1-((2R,4S,5S)-4-azido-5-(((tert-butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione | 116195-69-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-((2R,4S,5S)-4-azido-5-(((tert-butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 3'-azido-5'-O-tert-butyldiphenylsilyl-3'-deoxythymidine；3'-azido-5'-O-(t-butyldiphenylsilyl)-3'-deoxythymidine；1-[(2R,4S,5S)-4-azido-5-[[tert-butyl(diphenyl)silyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 116195-69-8
• 化学式: C₂₆H₃₁N₅O₄Si
• 分子量: 505.649
• InChiKey: BKXJZJWTYLOFGK-YTFSRNRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-((2R,4S,5S)-4-azido-5-(((tert-butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione 在 吡啶 、 水 、 potassium carbonate 、 氯化铵 、 锌 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 100.0h， 生成 1-[2-[(7-chloroquinolin-4-yl)amino]ethyl]-3-[(2S,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]urea
  参考文献：
  名称：

  潜在的艾滋病毒/艾滋病-疟疾联合疗法的混合药物的合成和评估

  摘要：

  疟疾和艾滋病毒是我们这个时代最重要的全球性健康问题，每年共造成约300万人死亡。这两种疾病在世界许多地区（包括撒哈拉以南非洲，东南亚和南美）重叠，导致更高的合并感染风险。在这项研究中，我们生成并表征了同时靶向恶性疟原虫和HIV的杂合分子，以进行潜在的HIV /疟疾联合治疗。杂合分子是通过叠氮胸苷（AZT）与二氢青蒿素（DHA），四恶烷或4-氨基喹啉衍生物的共价融合而合成的。并对该小型文库进行了抗病毒和抗疟疾活性测试。我们的数据表明化合物7是体外最有效的分子，具有与DHA相当的抗血浆活性（IC 50  = 26 nM，SI> 3000），对HIV具有中等活性（IC 50  = 2.9μM； SI> 35），对HeLa细胞无毒在测定中使用的浓度（CC 50  > 100μM）。药代动力学研究进一步表明，化合物7在代谢上不稳定，并通过O-脱烷基反应裂解。这些研究说明了当以20 mg / kg口服

  DOI：

  10.1016/j.bmc.2012.06.038
• 作为产物：
  描述：

  5'-O-tert-butyldiphenylsilylthymidine 在 sodium hydroxide 、 sodium azide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-((2R,4S,5S)-4-azido-5-(((tert-butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Novel Fluorinated 2′,3′‐Dideoxynucleosides

  摘要：

  A series of 5-(trifluoroethoxymethyl)-2',3'-dideoxyuridines and 5-[bis(trifluorroethoxy)-methyl]-2', 3'-dideoxyuri dines have been prepared and screened for antiviral activity. The conformations of these compounds are discussed on the bases of NOE studies and the MO calculations. Modelling and NOE studies suggest both syn- and anti conformations for these 5-(2,2,2-trifluoroethoxymethyl)- and 5-[bis(2,2,2-trifluoroethoxy)-methyl]- derivatives. The NOE parameters are also suggested to be more attributable to the nature of the fluorine atom than to structural or conformational changes. Compounds 17, 26 and 30 showed some activity in anti-HIV-1 and anti-HIV-2 assays, but the compounds were devoid of activity against HSV and human rhinovirus. The compounds tested exhibited low cytotoxicity and were inactive against a bank of cancer cells in vitro.

  DOI：

  10.1081/ncn-120027814

文献信息

• Catalytic Staudinger—Vilarrasa Reaction for the Direct Ligation of Carboxylic Acids and Azides
  作者：Jordi Burés、Manuel Martín、Fèlix Urpí、Jaume Vilarrasa

  DOI：10.1021/jo802825e

  日期：2009.3.6

  2,2′-Dipyridyl diselenide (PySeSePy) is the catalyst or activator of choice for the direct reaction of carboxylic acids with azides and trimethylphosphine at room temperature. The mechanism of the process, which is not an aza-Wittig reaction, has been elucidated.

  2,2'-联吡啶二硒化物（PySeSePy）是室温下羧酸与叠氮化物和三甲基膦直接反应的选择催化剂或活化剂。已经阐明了该过程的机理，它不是aza-Wittig反应。
• Some novel nucleoside rearrangements effected by (diethylamino)sulphur trifluoride: synthesis and antiviral properties of some fluorine-containing 3′-azido-3′-deoxythymidine derivatives
  作者：Anne E. Lloyd、Paul L. Coe、Richard T. Walker、Oliver W. Howarth

  DOI：10.1016/s0022-1139(00)80089-5

  日期：1993.6

  The reaction of pyrimidine nucleoside 5′-aldehydes with (diethylamino)sulphur trifluoride(DAST) to produce 5′-deoxy-5′,5′-difluoronucleosides is reported. The preferred reactionis the production of the O2,5′-anhydro-5′-fluoronucleoside. If this is prevented by substitutionat 04 or N-3 then, in the former case, either DAST no longer reacts or underdrastic conditions the C(1′)N(1) bond breaks and the

