2,2''-anhydro-1-(3'',5''-di-O-acetyl-β-D-arabinofuranosyl)uracil | 28309-53-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2,2''-anhydro-1-(3'',5''-di-O-acetyl-β-D-arabinofuranosyl)uracil
• 英文别名: 2,2'-Anhydro-1-(3,5-di-O-acetyl-β-D-arabinofuranosyl)uracil；2,2'-anhydro-1-(3,5-diacetoxy-β-D-arabinofuranosyl)uracil；3',5'-di-O-acetyl-O²,2'-cyclouridine；3',5'-Di-O-acetyl-2,2'-anhydrouridine；2,2'-O-cyclouridine diacetate；(3aS)-3c-acetoxy-2t-acetoxymethyl-(3ar,9ac)-2,3,3a,9a-tetrahydro-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-6-one；3',5'-diacetyl-O^2^,2-cyclouridine；[(2R,4R,5R,6S)-5-acetyloxy-10-oxo-3,7-dioxa-1,9-diazatricyclo[6.4.0.02,6]dodeca-8,11-dien-4-yl]methyl acetate
• CAS: 28309-53-7
• 化学式: C₁₃H₁₄N₂O₇
• 分子量: 310.263
• InChiKey: AXUJTCUYAOPZNY-KXGXSXBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,2''-anhydro-1-(3'',5''-di-O-acetyl-β-D-arabinofuranosyl)uracil 在 Rh on carbon 硫化氢 、 氢气 、 sodium methylate 作用下， 以 吡啶 、 甲醇 为溶剂， 25.0 ℃ 、360.0 kPa 条件下， 反应 170.0h， 生成 1-(5-O-acetyl-2-deoxy-2-mercapto-β-D-arabinofuranosyl)-2-O-methyl-5,6-dihydrouracil
  参考文献：
  名称：

  Skaric, Vinko; Matulic-Adamic, Jasenka, Journal of the Chemical Society. Perkin transactions I, 1985, p. 779 - 784

  摘要：

  DOI：
• 作为产物：
  描述：

  2,5'-脱水尿苷 在 4-二甲氨基吡啶 、 二正丁基氧化锡 、 三乙胺 作用下， 以 六甲基磷酰三胺 、 二氯甲烷 为溶剂， 生成 2,2''-anhydro-1-(3'',5''-di-O-acetyl-β-D-arabinofuranosyl)uracil
  参考文献：
  名称：

  Nucleosides. CXLIII. Synthesis of 5'-deoxy-5'-substituted-2,2'-anhydro-1-(.BETA.-D-arabinofuranosyl)uracils. A new 2,5'- to 2,2'-anhydro-nucleoside transformation. Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides.

  摘要：

  使用NaOAc、NaN3、LiCl或LiBr等亲核试剂处理2,5'-脱水-3'-O-乙酰-2'-O-三氟甲磺酰尿苷，并未得到2'-取代的2,5'-脱水阿糖呋喃尿嘧啶，而是生成了2,2'-脱水-1-(5-取代-β-D-阿糖呋喃糖基)尿嘧啶。

  DOI：

  10.1248/cpb.35.4494

文献信息

• New Telluride-Mediated Elimination for Novel Synthesis of 2′,3′-Didehydro-2′,3′-dideoxynucleosides
  作者：Jia Sheng、Abdalla E. A. Hassan、Zhen Huang

  DOI：10.1021/jo7025806

  日期：2008.5.1

  Several 2′,3′-dideoxynucleosides (ddNs) and 2′,3′-didehydro-2′,3′-dideoxynucleosides (d4Ns) are FDA-approved anti-HIV drugs. Via conveniently synthesized 2,2′-anhydronucleosides, we have developed a novel synthesis of d4Ns by discovering and applying a new telluride-mediated elimination reaction. Our experiment results show that after substitution of 2,2′-anhydronucleosides with a telluride monoanion

  几种2'，3'-双脱氧核苷（ddNs）和2'，3'-双脱氢-2'，3'-双脱氧核苷（d4Ns）是FDA批准的抗HIV药物。通过方便地合成的2,2'-脱水核苷，我们通过发现和应用新的碲化物介导的消除反应，开发了一种新颖的d4Ns合成方法。我们的实验结果表明，在将2,2'-脱水核苷替换为碲化物单阴离子后，形成了碲化物中间体，其消除导致形成烯烃产物（d4Ns）。我们的机理研究表明，碲化物辅助反应包括两个步骤：取代（或添加）和消除。通过使用二甲基二碲化物（0.1当量）作为试剂，通过碲化物介导的消除反应，可以合成d4Ns，产率高达90％。
• Nucleosides and nucleotides. XII. Synthesis and properties of 2'-deoxy-2'-mercaptouridine and its derivatives.
  作者：MASAOKI IMAZAWA、TOHRU UEDA、TYUNOSIN UKITA

  DOI：10.1248/cpb.23.604

  日期：——

  New thiosugar nucleosides, 2'-deoxy-2'-mercaptouridine (III), its disulfide (IV), 2'-deoxy-2'-mercapto-3', 5'-di-O-acetyluridine (V), and 2'-deoxy-2'-methyl-thiouridine (VI) have been synthesized. The present synthetic method involves the use of 2'-deoxy-2'-acetylthio-3', 5'-di-O-acetyluridine (II) as the intermediate which was obtained by the reaction of 2, 2'-cyclo-3', 5'-di-O-acetyluridine (I) with thioacetic acid. The proton magnetic resonance (PMR) data of these compounds suggested that the introduction of sulfuratom at 2'-position resulted in the furanose ring puckering that is extremely biased to C2' endo-mode. 2'-Deoxy-2', 6-epithio-5, 6-dihydro-arabinofuranosyluracil (VIIIb), the 2'-epimer of III in an 2', 6-epithio form, was also synthesized.

