5-O-苯甲酰基-3-叠氮基-3-脱氧胸腺嘧啶脱氧核苷 | 106060-78-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 5-O-苯甲酰基-3-叠氮基-3-脱氧胸腺嘧啶脱氧核苷
• 英文名称: 3'-azido-5'-benzoyl-3'-deoxythymidine
• 英文别名: 3'-azido-5'-O-benzoyl-3'-deoxthymidine；3'-azido-5'-O-benzoyl-3'-deoxythymidine；5'-benzoyl-3'-azido-3'-deoxythymidine；5'-benzoyl-AZT；5'-O-benzoyl-AZT；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl benzoate
• CAS: 106060-78-0
• 化学式: C₁₇H₁₇N₅O₅
• 分子量: 371.352
• InChiKey: VCEFTZVMYBTJNH-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  99.3
• 氢给体数：
  1
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  齐多夫定	3'-azido-2',3'-deoxythymidine	30516-87-1	C10H13N5O4	267.244
  ——	1-(5-O-benzoyl-2-deoxy-3-O-mesyl-β-D-xylofuranosyl)thymine	120932-43-6	C18H20N2O8S	424.431
  ——	((2R,3S,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-(methylsulfonyloxy)-tetrahydrofuran-2-yl)methyl benzoate	165047-02-9	C18H20N2O8S	424.431
  5-苯甲酰基-3-乙烷磺酰基-2-溴胸苷	5'-benzoyl-2'-α-bromo-3'-O-methanesulfonylthymidine	165047-01-8	C18H19BrN2O8S	503.327
  beta-胸苷	thymidine	146183-25-7	C10H14N2O5	242.232
  ——	2,3'-anhydro-5'-O-benzoyl-2'-deoxythymidine	70838-44-7	C17H16N2O5	328.324

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	5'-O-[(vinyloxy)carbonyl]-3'-azido-3'-deoxythymidine	775323-12-1	C13H15N5O6	337.292
  齐多夫定	3'-azido-2',3'-deoxythymidine	30516-87-1	C10H13N5O4	267.244
  ——	5'-[[N-[4-(2',3'-dideoxy-2',3'-didehydrothymidin-5'-yl)butyl]carbamoyl]oxy]-3'-azido-3'-deoxythymidine	——	C26H33N9O10	631.602
  ——	1-[(2R,4S,5S)-4-[4-(2-azidoethyl)triazol-1-yl]-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione	1313201-78-3	C14H18N8O4	362.348
  ——	1-[(2R,4S,5S)-4-[4-(3-azidopropyl)triazol-1-yl]-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione	1313201-79-4	C15H20N8O4	376.375
  ——	1-[(2R,4S,5S)-4-[4-(azidomethyl)triazol-1-yl]-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione	1313201-77-2	C13H16N8O4	348.321
  ——	5'-[[N-[4-(2',3'-dideoxy-2',3'-didehydrothymidin-5'-yl)butyl]carbamoyl]oxy]-2',3'-dideoxy-2',3'-didehydrothymidine	——	C26H32N6O10	588.574
  ——	4-amino-1-[(2R,4S,5S)-4-[4-(2-azidoethyl)triazol-1-yl]-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidin-2-one	1313201-86-3	C14H19N9O3	361.363
  ——	4-amino-1-[(2R,4S,5S)-4-[4-(3-azidopropyl)triazol-1-yl]-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidin-2-one	1313201-87-4	C15H21N9O3	375.39
  ——	4-amino-1-[(2R,4S,5S)-4-[4-(azidomethyl)triazol-1-yl]-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidin-2-one	1313201-85-2	C13H17N9O3	347.336

反应信息

• 作为反应物：
  描述：

  5-O-苯甲酰基-3-叠氮基-3-脱氧胸腺嘧啶脱氧核苷 在 氨 作用下， 以 甲醇 为溶剂， 以81%的产率得到齐多夫定
  参考文献：
  名称：

  一种甲基酮衍生物及其制备方法与应用

  摘要：

  本发明公开了一种甲基酮衍生物及其制备方法与应用，将酮衍生物、有机过氧化物溶于溶剂中，于80‑130℃反应，获得甲基嘧啶酮和甲基吡啶酮衍生物。本发明使用酮衍生物为起始物，原料易得、种类很多；利用本发明的方法得到的产物类型多样，既可以直接使用、又可以用于其他进一步的反应。本发明方法无金属参与，适合于制药工艺。本发明方法路线简短、反应条件温和、反应操作和后处理过程简单、产率较高，适合于规模化生产。

  公开号：

  CN106496130B
• 作为产物：
  描述：

  1-(5-O-benzoyl-2-deoxy-3-O-mesyl-β-D-xylofuranosyl)thymine 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以67%的产率得到5-O-苯甲酰基-3-叠氮基-3-脱氧胸腺嘧啶脱氧核苷
  参考文献：
  名称：

  Transformations of β-d-xylofuranosyl nucleosides. Synthesis of 3′-azido-3′-deoxythymidine

  摘要：

  A modified synthesis of 3'-azido-3'-deoxythymidine starting from D-xylose is proposed.

