2-氯-2'-脱氧-2'-氟腺苷 | 156357-18-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 2-氯-2'-脱氧-2'-氟腺苷
• 英文名称: 2-chloro-9-(2-deoxy-2-fluoro-β-D-ribofuranosyl)adenine
• 英文别名: 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine；2-chloro-2'-deoxy-2'-fluoroadenosine；2’-fluoro-2-chloroadenosine；clofarabine；2-Chloro-9-(2-deoxy-2-fluoro-beta-d-ribofuranosyl)adenine；(2R,3R,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
• CAS: 156357-18-5
• 化学式: C₁₀H₁₁ClFN₅O₃
• 分子量: 303.68
• InChiKey: WDDPHFBMKLOVOX-DXTOWSMRSA-N

物化性质

• 沸点：
  599.5±60.0 °C(Predicted)
• 密度：
  2.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-氯-2'-脱氧-2'-氟腺苷 在 吡啶 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 7.0h， 生成
  参考文献：
  名称：

  A cocktail therapeutic strategy based on clofarabine-containing aptamer-PROTAC for enhanced cancer therapy

  摘要：

  通过在母体 Aptamer-PROTACs 上引入治疗性核苷类似物尾部，设计并评估了一种 PROTAC 尾部系统（ApTCs-3X）。

  DOI：

  10.1039/d3cc02904b
• 作为产物：
  描述：

  1-O-acetyl-3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-ribofuranoside 在 乙醇 、 氨 、 对甲苯磺酸 作用下， 25.0~160.0 ℃ 、3.33 kPa 条件下， 反应 36.83h， 生成 2-氯-2'-脱氧-2'-氟腺苷
  参考文献：
  名称：

  Synthesis and Biologic Activity of Purine 2′-Deoxy-2′-fluoro-ribonucleosides

  摘要：

  The synthesis of 3,5-di-O-benzoyl-2-deoxy-2-fluoro-D-ribofuranosyl bromide (8) and its reaction with 2,6-dichloropurine by fusion and with mercuric cyanide catalysis is described. The resulting 2,6-dichloro-9-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-beta-D-ribofuranosyl)purine (13) was converted to the 2-fluoroadenine (16), the 2-chloroadenine (17), 2,6-diaminopurine (12), and guanine (14) nucleosides by standard procedures. These nucleosides were cytotoxic to a number of cell lines in culture. The 2-haloadenine nucleosides 16 and 17 gave modest increases in lifespan when tested against the P388 leukemia in mice.

  DOI：

  10.1080/15257779408013243

文献信息

• Enzymatic Synthesis of Therapeutic Nucleosides using a Highly Versatile Purine Nucleoside 2’‐DeoxyribosylTransferase from<i>Trypanosoma brucei</i>
  作者：Elena Pérez、Pedro A. Sánchez‐Murcia、Justin Jordaan、María Dolores Blanco、José Miguel Mancheño、Federico Gago、Jesús Fernández‐Lucas

  DOI：10.1002/cctc.201800775

  日期：2018.10.9

  selected as the best derivative (4200 IU/g, activity recovery of 22 %), and could be easily recaptured and recycled for >25 reactions with negligible loss of activity. Finally, MTbPDT3 was successfully employed in the expedient synthesis of several nucleoside analogues. Taken together, our results support the notion that TbPDT has good potential as an industrial biocatalyst for the synthesis of a wide range

  与多步化学方法相比，使用酶来合成核苷类似物具有多个优势，包括化学，区域和立体选择性以及较温和的反应条件。本文报道了来自布鲁氏锥虫的嘌呤核苷2'-脱氧核糖基转移酶（PDT）的生产，表征和利用。Tb PDT是一种二聚体，不仅在很宽的温度范围（50–70°C），pH（4–7）和离子强度（0–500 mM NaCl）范围内都显示出出色的活性和稳定性，而且在高温下具有非凡的高稳定性碱性条件（pH 8-10）。bPDT被证明可以熟练地合成许多治疗性核苷，包括去羟肌苷，维达拉滨，克拉屈滨，氟达拉滨和奈拉拉滨。用Ala或Ser进行结构指导的Val11置换，导致变体的活性提高了2.8倍。Tb PDT也共价固定在戊二醛激活的磁性微球上。选择了M Tb PDT3作为最佳衍生物（4200 IU / g，活性回收率为22％），可以轻松地将其重新捕获和再循环用于> 25个反应，而活性损失可忽略不计。最后，男铽PDT3
• Method for synthesizing 2-chloro-9-(2-fluoro-beta-d-arabinofuranosyl)-9h-purin-6-amine
  申请人：——

  公开号：US20030023078A1

  公开（公告）日：2003-01-30

  2-Chloro-9-(2-deoxy-2-fluoro-&bgr;-D-arabinofuranosyl)-9H-purin-9-amine is synthesized by reacting a 2-chloro-6-substituted purine with a protected and activated 2-deoxy-2-fluoro-D-arabinofuranose; and reacting with a base such as ammonia to provide 2-chloro-9-(2-deoxy-2-fluoro-&bgr;-D-arabinofuranosyl)-9H-purin-6-amine. When the purine reactant is substituted in the 6 position with a halogen, a reaction step with an alkoxide is carried out prior to the reaction with ammonia.