  新型硫糖核苷，包括2'-脱氧-2'-巯基尿苷 (III)、其二硫化物 (IV)、2'-脱氧-2'-巯基-3',5'-二-O-乙酰尿苷 (V) 和2'-脱氧-2'-甲基硫尿苷 (VI) 已被合成。当前的合成方法使用2'-脱氧-2'-乙酰硫-3',5'-二-O-乙酰尿苷 (II) 作为中间体，后者是通过2,2'-环式-3',5'-二-O-乙酰尿苷 (I) 与硫代乙酸反应获得的。这些化合物的质子核磁共振 (PMR) 数据表明，在2'位引入硫原子导致呋喃环呈现明显偏向C2'内向的扭曲。此外，2'-脱氧-2',6-硫醇-5,6-二氢阿拉伯呋喃糖基尿嘧啶 (VIIIb)，也是III的2'-表异构体，在2',6-硫醇形式下合成。
• Solid-Phase Microextraction in the Determination of Methadone in Human Saliva by Gas Chromatography-Mass Spectrometry
  作者：A. C. dos Santos Lucas、A. Bermejo、P. Fernandez、M. J. Tabernero

  DOI：10.1093/jat/24.2.93

  日期：2000.3.1

  Solid-phase microextraction (SPME) with a 100-µm polydimethylsiloxane film fiber was applied to the determination of methadone and 2-ethylidine-3,3-diphenylpyrrolidine (EDDP) by GC-MS in human saliva and compared with liquid-liquid extraction. A shorter extraction time of 30 min with the fiber was obtained, speeding up the total analysis time. Linearity was found for SPME from 0.05 to 2.0 µg/mL (r = 0.9976 for methadone; r = 0.9988 for EDDP) with precision between 0.7 and 4.3% for saliva spiked with 0.2 and 1.5 µg/mL of methadone and EDDP. The limit of detection using SPME was 0.04 Ég/mL for methadone and 0.008 µg/mL for EDDP. Analytical recoveries of SPME and liquid-liquid extraction ranged from 98.8 to 103.6%. The use of deuterated internal standard by both methods have yielded comparable results. Thus, the SPME method is highly accurate, precise, and useful for determination of methadone and EDDP in saliva.

  固相微萃取（SPME）采用100微米聚二甲基硅氧烷薄膜纤维用于人类唾液中美沙酮和2-乙基氢化-3,3-二苯基吡咯烷（EDDP）的GC-MS测定，并与液-液萃取进行了比较。使用纤维的萃取时间缩短至30分钟，加快了总分析时间。SPME的线性范围为0.05至2.0 µg/mL（美沙酮的r = 0.9976；EDDP的r = 0.9988），对于添加0.2和1.5 µg/mL美沙酮和EDDP的唾液，其精密度在0.7%到4.3%之间。使用SPME时，美沙酮的检测限为0.04 µg/mL，EDDP的检测限为0.008 µg/mL。SPME和液-液萃取的分析回收率范围为98.8%到103.6%。两种方法使用氘代内标均获得了可比结果。因此，SPME方法在美沙酮和EDDP的唾液测定中具有很高的准确性、精密度和实用性。
• 2,2′-Anhydro-1-(3′,5′-di-<i>O</i>-acetyl-β-<scp>D</scp>-arabinofuranosyl)uracil, a cyclouridine nucleoside with a C4′-<i>endo</i>furanosyl conformation
  作者：Ying Fu、Yin-Xia He、Hong-Xia Hou、Wen-Bo Zhu、Hu-Lin Li、Chao Wu、Fang-Yan Xian

  DOI：10.1107/s0108270113000395

  日期：2013.3.15

  2,2′-Anhydro-1-(3′,5′-di-O-acetyl-β-D-arabinofuranosyl)uracil, C₁₃H₁₄N₂O₇, was obtained by refluxing 2′,3′-O-(methoxymethylene)uridine in acetic anhydride. The structure exhibits a nearly perfect C4′-endo(⁴E) conformation. The best four-atom plane of the five-membered furanose ring is O—C—C—C, involving the C atoms of the fused five-membered oxazolidine ring, and the torsion angle is only −0.4 (2)°. The oxazolidine ring is essentially coplanar with the six-membered uracil ring [r.m.s. deviation = 0.012 (5) Å and dihedral angle = −3.2 (3)°]. The conformation at the exocyclic C—C bond isgauche–transwhich is stabilized by various C—H...π and C—O...π interactions.

  将 2′,3′-O-(甲氧基亚甲基)尿苷在乙酸酐中回流得到 2,2′-脱水-1-(3′,5′-二-O-乙酰基-β-D-阿拉伯呋喃糖基)尿苷，C13H14N2O7。该结构呈现出近乎完美的 C4′-内多（4E）构象。五元呋喃糖环的最佳四原子平面为 O-C-C-C-C，涉及融合的五元恶唑烷环的 C 原子，扭转角仅为 -0.4 (2)°。恶唑烷环与六元尿嘧啶环基本共面[r.m.s. 偏差 = 0.012 (5) Å，二面角 = -3.2 (3)°]。外环 C-C 键的构象为高切反式，通过各种 C-H...π 和 C-O...π 相互作用而稳定。
• Studies on biologically active nucleosides and nucleotides. 2. A convenient one-step synthesis of 2,2'-anhydro-1-(3',5'-di-O-acyl-.beta.-D-arabinofuranosyl)pyrimidines from pyrimidine ribonucleosides
  作者：Kazuhiko Kondo、Ichizo Inoue

  DOI：10.1021/jo00437a003

  日期：1977.8