3'-甲氧基腺苷 | 10300-22-8

• 物质功能分类: 生物化工 - 核苷类药物 - 核苷中间体
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 3'-甲氧基腺苷
• 英文名称: 3'-O-methyladenosine
• 英文别名: (2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)-4-methoxyoxolan-3-ol
• CAS: 10300-22-8
• 化学式: C₁₁H₁₅N₅O₄
• 分子量: 281.271
• InChiKey: RYAFZRROCNNRFK-IOSLPCCCSA-N

物化性质

• 熔点：
  177-178 °C
• 沸点：
  623.8±65.0 °C(Predicted)
• 密度：
  1.84±0.1 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3'-甲氧基腺苷 在 吡啶 、 2,6-二甲基吡啶 、 四氮唑 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 水 、 碘 、 乙酸肼 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 9.0h， 生成
  参考文献：
  名称：

  完全保护的 2'-5' 寡聚腺苷酸 (2-5A) 的合成和酶促脱保护：针对短 2-5A 的前药策略

  摘要：

  完全保护的 pA2'p5'A2'p5'A 三聚体 1a 和 1b 已分别制备为短的 2'-5' 寡腺苷酸 2-5A 及其 3'-O-Me 类似物的前药候选物。研究了猪肝羧酸酯酶 (HLE) 在 HEPES 缓冲液 (pH 7.5) 中 37° 触发的脱保护的动力学。结果证明 1a 的脱保护非常缓慢，而 2-5A 从未以完全脱保护的形式出现。相比之下，相当一部分 1b 转化为所需的 2-5A 三聚体，尽管在暴露相邻的磷酸二酯键之前部分去除 3'-O-[(乙酰氧基)甲基] 基团导致 2',5' →3',5' 磷酸盐迁移和腺苷释放作为副反应。

  DOI：

  10.1002/cbdv.201100144
• 作为产物：
  描述：

  腺苷 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以27%的产率得到2'-O-甲基腺苷
  参考文献：
  名称：

  Synthesis and conformational analysis of phosphate-methylated RNA dinucleotides

  摘要：

  Synthesis of RNA dimers having a methyl phosphotriester group as the internucleoside linkage is reported; six pairs of diasteroisomerically pure systems were prepared, i.e, r(CpU) (15), r(ApU) (16), r(CpC) (17), r(ApC) (18), r(CpG) (19), and r(ApG) (20). Compounds 15-20 are stabilized by a 2'-O-methyl group in the 5'-terminal residue. The present systems represent the third class of backbone-modified RNA oligomers, following the 2'-O-methylribonucleotide phosphorothioates and the 2'-O-methylribonucleotide methyl phosphonates. Our synthetic approach comprises the use of 9-fluorenylmethoxycarbonyl (Fmoc) groups for transient protection of the exocyclic NH2 groups of the bases A, C, and G, levulinoyl (Lev) groups for the transient protection of the 2'-and 3'-OH groups of the 3'-terminal residues, methanolic K2CO3 for the simultaneous removal of Fmoc and Lev groups with full preservation of the methyl phosphotriester function, and finally reversed-phase HPLC separation of the S(P) and R(P) diastereoisomers. The availability of the six dimers in diastereoisomerically pure form enabled us to examine the molecular conformations using high-field NMR and circular dichroism (CD) spectroscopy. These studies led to the following conclusions: (i) NMR J-coupling analysis: the central C4'-C5' (gamma) and C5'-O5' (beta) bonds in 15-20 show less preference for the gamma+ and beta-t rotamers, in comparison with their natural analogues, i.e., base stacking is diminished upon introduction of the two methyl groups on O2' and on the phosphate methyl groups on O2' and on the phosphate group; (ii) CD analysis: 15-20 show substantially reduced molecular ellipticities when compared to the natural counterparts, which also reveals that base stacking is reduced; (iii) UV and variable-temperature H-1 NMR measurements: (S(P)- and (R(P))-19 show self-association, via the formation of a right-handed miniduplex with two C-G base pairs ((S(P)-19, T(m) = 9.3-degrees-C, concn = 36.6-mu-M; (R(P))-19, T(m) = 8.7-degrees-C, concn = 48.1-mu-M). The present conformational data on (R(P))- and (S(P))-15-20 are in agreement with literature data on other phosphate-triesterified oligonucleotides, e.g., the trimer d(T(POEt)G(POEt)G) and the tetramer d(T(POEt)T(POEt)C(POEt)A). While the latter systems also showed little base-base stacking, it was established that they readily form a local duplex with a complementary natural RNA sequence. Hence we anticipate that phosphate-methylated 2'-O-methyl-RNA oligomers, longer than the dimer systems described in the present work, will also hybridize easily with complementary natural RNA.