  报道了嘧啶核苷5'-醛与（二乙基氨基）三氟化硫（DAST）反应生成5'-脱氧-5'，5'-二氟核苷。优选reactionis生产的O 2，5'-脱水-5'-氟核苷。如果通过在0 4或N-3处取代来防止这种情况，那么在前一种情况下，DAST不再反应或在剧烈条件下C（1'）N（1）键断裂，杂环碱基仍被C-5'连接→O 2糖基氟化物。在后一种情况下，2'，3'-O-异丙基亚氨基尿苷的5'-醛为5'-脱氧-5'，5'-二氟化合物作为唯一可识别的产物。以AZT的5'-醛（在N-3处适当保护）为起始原料，用DAST处理可生成糖基氟和其5'-脱氧-5'，5'-二氟AZT衍生物的非对映异构体混合物，其中3'可以分离出-叠氮基-3'，5'-二脱氧氧基-5'，5'-二氟胸苷。该化合物无毒，对高达100μM的1型人类免疫缺陷病毒（HIV-1）也没有任何活性。
• AZT-prolinamide: the nucleoside derived pyrrolidine catalysts for asymmetric aldol reactions using water as solvent
  作者：Tumma Naresh、Togapur Pavan Kumar、Kothapalli Haribabu、Srivari Chandrasekhar

  DOI：10.1016/j.tetasy.2014.08.007

  日期：2014.10

  New pyrrolidine catalysts based on a nucleoside and proline, AZT-prolinamides, were synthesized and successfully employed for the enantioselective direct aldol reaction of aldehydes with ketones. These catalysts proved to be effective in promoting the reaction, in additive free water media with 15 mol % loading. The products, beta-hydroxy carbonyl compounds were obtained in high yields and stereoselectivities. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of hybrid drugs for a potential HIV/AIDS-malaria combination therapy
  作者：Makoah N. Aminake、Aman Mahajan、Vipan Kumar、Renate Hans、Lubbe Wiesner、Dale Taylor、Carmen de Kock、Anne Grobler、Peter J. Smith、Marc Kirschner、Axel Rethwilm、Gabriele Pradel、Kelly Chibale

  DOI：10.1016/j.bmc.2012.06.038

  日期：2012.9

  sub-Saharan Africa, Southeast Asia and South America, leading to a higher risk of co-infection. In this study, we generated and characterized hybrid molecules to target Plasmodium falciparum and HIV simultaneously for a potential HIV/malaria combination therapy. Hybrid molecules were synthesized by the covalent fusion of azidothymidine (AZT) with dihydroartemisinin (DHA), a tetraoxane or a 4-aminoquinoline

  疟疾和艾滋病毒是我们这个时代最重要的全球性健康问题，每年共造成约300万人死亡。这两种疾病在世界许多地区（包括撒哈拉以南非洲，东南亚和南美）重叠，导致更高的合并感染风险。在这项研究中，我们生成并表征了同时靶向恶性疟原虫和HIV的杂合分子，以进行潜在的HIV /疟疾联合治疗。杂合分子是通过叠氮胸苷（AZT）与二氢青蒿素（DHA），四恶烷或4-氨基喹啉衍生物的共价融合而合成的。并对该小型文库进行了抗病毒和抗疟疾活性测试。我们的数据表明化合物7是体外最有效的分子，具有与DHA相当的抗血浆活性（IC 50  = 26 nM，SI> 3000），对HIV具有中等活性（IC 50  = 2.9μM； SI> 35），对HeLa细胞无毒在测定中使用的浓度（CC 50  > 100μM）。药代动力学研究进一步表明，化合物7在代谢上不稳定，并通过O-脱烷基反应裂解。这些研究说明了当以20 mg / kg口服
• Synthesis and Antiviral Activity of Novel Fluorinated 2′,3′‐Dideoxynucleosides
  作者：Piyush Kumar、Kazue Ohkura、Jan Balzarini、Erik De Clercq、Koh‐ichi Seki、Leonard I. Wiebe

  DOI：10.1081/ncn-120027814

  日期：2004.1.1

  A series of 5-(trifluoroethoxymethyl)-2',3'-dideoxyuridines and 5-[bis(trifluorroethoxy)-methyl]-2', 3'-dideoxyuri dines have been prepared and screened for antiviral activity. The conformations of these compounds are discussed on the bases of NOE studies and the MO calculations. Modelling and NOE studies suggest both syn- and anti conformations for these 5-(2,2,2-trifluoroethoxymethyl)- and 5-[bis(2,2,2-trifluoroethoxy)-methyl]- derivatives. The NOE parameters are also suggested to be more attributable to the nature of the fluorine atom than to structural or conformational changes. Compounds 17, 26 and 30 showed some activity in anti-HIV-1 and anti-HIV-2 assays, but the compounds were devoid of activity against HSV and human rhinovirus. The compounds tested exhibited low cytotoxicity and were inactive against a bank of cancer cells in vitro.