5'-O-benzoyl-2',3'-didehydro-2',3'-dideoxyuridine | 6038-56-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 5'-O-benzoyl-2',3'-didehydro-2',3'-dideoxyuridine
• 英文别名: [(2S,5R)-5-(2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methyl benzoate
• CAS: 6038-56-8
• 化学式: C₁₆H₁₄N₂O₅
• 分子量: 314.298
• InChiKey: ICKLGKYSKWIOSR-GXTWGEPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5'-O-benzoyl-2',3'-didehydro-2',3'-dideoxyuridine 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 2’,3’-二脱氢-2’,3’-二脱氧尿苷
  参考文献：
  名称：

  新的碲化物介导的消除反应，可合成2'，3'-Didehydro-2'，3'-Dideoxynucleosides

  摘要：

  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％。

  DOI：

  10.1021/jo7025806
• 作为产物：
  描述：

  [(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2-sulfanylidene-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl benzoate 生成 5'-O-benzoyl-2',3'-didehydro-2',3'-dideoxyuridine
  参考文献：
  名称：

  DUDYCZ, L. W., NUCLEOSIDES AND NUCLEOTIDES , 8,(1989) N, C. 35-41

  摘要：

  DOI：

文献信息

• [d4U]-Spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase
  作者：Yassir Younis、Roger Hunter、Clare I. Muhanji、Ian Hale、Rajinder Singh、Christopher M. Bailey、Todd J. Sullivan、Karen S. Anderson

  DOI：10.1016/j.bmc.2010.05.025

  日期：2010.7

  propargyl-4-PEG (15d) have been synthesized and biologically evaluated as RT inhibitors against HIV-1. The key step in their synthesis involved a Sonogashira coupling of 5-iodo d4U’s benzoate with an alkynylated tethered HI-236 precursor followed by introduction of the HI-236 thiourea functionality. Biological evaluation in both cell-culture (MT-2 cells) as well as using an in vitro RT assay revealed 15a–c to

  [d4U]-间隔基-[HI-236] 类型的四种双药 HIV NRTI/NNRTI 抑制剂15a – d，其中间隔基变化为 1-丁炔基 ( 15a )、炔丙基-1-PEG ( 15b )、炔丙基-2-PEG ( 15c ) 和炔丙基-4-PEG ( 15d ) 已被合成并作为抗 HIV-1 的 RT 抑制剂进行生物学评估。他们合成的关键步骤涉及 5-碘 d4U 苯甲酸酯与炔基化 HI-236 前体的 Sonogashira 偶联，然后引入 HI-236 硫脲官能团。细胞培养（MT-2 细胞）以及使用体外 RT 测定的生物学评估显示15a – c比 d4T 更活跃。然而，总体而言，结果表明衍生物作为链延长的 NNRTIs，其中对于15b - d，核苷组分可能位于口袋外，但没有证据表明 NRTI 和 NNRTI 位点之间存在任何协同双结合。这部分归因于由于激酶识别失败导致双药核苷组分缺乏磷酸化，而结合
• Synthesis and in vitro evaluation of some modified 4-thiopyrimidine nucleosides for prevention or reversal of AIDS - associated neurological disorders
  作者：Eduardo Palomino、Bernard R. Meltsner、David Kessel、Jerome P. Horwitz

  DOI：10.1021/jm00163a043

  日期：1990.1

  developed for the initial synthesis of AZT. Thiation of 2',3'-didehydro-3'-deoxythymidine (4a) and 2',3'-didehydro-2',3'-dideoxyuridine (4c) was carried out with Lawesson's reagent on the corresponding 5'-O-benzoate esters, 4b and 4d, to give 5a and 5c, respectively. The latter, on alkaline hydrolysis, gave 2',3'-didehydro-3'-deoxy-4-thiothymidine (5b) and 2',3'-didehydro-2',3'-dideoxyuridine (5d), respectively