  DOI：

  10.1021/jo00020a028
• 作为试剂：
  描述：

  腺苷 、 甲醇 、 diaquatetrachlorotin(IV) 、 重氮甲烷 在 乙醇 、 2'-O-甲基腺苷 、 3'-甲氧基腺苷 作用下， 以 乙二醇二甲醚 为溶剂， 反应 2.0h， 以to give 2'-O-methyladenosine (Compound 1) and 3'-O-methyladenosine (Compound 2)的产率得到2'-O-甲基腺苷
  参考文献：
  名称：

  Novel adenosine derivatives and pharmaceutical composition containing

  摘要：

  公式（I）的新腺苷化合物：##STR1## 其中R.sub.1，R.sub.2和R.sub.3是氢或较低的烷基；X是氢，较低的烷基，氨基或卤素；Y是氢或较低的烷基，表现出作为降压剂的实用性。

  公开号：

  US04843066A1

文献信息

• Selective 2′-<i>O</i>-Methylation of Pyrimidine-Ribonucleosides by Trimethylsulfonium Hydroxide in the Presence of Mg²⁺and Ca²⁺Ions
  作者：Kiyoshi Yamauchi、Toru Nakagima、Masayoshi Kinoshita

  DOI：10.1246/bcsj.59.2947

  日期：1986.9

  Reactions of various ribonucleosides with trimethylsulfonium hydroxide were investigated in the presence of Mg2+ and Ca2+ ions. The 2′-OH groups of pyrimidine-ribonucleosides were methylated selectively.

  在 Mg2+ 和 Ca2+ 离子存在下研究了各种核糖核苷与氢氧化三甲基锍的反应。嘧啶核糖核苷的 2'-OH 基团被选择性甲基化。
• The Methylation of Ribonucleosides by Trimethyl Phosphate or Dimethyl Sulfate in the Presence of Boric Acid
  作者：Yorisato Hisanaga、Toshizumi Tanabe、Kiyoshi Yamauchi、Masayoshi Kinoshita

  DOI：10.1246/bcsj.54.1569

  日期：1981.5

  Uridine, inosine, adenosine, and thymidine were methylated selectively at the base moieties by the use of trimethyl phosphate or dimethyl sulfate in the presence of boric acid. A suppressing effect of boric acid on the methylation of the ribose-hydroxyl groups was discussed briefly.

  在硼酸的存在下，通过使用磷酸三甲酯或硫酸二甲酯，尿苷、肌苷、腺苷和胸苷在碱基部分被选择性甲基化。简要讨论了硼酸对核糖羟基甲基化的抑制作用。
• Improved Synthesis and Isolation of 2′-<i>O</i>-Methyladenosine: Effective and Scalable Enzymatic Separation of 2′/3′-<i>O</i>-Methyladenosine Regioisomers
  作者：Saúl Martínez-Montero、Susana Fernández、Tatiana Rodríguez-Pérez、Yogesh S. Sanghvi、Ke Wen、Vicente Gotor、Miguel Ferrero