  DOI：

  10.1007/bf02494517

文献信息

• Synthesis of dinucleotides containing a bridged non-chiral internucleotide 5′- or 3′-phosphoramidate linkage
  作者：Matthias Mag、Joachim W. Engels

  DOI：10.1016/s0040-4020(01)81755-5

  日期：1994.8

  The synthesis of several dinucleoside phosphate derivatives which are linked by phosphoramidate bonds [3′-O-P(O)(O−)-NH-5′ or 3′-NH-P(O)(O−)-O-5′] has been accomplished. The internucleoside phosphoramidate linkage was performed using the Staudinger reaction which is directly followed by a Michaelis-Arbuzov type transformation. Due to the exclusive use of base labile blocking groups deprotection could

  通过氨基磷酸酯键[ 3'- O - P（= O）（O -）- NH -5'或3'- NH - P（= O）（O -）- O连接的几种二核苷磷酸酯衍生物的合成-5′]已经完成。使用Staudinger反应进行核苷间氨基磷酸酯键合，然后直接进行Michaelis-Arbuzov型转化。由于仅使用碱不稳定的封闭基团，因此可以非常简单地通过在55°C下用浓氨水处理24小时来轻松进行脱保护。
• An efficient synthesis of 3′-amino-3′-deoxythymidine derivatives
  作者：K. V. Seregin、M. V. Chudinov、A. M. Yurkevich、V. I. Shvets

  DOI：10.1007/s11171-005-0018-4

  日期：2005.3

  An efficient method of reduction of 3'-azido-3'-deoxythymidine and its 5'-protected derivatives to 3'-aminothymidine derivatives on a palladium catalyst using ammonium formate as a source of hydrogen was suggested.

  提出了在甲酸催化剂上使用甲酸铵作为氢源将3'-叠氮基3'-脱氧胸苷及其5'-保护的衍生物还原为3'-氨基胸苷衍生物的有效方法。
• Synthesis and Anti-HIV Evaluation of 3′-Triazolo Nucleosides
  作者：Vincent Roy、Aleksandr Obikhod、Hong-Wang Zhang、Steven J. Coats、Brian D. Herman、Nicolas Sluis-Cremer、Luigi A. Agrofoglio、Raymond F. Schinazi

  DOI：10.1080/15257770.2011.580291

  日期：2011.4

  A series of hitherto unknown 3'--[1,2,3]-substituted triazolo-2',3'-dideoxypyrimidine nucleoside analogues of the anti-HIV 3'-azido-3'-deoxythymidine (AZT) were synthesized through catalyzed alkyne-azide 1,3-dipolar cycloaddition (Huisgen reaction). Those 3'-[1,2,3]-triazolo analogues bearing an azido alkyl chain were evaluated for their anti-HIV activity against HIV-1 in primary human lymphocytes as well as for their cytotoxicity in different cells. None of them inhibit HIV replication (EC50 20 M); two of them were converted to their triphosphate form to evaluate their HIV-RT inhibition.
• Synthesis of Novel Branched Nucleoside Dimers Containing a 1,2,3-Triazolyl Linkage
  作者：Hassan. B. Lazrek、Joaachim. W. Engels、Wolfgang Pfleiderer

  DOI：10.1080/07328319808004722

  日期：1998.9

  Three branched nucleoside dimers containing a 1,2,3-triazole linkage have been synthesized using 1,3-dipolar cycloaddition of N-3 or C-5 acetylene nucleosides with 3'-azido3'-deoxythymidine.
• Synthesis and antiviral activity of 3'-heterocyclic substituted 3'-deoxythymidines
  作者：Piet Wigerinck、Arthur Van Aerschot、Gerard Janssen、Paul Claes、Jan Balzarini、Erik De Clercq、Piet Herdewijn

  DOI：10.1021/jm00164a063

  日期：1990.2

  Various 3'-deoxythymidine analogues with an heterocyclic five-membered ring in the 3'-erythro position have been synthesized. The pyrrol-1-yl (3) and the 1,2,4-triazol-4-yl (5) compounds were synthesized from 1-(3-amino-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine. The pyrazol-1-yl (16a), imidazol-1-yl (16b), and 1,2,4-triazol-1-yl (16c) derivatives were obtained by epoxide opening of the corresponding 1-(2,3-anhydro-beta-D-lyxofuranosyl)thymines followed by 2'-deoxygenation. Only the 3'-pyrrol-1-yl derivative showed marginal antiviral activity against human immunodeficiency virus.