  描述了几个修饰的嘧啶核苷（包括3'-叠氮基3'-脱氧胸苷（AZT））在C-4羰基上的氧-硫交换，目的是增强亲脂性，从而传递至中枢神经系统在不损害亲本结构的抗HIV活性的前提下制备出类似的硫磺类似物。从4-硫代胸苷（1）开始制备3'-叠氮基-3'-脱氧-4-硫代胸腺嘧啶（3），并采用了用于AZT初始合成的相同方法。用Lawesson试剂在相应的5'-O-上进行2'，3'-二氢-3'-脱氧胸苷（4a）和2'，3'-二氢-2'，3'-二脱氧尿苷（4c）的亚硫酰化。苯甲酸酯4b和4d分别得到5a和5c。后者经碱水解，得到2'，3'-二氢-3' -脱氧-4-硫代胸苷（5b）和2'，3'-二氢-2'，3'-二脱氧尿苷（5d）。将相同系列的反应应用于2'，3'-二脱氧尿苷（6a）和3'-脱氧胸苷（6b）的5'-O-苯甲酸酯，得到2'，3'-二脱氧-4-硫尿苷（7d ）和3'-脱氧-4-硫代胸苷（7b）。
• Prodrugs of 2',3'- Didehydro-2',3'-Dideoxynucleosides
  申请人：Bristol-Myers Squibb Company

  公开号：EP0340778A2

  公开（公告）日：1989-11-08

  There are disclosed novel prodrugs of 2′,3′-didehydro-2′,3′-dideoxynucleosides, for example, of 2′,3′-didehydro-2′,3′-dideoxythymidine. The prodrugs are hydrolyzable under physiological conditions to yield compound which are useful as antiviral agents, especially as agents effective against the human immunodeficiency viruses (HIV).

  公开了 2′,3′-二脱氢-2′,3′-二脱氧核苷的新型原药，例如 2′,3′-二脱氢-2′,3′-二脱氧胸苷。这些原药在生理条件下可水解，生成的化合物可用作抗病毒剂，尤其是对人类免疫缺陷病毒（HIV）有效的药物。
• Highly efficient synthesis of 2′,3′-didehydro-2′,3′-dideoxy-β-nucleosides through a sulfur-mediated reductive 2′,3′-trans-elimination. From iodomethylcyclopropanes to thiirane analogs
  作者：Luis Álvarez de Cienfuegos、Antonio J. Mota、Concepción Rodríguez、Rafael Robles

  DOI：10.1016/j.tetlet.2004.11.087

  日期：2005.1

  Taking into account the thiophilic properties of iodine, a very simple methodology to achieve 2,3'-didehydro-2'.3'-dideoxy-beta-nucleosides in high yield was performed, using mild, and inexpensive conditions. by means of the treatment of 2'-deoxy-3'.5'-dibenzoyl-2'-iodo-beta-nucleoside derivatives with NaHS. The process has shown to be highly dependent of the relative geometry between the iodine atom and the adjacent leaving group. In this way, different essays carried out with pyranose derivatives. have concluded in no reaction when the vicinal groups to eliminate do not adopt a trans-diaxial disposition. In addition, the treatment of 2-iodomethyl-cyclopropane-1,1-dicarboxylic acid diethyl ester under the same conditions softly and readily leads to the obtention of a mixture of the expected 2-allyl-malonic acid diethyl ester (as the minor product) and the thiirane derivative 2-thiiranytmethyl-malonic acid diethyl ester (as the major product). In this case, the responsible of the reaction progress are the nucleophilic properties of the sulfur atom rather than the thiophilic character of the iodine atom. (C) 2004 Elsevier Ltd. All rights reserved.
• [d4U]-butyne-[HI-236] as a non-cleavable, bifunctional NRTI/NNRTI HIV-1 reverse-transcriptase inhibitor
  作者：Roger Hunter、Clare I. Muhanji、Ian Hale、Christopher M. Bailey、Aravind Basavapathruni、Karen S. Anderson

  DOI：10.1016/j.bmcl.2007.01.107

  日期：2007.5

  The synthesis of bifunctional compound 10 consisting of d4U joined at C-5 to a butynyl spacer attached to HI-236 is reported using a Sonogashira coupling as a key step. As a non-cleavable bifunctional HIV inhibitor incorporating an NRTI with an NNRTI, 10 shows good inhibitory activity (EC50 = 250 nM) against HIV (IIIB) replication in NIT-2 cell culture, which is eight times greater than that of d4T and between those of the two component drugs. (c) 2007 Elsevier Ltd. All rights reserved.