4(R)-(6-amino-9H-purin-9-yl)-2(R)-(hydroxymethyl)tetrahydrofuran-3(S)-ol | 64395-31-9

• 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: 4(R)-(6-amino-9H-purin-9-yl)-2(R)-(hydroxymethyl)tetrahydrofuran-3(S)-ol
• 英文别名: 2-C-(adenin-9-yl)-1,4-anhydro-2-deoxy-D-arabino-pentitol；(2R)-2-C-(adenine-9-yl)-1,4-anhydro-2-deoxy-D-arabitol；(2R)-2-C-(adenin-9-yl)-1,4-anhydro-2-deoxy-D-arabitol；2'-isodeoxyadenosine；2-(6-amino-purin-9-yl)-D-1,2-dideoxy-arabinofuranose；(2R,3S,4R)-4-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 64395-31-9
• 化学式: C₁₀H₁₃N₅O₃
• 分子量: 251.245
• InChiKey: XLAFLMYNXDUGLH-JKMUOGBPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4(R)-(6-amino-9H-purin-9-yl)-2(R)-(hydroxymethyl)tetrahydrofuran-3(S)-ol 生成 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furan methanol
  参考文献：
  名称：

  Ohrui, Hiroshi; Waga, Toshiaki; Meguro, Hiroshi, Bioscience, Biotechnology and Biochemistry, 1993, vol. 57, # 6, p. 1040 - 1042

  摘要：

  DOI：
• 作为产物：
  描述：

  [(3aR,4R,6aS)-2,2-dioxo-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3,2]dioxathiol-4-yl]methoxy-tert-butyl-diphenylsilane 在 盐酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 22.5h， 生成 4(R)-(6-amino-9H-purin-9-yl)-2(R)-(hydroxymethyl)tetrahydrofuran-3(S)-ol
  参考文献：
  名称：

  异构核苷的新通用合成

  摘要：

  描述了一种有效的合成异核苷的新方法。合成中的关键步骤是嘌呤和嘧啶碱基与碳水化合物中间体的环状硫酸盐直接偶联。该反应以高区域专一性和立体专一性进行。

  DOI：

  10.1016/s0040-4039(01)01118-2

文献信息

• Nucleosides and nucleotides. 132. Synthesis and biological evaluations of ring-expanded oxetanocin analogues: Purine and pyrimidine analogues of 1,4-anhydro-2-deoxy-d-arabitol and 1,4-anhydro-2-deoxy-3-hydroxymethyl-d-arabitol
  作者：Akio Kakefuda、Satoshi Shuto、Takemitsu Nagahata、Jun-ichi Seki、Takuma Sasaki、Akira Matsuda

  DOI：10.1016/s0040-4020(01)81749-x

  日期：1994.8

  (2R)-2-C-(Adenin-9-yl)-1,4-anhydro-2-deoxy-D-arabitol (2) and (2R, 3R)-2-C-(adenin-9-yl)-1,4-anhydro-2,3-dideoxy-3-C-hydroxymethyl-D-arabitol (3), and their 2,6-diaminopurine analogues 4 and 5 were synthesized from corresponding 1,4-anhydro-D-ribitol derivatives, which were readily obtained from D-glucose. The corresponding guanine isonucleosides 6 and 7 were obtained from 4 and 5 by enzymatic deamination with adenosine deaminase. Pyrimidine counterparts 8 and 9 were synthesized via construction of the pyrimidine moiety from amino derivatives of the 1,4-anhydro-D-arabitol derivatives. Antiviral activity of these ring-expanded derivatives of oxetanocins towards HSV-1, HSV-2, HCMV, and HBV in vitro was examined along with their cytotoxicity against L1210 and KB cells in vitro.

  (2R)-2-C-(Adenin-9-yl)-1,4-anhydro-2-deoxy-D-arabitol (2) 以及 (2R, 3R)-2-C-(adenin-9-yl)-1,4-anhydro-2,3-dideoxy-3-C-hydroxymethyl-D-arabitol (3) 与其对应的 2,6-diaminopurine 类似物 4 和 5，均通过相应 1,4-anhydro-D-ribitol 衍生物合成，这些衍生物可由 D-glucose 方便获得。通过腺苷脱氨酶催化去氨基反应，将化合物 4 和 5 转化为相应的鸟嘌呤异核苷 6 和 7。嘧啶类似物 8 和 9 则通过构建嘧啶基团，从 1,4-anhydro-D-arabitol 衍生物的氨基衍生物合成。在体外实验中，针对这些扩环的 oxetanocins 衍生物（包括 HSV-1、HSV-2、HCMV 和 HBV）的抗病毒活性进行了评估，同时测量了其对 L1210 和 KB 细胞的细胞毒性。
• 3'3' CYCLIC DINUCLEOTIDES CONTAINING ISONUCLEOTIDIC UNITS
  申请人：Institute of Organic Chemistry and Biochemistry AS CR, V.V.I.