  2-氯-9-(2-脱氧-2-氟-&bgr;-D-阿拉伯糖呋喃核苷基)-9H-嘌呤-9-胺是通过将2-氯-6-取代嘌呤与受保护和活化的2-脱氧-2-氟-D-阿拉伯糖呋喃糖反应，并与氨等碱反应而合成的。当嘌呤反应物在6位取代卤素时，在与氨反应之前进行一步与碱金属醇反应的步骤。
• [EN] METHODS FOR SYNTHESIZING 2-CHLORO-9-(2-DEOXY-2-FLUORO- beta -D-ARABINOFURANOSYL)-9H-PURIN-6-AMINE<br/>[FR] PROCEDES DE SYNTHESE DE 2-CHLORO-9-(2-DEOXY-2-FLUORO- DOLLAR G(B)-D-ARABINOFURANOSYL)-9H-PURINE-6-AMINE
  申请人：SOUTHERN RES INST

  公开号：WO2001060383A1

  公开（公告）日：2001-08-23

  2-Chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-9-amine is synthesized by reacting a 2-chloro-6-substituted purine with a protected and activated 2-deoxy-2-fluoro-D-arabinofuranose; and reacting with a base such as ammonia to provide 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine. When the purine reactant is substituted in the 6 position with a halogen, a reaction step with an alkoxide is carried out prior to the reaction with ammonia.

  2-氯-9-(2-去氧-2-氟-β-D-阿拉伯糖呋喃核苷基)-9H-嘌呤-9-胺是通过将2-氯-6-取代嘌呤与受保护和活化的2-去氧-2-氟-D-阿拉伯糖呋喃糖反应，并与氨等碱基反应而合成的。当嘌呤反应物在6位被卤素取代时，必须在与氨反应之前进行一步与碱金属醇反应的反应步骤。
• [EN] 2-HALO-9-(2-DEOXY-2-FLUORO-B-D-ARABINOFURANOSYL) ADENINE NUCLEOSIDE DERIVATIVES
  申请人：SOUTHERN RESEARCH INSTITUTE

  公开号：WO1990014352A1

  公开（公告）日：1990-11-29

  (EN) There are disclosed nucleosides having formula (I), wherein Z is F, Cl or Br and R is H or aryl. These compounds have anticancer activity.(FR) l'invention concerne des nucléosides ayant la forme (I) dans laquelle Z représente F, Cl ou Br et R représente H ou aryle. Ces composés présentent une activité anticancéreuse.

  （中）公开了具有式（I）的核苷，其中Z为F，Cl或Br，R为H或芳基。这些化合物具有抗癌活性。
• ２−クロロ−９−（２−デオキシ−２−フルオロ−β−Ｄ−アラビノフラノシル）−９Ｈ−プリン−６−アミンの合成方法
  申请人：——

  公开号：JP2010070560A

  公开（公告）日：2010-04-02

  PROBLEM TO BE SOLVED: To provide a method for synthesizing a 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine-6-amine in a comparatively high yield.

  SOLUTION: In the method for synthesizing a 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine-6-amine, (a) an anion of 2-chloro-6-substituted purine (here, the substituent of the 6-position of the 2-chloro-6-substituted purine is selected from the group consisting of an amino group and a protected amino group) is reacted with protected and activated 2-deoxy-2-fluoro-D-arabinofuranose and then with (b) ammonia to obtain 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine-6-amine.

  COPYRIGHT: (C)2010,JPO&INPIT

  需要解决的问题：提供一种在相对较高产率下合成2-氯-9-(2-去氧-2-氟-β-D-阿拉伯糖呋喃核苷)-9H-嘌呤-6-胺的方法。 解决方案：在合成2-氯-9-(2-去氧-2-氟-β-D-阿拉伯糖呋喃核苷)-9H-嘌呤-6-胺的方法中，(a) 2-氯-6-取代嘌呤的阴离子（此处，2-氯-6-取代嘌呤的6位取代基被选择为氨基基团和保护氨基基团的群）与保护和活化的2-去氧-2-氟-D-阿拉伯糖呋喃糖苷反应，然后与(b) 氨反应，以获得2-氯-9-(2-去氧-2-氟-β-D-阿拉伯糖呋喃核苷)-9H-嘌呤-6-胺。 版权所有：(C)2010，JPO&INPIT