1-(2,3-二脱氧-3-氟-5-O-三苯甲基呋喃戊糖基)-5-甲基-2,4(1H,3H)-嘧啶二酮 | 135197-63-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: 1-(2,3-二脱氧-3-氟-5-O-三苯甲基呋喃戊糖基)-5-甲基-2,4(1H,3H)-嘧啶二酮
• 英文名称: 3'-Fluoro-5'-O-trityl-deoxythymidine
• 英文别名: 3'-Deoxy-3'-fluoro-5'-O-tritylthymidine；1-[(2R,4S,5R)-4-fluoro-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 135197-63-6
• 化学式: C₂₉H₂₇FN₂O₄
• 分子量: 486.543
• InChiKey: GFDJOSNZNLVRCL-JIMJEQGWSA-N

物化性质

• 溶解度：
  溶于二氯甲烷、二甲基甲酰胺、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2,3-二脱氧-3-氟-5-O-三苯甲基呋喃戊糖基)-5-甲基-2,4(1H,3H)-嘧啶二酮 在 对甲苯磺酸 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 0.33h， 以64%的产率得到3’-脱氧-3-氟胸苷
  参考文献：
  名称：

  3'-氟-3'-脱氧胸腺嘧啶核苷的合成及其18 F-放射性标记的研究，作为无创性监测抗艾滋病药物生物分布的示踪剂

  摘要：

  3'-叠氮基胸苷（AZT）的氟化类似物3'-Fluoro-3'-脱氧胸苷（FDT）对HIV病毒更具活性，但比AZT毒性更大。由于它具有氟原子，因此可以用18 F标记，以监测该药物的生物分布和靶向性。已经开发出适用于18 F标记的FDT的新合成方法。在用三苯甲基保护5'-羟基后，将3'-羟基用Lyxo构型的甲磺酰基取代。用18 F氟化钾和Crown-18醚处理可得到18 F标记的氟代衍生物，在去三苯甲基化后可得到18 FF FDT具有7％的标记效率。这是首次报道使用氟化钾合成3'-氟-5'-O-三苯甲基脱氧胸苷并制备其18 F标记的类似物。在中间体化合物中掺入18 F并分离终产物所需的时间相当短（大约2小时），这将有足够的时间对这种短寿命的放射性核素进行生物学研究。

  DOI：

  10.1016/s0022-1139(00)82356-8
• 作为产物：
  描述：

  5’-三苯甲基-2’-脱氧-2,3’-双脱氢胸苷 在 氢氟酸 、 triisopropylaluminium 作用下， 以 乙二醇二甲醚 、 甲苯 为溶剂， 反应 4.0h， 以52%的产率得到1-(2,3-二脱氧-3-氟-5-O-三苯甲基呋喃戊糖基)-5-甲基-2,4(1H,3H)-嘧啶二酮
  参考文献：
  名称：

  Hydrofluorination of anhydrothymidine via soluble aluminum derivatives

  摘要：

  A new method to stereospecifically hydrofluorinate anhydrothymidine has been discovered which allows the product to be obtained in higher yields than the current literature method.

  DOI：

  10.1016/s0040-4039(00)71244-5

文献信息

• 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.
• Synthesis and evaluation of thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase
  作者：Veerle Vanheusden、Hélène Munier-Lehmann、Sylvie Pochet、Piet Herdewijn、Serge Van Calenbergh

  DOI：10.1016/s0960-894x(02)00551-6

  日期：2002.10

  A number of 2'- and 3'-modified thymidine 5'-O-monophosphate analogues were synthesized as potential leads for new anti-mycobacterial drugs. Evaluation of their affinity for Mycobacterium tuberculosis thymidine monophosphate kinase showed that a 2'-halogeno substituent and a 3'-azido function are the most favorable leads for further development of potent inhibitors of this enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.
• STERZYCKI, R.;MANSURI, M.;BRANKOVAN, V.;BUROKER, R.;GHAZZOULI, I.;HITCHCO+, NUCLEOSIDES AND NUCLEOTIDES, 8,(1989) N-6, C. 1115-1117
  作者：STERZYCKI, R.、MANSURI, M.、BRANKOVAN, V.、BUROKER, R.、GHAZZOULI, I.、HITCHCO+

  DOI：——

  日期：——
• Synthesis of 3′-fluoro-3′-deoxythymidine and studies of its 18F-radiolabeling, as a tracer for the noninvasive monitoring of the biodistribution of drugs against AIDS
  作者：I.K. Wilson、S. Chatterjee、W. Wolf

  DOI：10.1016/s0022-1139(00)82356-8

  日期：1991.12

  3′-Fluoro-3′-deoxy-thymidine (FDT), a fluorinated analog of 3′-azido-thymidine (AZT), is both more active against the HIV virus but also more toxic than AZT. Because of its fluorine atom, it can be labeled with 18F to be used to monitor this drug's biodistribution and targeting. A new synthesis for FDT, suited for 18F labeling, has been developed. After protecting the 5′-hydroxy group with a trityl

  3'-叠氮基胸苷（AZT）的氟化类似物3'-Fluoro-3'-脱氧胸苷（FDT）对HIV病毒更具活性，但比AZT毒性更大。由于它具有氟原子，因此可以用18 F标记，以监测该药物的生物分布和靶向性。已经开发出适用于18 F标记的FDT的新合成方法。在用三苯甲基保护5'-羟基后，将3'-羟基用Lyxo构型的甲磺酰基取代。用18 F氟化钾和Crown-18醚处理可得到18 F标记的氟代衍生物，在去三苯甲基化后可得到18 FF FDT具有7％的标记效率。这是首次报道使用氟化钾合成3'-氟-5'-O-三苯甲基脱氧胸苷并制备其18 F标记的类似物。在中间体化合物中掺入18 F并分离终产物所需的时间相当短（大约2小时），这将有足够的时间对这种短寿命的放射性核素进行生物学研究。
• Hydrofluorination of anhydrothymidine via soluble aluminum derivatives
  作者：Kenneth Green、David M. Blum

  DOI：10.1016/s0040-4039(00)71244-5

  日期：1991.5

  A new method to stereospecifically hydrofluorinate anhydrothymidine has been discovered which allows the product to be obtained in higher yields than the current literature method.