[(2S,5R)-5-(6-氧代-3,6-二氢-9H-嘌呤-9-基)四氢-2-呋喃基]甲基乙酸酯 | 130676-58-3

• 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: [(2S,5R)-5-(6-氧代-3,6-二氢-9H-嘌呤-9-基)四氢-2-呋喃基]甲基乙酸酯
• 英文名称: 5'-O-acetyl-2',3'-dideoxyinosine
• 英文别名: [(2S,5R)-5-(6-oxo-3H-purin-9-yl)oxolan-2-yl]methyl acetate；[(2S,5R)-5-(6-oxo-1H-purin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 130676-58-3
• 化学式: C₁₂H₁₄N₄O₄
• 分子量: 278.268
• InChiKey: MVUMVNRFAFXMSZ-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(2S,5R)-5-(6-氧代-3,6-二氢-9H-嘌呤-9-基)四氢-2-呋喃基]甲基乙酸酯 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 氯仿 为溶剂， 反应 8.0h， 以9%的产率得到
  参考文献：
  名称：

  Synthesis and¹H and¹³C NMR Spectral Characteristics of 8-Bromo-2′,3′-Dideoxyguanosine and 8-Bromo-2′,3′-Dideoxyinosine¹

  摘要：

  Reaction of 2',3'-dideoxyguanosine 1a as 5'-O-tert-butyldimethylsilyl derivative Ib and 2',3'-dideoxyinosine 2a with bromine in acetate buffer conducted in heterogeneous medium afforded 8-bromo-2',3'-dideoxyguanosine 3a (44% after deprotection) and 8-bromo-2',3'-dideoxyinosine 4a (12%) respectively. The change of conformational preferences anti --> syn on 8-bromo substitution of 2',3'-dideoxynucleosides is reflected in the H-1 and C-13 NMR spectra by characteristic shifts of H-2', H-3', C-2' and C-3' signals.

  DOI：

  10.1080/07328319608002035
• 作为产物：
  描述：

  Imidazole-1-carbothioic acid O-[(2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(6-oxo-1,6-dihydro-purin-9-yl)-tetrahydro-furan-3-yl] ester 在 偶氮二异丁腈 、 三正丁基氢锡 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 吡啶 为溶剂， 反应 2.5h， 生成 [(2S,5R)-5-(6-氧代-3,6-二氢-9H-嘌呤-9-基)四氢-2-呋喃基]甲基乙酸酯
  参考文献：
  名称：

  Synthesis and¹H and¹³C NMR Spectral Characteristics of 8-Bromo-2′,3′-Dideoxyguanosine and 8-Bromo-2′,3′-Dideoxyinosine¹

  摘要：

  Reaction of 2',3'-dideoxyguanosine 1a as 5'-O-tert-butyldimethylsilyl derivative Ib and 2',3'-dideoxyinosine 2a with bromine in acetate buffer conducted in heterogeneous medium afforded 8-bromo-2',3'-dideoxyguanosine 3a (44% after deprotection) and 8-bromo-2',3'-dideoxyinosine 4a (12%) respectively. The change of conformational preferences anti --> syn on 8-bromo substitution of 2',3'-dideoxynucleosides is reflected in the H-1 and C-13 NMR spectra by characteristic shifts of H-2', H-3', C-2' and C-3' signals.

  DOI：

  10.1080/07328319608002035

文献信息

• Prodrugs of 2',3'-Dideoxyinosine(DDI): Improved Oral Bioavailability via Hydrophobic Esters.
  作者：Takeo KAWAGUCHI、Tetsuya HASEGAWA、Toshinobu SEKI、Kazuhiko JUNI、Yasunori MORIMOTO、Akira MIYAKAWA、Mineo SANEYOSHI

  DOI：10.1248/cpb.40.1338

  日期：——

  Five ester prodrugs of 2'3'-dideoxyinosine (DDI) were synthesized for the purpose of improving oral bioavailability. The prodrugs, acetate (C2-DDI), octanoate (C8-DDI), stearate (C18-DDI), benzoate (Bz-DDI), and hemisuccinate (Suc-DDI) were proved to quantitatively regenerate their parent drug by enzymatic hydrolysis. Though the chemical stability of the prodrugs under acidic conditions was not improved, their solubility in water was significantly decreased by esterification, except for Suc-DDI. Bioavailability was evaluated by oral administration to rats. Two hydrophobic prodrugs (C8-DDI and Bz-DDI) showed higher absolute bioavailability (23.5% and 31.0%, respectively) than did DDI (15.2%), though that of C2-DDI (11.5%) and Suc-DDI (4.5%) was poor.

