleoside and nucleotide chemistry.

  在水有机溶剂中，过碘酸钠在温和的反应条件下选择性地去除了O-(二甲氧基三苯甲基)保护基团。利用核苷衍生物进行了裂解的选择性研究，这些核苷衍生物受到核苷和核苷酸化学中常用的各种基团的保护。
• Preparation of nucleoside 5′-deoxy-5′-methylenephosphonates as building blocks for the synthesis of methylenephosphonate analogues
  作者：Annika Kers、Tomas Szabó、Jacek Stawinski

  DOI：10.1039/a906066i

  日期：——

  Efficient synthesis of suitably protected 2′-deoxycytidine, 2′-deoxyadenosine, and 2′-deoxyguanosine derivatives bearing the 5′-methylenephosphonate moiety with the 4-methoxy-1-oxido-2-picolyl function as an intramolecular nucleophile catalytic group is described.

  本文描述了适当保护2-脱氧胞苷、2-脱氧腺苷和2-脱氧鸟苷衍生物的高效合成，这些衍生物带有5-亚甲基膦酸基团和4-甲氧基-1-氧代-2-皮考林基官能团，作为分子内亲核催化基团。
• Development of a new synthetic method for oligodeoxynucleotides using 3′-<i>H</i>-phosphonamidate derivatives
  作者：Taiki Tsurusaki、Kazuki Sato、Takeshi Wada

  DOI：10.1039/d2ob02292c

  日期：——

  In this study, we developed a new approach for the solution-phase synthesis of oligodeoxynucleotides (ODNs) using nucleoside 3′-H-phosphonamidate derivatives as monomers. The H-phosphonamidate monomers having a heterocyclic amino group as the leaving group reacted with an alcohol to form an internucleotidic H-phosphonate diester under mild basic conditions without using additives. The resultant internucleotidic

  在这项研究中，我们开发了一种使用核苷 3'- H-膦酰胺酸酯衍生物作为单体的溶液相合成寡脱氧核苷酸 (ODN) 的新方法。在不使用添加剂的温和碱性条件下，具有杂环氨基作为离去基团的H-膦酰胺酸酯单体与醇反应形成核苷酸间H-膦酸酯二酯。所得的核苷酸间键被转化为更稳定的键，例如S-氰乙基硫代磷酸二酯。此外，在脱三苯甲基的条件下，未反应的H-膦酰胺酯单体被转化为水溶性化合物，很容易通过萃取去除。因此，只需要简单的萃取来纯化中间体，并且仅用一次硅胶柱层析纯化就实现了从单体到三胸苷二硫代磷酸酯的液相合成。该方法适用于脱氧腺苷、脱氧胞苷和脱氧鸟苷衍生物。这种策略使我们能够减少试剂的数量并简化纯化过程。
• Nucleoside 5′-C-phosphonates: reactivity of the α-hydroxyphosphonate moiety
  作者：Šárka Králíková、Miloš Buděšínký、Milena Masojídková、Ivan Rosenberg

  DOI：10.1016/j.tet.2006.03.008

  日期：2006.5

  We found that various dialkyl phosphites, dialkyl trimethylsilyl phosphites, and tris-trimethylsilyl phosphite reacted smoothly with nucleoside 5'-aldehydes to afford epimeric nucleoside 5'-C-phosphonates in high yields. A number of these compounds in both the 2'-deoxyribo and ribo series were prepared. In the case of 2'-deoxythymidine-5'-aldehyde, a thorough study was made on the influence of the 5'-hydroxyl protecting group, type of phosphite, base, and solvent, on the yield and epimeric ratio of the resulting 5'-hydroxyphosphonates. Partial stereoselectivity in favour of either R or S epimers was observed. An attempt to transform the alpha-hydroxyl of the phosphonate moiety into a halo or azido moiety was not Successful. Only intramolecular substitution reaction of the mesyloxy group for an alkoxy residue of the 2-hydroxyethyl ester took place in a low yield. (c) 2006 Elsevier Ltd. All rights reserved.
• In Vitro and in Vivo Activities of Oligodeoxynucleotide-Based Thrombin Inhibitors Containing Neutral Formacetal Linkages
  作者：Gong-Xin He、John P. Williams、Michael J. Postich、S. Swaminathan、Regan G. Shea、Terry Terhorst、Veronica S. Law、Cheri T. Mao、Cathy Sueoka、Steven Coutré、Norbert Bischofberger

  DOI：10.1021/jm970766i

  日期：1998.10.1

  A series of 15-mer oligodeoxynucleotide analogues were synthesized, and their thrombin inhibitory activities in vitro and in vivo were evaluated. These oligodeoxynucleotide analogues share the same sequence (GGTTGGTGTGGTTGG) but have one or more phosphodiester linkages replaced by a neutral formacetal group. The results obtained from monosubstitutions show that no single phosphodiester group is critical for the thrombin inhibitory activity, suggesting that the interaction between the oligodeoxynucleotide and thrombin is based on a multiple-site charge-charge interaction. Analysis of the effects of different phosphodiester replacements indicates that the backside and left side of the chairlike structure formed by the molecule may be involved in binding with thrombin, presumably by having direct contacts with the anion-binding exosite of the enzyme. For the oligodeoxynucleotides containing two noncontiguous formacetal groups, the effect of the disubstitution is the sum of the effects obtained from the corresponding two monosubstitutions. Infusion of an oligodeoxynucleotide containing four formacetal groups into monkeys showed an increased in vivo anticoagulant effect and an extended in vivo half-life compared to the unmodified oligodeoxynucleotide.