  DOI：10.1002/ejoc.200900348

  日期：2009.7

  develop a separation protocol. Upon extraction of the acylated products, the 3′-O-methyladenosine was isolated in 81 % yield and 97 % purity from the aqueous layer. Hydrolysis of acylated products in organic layer furnished 2′-O-methyladenosine in 67 % yield and 99 % purity. The separation process was successfully applied to the crude reaction mixture of methylated products (ca. 3:1 of 1/2) on 5-g scale

  使用固定化洋葱假单胞菌脂肪酶 (PSL-C) 结合乙酰丙酸丙酮肟作为酰基，通过选择性酶促酰化开发了 2'/3'-O-甲基腺苷区域异构体混合物 (1 + 2; 1:1) 的有效分离捐赠者。2'-O-甲基腺苷 (1) 的 3'-羟基以高选择性（约 70%）酰化，而相同溶液中等量的 3'-O-甲基腺苷 (2) 导致轻微酰化5'-羟基（约 8%）。两种区域异构体对酶促酰化的不同行为允许制定分离方案。在萃取酰化产物后，3'-O-甲基腺苷以81%的产率和97%的纯度从水层中分离出来。有机层中酰化产物的水解以 67% 的产率和 99% 的纯度提供了 2'-O-甲基腺苷。该分离过程已成功应用于 5 克规模的甲基化产物（约 3:1 的 1/2）的粗反应混合物。我们还报告了使用对甲苯磺酸甲酯作为腺苷 2'-O-甲基化的安全试剂。（© Wiley-VCH Verlag GmbH & Co. KGaA，69451
• Nucleosides. Part LXI. A Simple Procedure for the Monomethylation of Protected and Unprotected Ribonucleosides in the 2?-O- and 3?-O-Position Using Diazomethane and the Catalyst Stannous Chloride
  作者：Hagen Cramer、Wolfgang Pfleiderer

  DOI：10.1002/hlca.19960790808

  日期：1996.12.11

  Intensive studies on the diazomethane methylation of the common ribonucleosides uridine, cytidine, adenosine, and guanosine and its derivatives were performed to obtain preferentially the 2′-O-methyl isomers. Methylation of 5′-O-(monomethoxytrityl)-N2-(4-nitrophenyl)ethoxycarbonyl-O6-[2-(4-nitrophenyl)ethyl]-guanosine (1) with diazomethane resulted in an almost quantitative yield of the 2′- and 3′-O-methyl

  对常见核糖核苷尿苷，胞苷，腺苷和鸟苷及其衍生物的重氮甲烷甲基化进行了深入研究，以优先获得2'- O-甲基异构体。5'- O-（单甲氧基三苯甲基）-N 2-（4-硝基苯基）乙氧基羰基-O 6- [2-（4-硝基苯基）乙基]-鸟苷（1）的甲基化与重氮甲烷反应，几乎可以定量地得到2可以通过简单的硅胶快速色谱法（方案1）分离的′-和3′- O-甲基异构体。用重氮甲烷甲基化腺苷，胞苷和尿苷，同时保护和不保护5'- O-通过单-或二甲氧基三苯甲基基团的位置-和腺苷和胞苷的苷元部分被2-（4-硝基苯基）乙氧羰基（npeoc）基团（方案2-4）。尝试尽可能多地增加2'- O-甲基异构体的形成是基于各种溶剂，温度，催化剂和甲基化反应过程中催化剂的浓度。
• 2-5A ANALOGS AND THEIR METHODS OF USE
  申请人：Beigelman Leonid

  公开号：US20100331397A1

  公开（公告）日：2010-12-30

  Disclosed herein are compounds that activate RNaseL, methods of synthesizing compounds that activate RNaseL and the use of compounds that activate RNaseL for treating and/or ameliorating a disease or a condition, such as a viral infection, a bacterial infection, cancer and/or parasitic disease.

  本文披露了激活RNaseL的化合物，合成激活RNaseL的化合物的方法，以及利用激活RNaseL的化合物治疗和/或改善疾病或状况的用途，例如病毒感染、细菌感染、癌症和/或寄生虫病。