  为了提高口服生物利用度，我们合成了五种 2'3'-dideoxyinosine (DDI) 的酯类原药。经证明，醋酸酯（C2-DDI）、辛酸酯（C8-DDI）、硬脂酸酯（C18-DDI）、苯甲酸酯（Bz-DDI）和半琥珀酸酯（Suc-DDI）原药在酶水解作用下可定量生成母药。虽然这些原药在酸性条件下的化学稳定性没有得到改善，但除 Suc-DDI 外，它们在水中的溶解度因酯化作用而显著降低。通过给大鼠口服评估了生物利用度。两种疏水性原药（C8-DDI 和 Bz-DDI）的绝对生物利用度（分别为 23.5% 和 31.0%）高于 DDI（15.2%），但 C2-DDI （11.5%）和 Suc-DDI （4.5%）的生物利用度较低。
• PROCESS FOR PRODUCING 2',3'-DIDEOXY-2',3'-DIDEHYDRONUCLEOSIDE
  申请人：YUKI GOSEI KOGYO CO., LTD.

  公开号：EP0493602A1

  公开（公告）日：1992-07-08

  A process for producing 2',3'-dideoxy-2',3'-didehydronucleoside useful as the starting material of medicines readily at a low cost, which comprises the step (a) of reacting a ribonucleoside derivative of general formula (II) with an acid anhydride in the presence of a catalyst to obtain an intermediate of general formula (III) and the step (b) of decarboxylating the intermediate (III) under a neutral or basic condition to obtain 2',3'-dideoxy-2',3'-didehydronucleoside of general formula (I), wherein R¹ represents optionally protected hydroxy; R² and R³ represent each optionally substituted alkyl or phenyl; and B represents a purine or pyrimidine nucleic acid base.

  一种以低成本生产可用作药物起始原料的 2',3'-二脱氧-2',3'-二脱氢核苷的工艺、该工艺包括步骤(a) 在催化剂存在下，使通式(II)的核糖核苷衍生物与酸酐反应，得到通式(III)的中间体；步骤(b) 在中性或碱性条件下，使中间体(III)脱羧，得到通式(I)的 2',3'-二脱氧-2',3'-二脱氢核苷，其中 R¹ 代表任选受保护的羟基；R² 和 R³ 分别代表任选取代的烷基或苯基；以及 B 代表嘌呤或嘧啶核酸碱基。
• Synthesis of haptens for the development of immunoassays for the monitoring of intracellular anti-HIV nucleosides and nucleotides
  作者：Thierry Brossette、Emmanuel Klein、Christophe Créminon、Jacques Grassi、Charles Mioskowski、Luc Lebeau

  DOI：10.1016/s0040-4020(01)00800-6

  日期：2001.9

  A series of nine modified dideoxynucleosides and dideoxynucleotides has been synthesized for preparing antigenic conjugates with keyhole lympet haemocyanin in order to produce specific antibodies, and develop immunoassays. Derivatives of ddI, ddA, d4T, 3TC, and the corresponding 5 ' -O-monophosphates were designed incorporating an amino spacer at the base for conjugation with the proteinic antigenic carrier. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Lipase-catalyzed protection of the hydroxy groups of the nucleosides inosine and 2′-deoxyinosine: A new chemoenzymatic synthesis of the antiviral drug 2′,3′-dideoxyinosine
  作者：Pierangela Ciuffreda、Silvana Casati、Enzo Santaniello

  DOI：10.1016/s0960-894x(99)00228-0

  日期：1999.6

  The selective acylation of the hydroxy groups of the nucleosides inosine la and 2'-deoxyinosine Ib has been achieved in the presence of Candida antarctica and Pseudomonas sp. lipases in organic solvents; starting from the 5'-acetyl derivative of 2'-deoxyinosine, compound 5a, an efficient chemoenzymatic synthesis of the antiviral drug 2',3'-dideoxyinosine 1c has been achieved, (C) 1999 Elsevier Science Ltd. All rights reserved.
• AMINO, YUSUKEH;IVAGAMI, XISAO
  作者：AMINO, YUSUKEH、IVAGAMI, XISAO

  DOI：——

  日期：——