  公开号：EP4056579A1

  公开（公告）日：2022-09-14

  The present disclosure relates to 3'3' cyclic dinucleotides containing isonucleotidic units, their pharmaceutically acceptable salts, their pharmaceutical composition and combinations of said substances and other medicaments or pharmaceuticals. The 3'3' cyclic dinucleotides have the following formula (J). The disclosure also relates to the use of said compounds for the treatment or prevention of diseases or conditions modifiable by STING protein modulation, such as cancer or viral, allergic and inflammatory diseases. In addition, these substances can be used as adjuvants in vaccines.

  本公开涉及含有异核苷酸单元的3'3'环状二核苷酸，及其药学上可接受的盐、其药物组合物以及上述物质与其他药物或药剂的组合。3'3'环状二核苷酸具有下述式(J)。 本公开还涉及所述化合物在治疗或预防可通过STING蛋白调节改善的疾病或病症中的用途，例如癌症或病毒性、过敏性和炎症性疾病。此外，这些物质可以用作疫苗的佐剂。
• Recognition and Inhibition of HIV Integrase by Novel Dinucleotides
  作者：Michael Taktakishvili、Nouri Neamati、Yves Pommier、Suresh Pal、Vasu Nair

  DOI：10.1021/ja992528d

  日期：2000.6.1

  HIV integrase is involved in the integration of viral DNA into chromosomal DNA, a biological process that occurs by a sequence involving HIV DNA splicing and subsequent integration steps. in the quest for small nucleotide systems with nuclease stability of the internucleotide phosphate bond and critical structural features for recognition and inhibition of HIV-1 integrase, we have discovered novel, nuclease-resistant dinucleotides with defined base sequences that are inhibitors of this key viral enzyme. Synthetic methodologies utilized for the syntheses of the novel dinucleotides include an excellent new phosphorylating agent.
• Synthesis and Antiviral Studies of Unsaturated Analogues of Isomeric Dideoxynucleosides
  作者：Sanjib Bera、Travis Mickle、Vasu Nair

  DOI：10.1080/07328319908044614

  日期：1999.11

  Novel isomeric dideoxynucleosides with unsaturation in the carbohydrate moiety have been synthesized. For example, isod4A was synthesized through a rearrangement reaction involving a cyclonucleoside. Support for the structures of both purine and pyrimidine d4 compounds came from UV, NMR, HRMS and single crystal Xray data. Interestingly, the single crystal X-ray data for isod4C shows that the base is almost orthogonal to the carbon-carbon double bond of the sugar moiety. Consistent with this is the observation that the UV data of this compound does not show a bathochromic shift compared to the saturated compound implying that the pi-bond is not in conjugation with the pyrimidine base.
• Resistance towards exonucleases of dinucleotides with stereochemically altered internucleotide phosphate bonds
  作者：Vasu Nair、Suresh Pal

  DOI：10.1016/j.bmcl.2003.07.034

  日期：2004.1

  Kinetic constants for the hydrolytic susceptibility of the internucleotide phosphate bond in normal dinucleotides [e.g., 2'-deoxycytidylyl-(3' > 5')-2'-deoxyuridine (dCpdU) and 2'-deoxyadenylyl-(3'--> 5')-2-deoxycytidine (dApdC)] and isomeric dinucleotides [e.g., 2-deoxycytidylyl-(3' --> 5')-1'-deoxy-2-isouridine (dCpisodU) and 1'-deoxy-2'-isoadenylyl-(3' --> 5')-2-deoxycytidine (isodApdC)], toward 5'- and 3'-exonucleases, phosphodiesterase I (PDE I) and phosphodiesterase II (PDE II) were experimentally determined and remarkable differences emerged. The study is of importance in the discovery of nuclease-stable inhibitors of HIV integrase, but may also have ramifications in the area of anti-sense oligonucleotides of therapeutic interest. (C) 2003 Elsevier Ltd. All rights reserved.