6-amino-2-chloro-9-(2-deoxy-α-D-erythro-pentofuranosyl)purine | 5542-92-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-amino-2-chloro-9-(2-deoxy-α-D-erythro-pentofuranosyl)purine
• 英文别名: 2-chloro-2'-deoxy-α-adenosine；1-(6-amino-2-chloro-purin-9-yl)-α-D-erythro-1,2-dideoxy-pentofuranose；2-Chlor-6-amino-9-<2'-desoxy-α-D-ribofuranosyl>-purin；6-Amino-2-chlor-9-<2'-desoxy-α-D-ribofuranosyl>-purin；1'-epi-Cladribine；(2R,3S,5S)-5-(6-amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 5542-92-7
• 化学式: C₁₀H₁₂ClN₅O₃
• 分子量: 285.69
• InChiKey: PTOAARAWEBMLNO-JKUQZMGJSA-N

物化性质

• 熔点：
  >173°C (dec.)
• 沸点：
  597.6±60.0 °C(Predicted)
• 密度：
  2.03±0.1 g/cm3(Predicted)
• 溶解度：
  酸水溶液（微溶、超声处理）、DMF（微溶、超声处理）、DMSO（微溶）、

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 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：
  7

反应信息

• 作为反应物：
  描述：

  6-amino-2-chloro-9-(2-deoxy-α-D-erythro-pentofuranosyl)purine 、 sodium methylate 以 甲醇 为溶剂， 以37%的产率得到2-methoxy-2'-deoxy-α-adenosine
  参考文献：
  名称：

  高效液相色谱/质谱法表征克拉屈滨及其相关化合物。

  摘要：

  高效液相色谱/质谱仪（HPLC / MS）用于鉴定和结构表征散装药物中修饰的核苷克拉屈滨（2-氯-2'-脱氧-β-腺苷）和13种与合成相关的副产物。通过从原料药的粗混合物中分离出的相关化合物进行光谱分析（1H和13C NMR光谱，质谱和UV吸收光谱），并通过使用真实标准品进行加标实验，可以确认化合物的身份。在线质谱分析（即LC / MS）的使用可增强UV吸收光谱，从而可以快速鉴定许多目标化合物。

  DOI：

  10.1002/jps.2600830416
• 作为产物：
  描述：

  在 甲醇 、 sodium methylate 作用下， 以87 %的产率得到6-amino-2-chloro-9-(2-deoxy-α-D-erythro-pentofuranosyl)purine
  参考文献：
  名称：

  远程参与立体定向氧化膦直接合成α-和β-2′-脱氧核苷

  摘要：

  2′-脱氧核苷及其类似物在药物开发中发挥着至关重要的作用，但其制备仍然是一个重大挑战。先前的研究主要集中在具有天然β构型的β-2′-脱氧核苷。事实上，它们的异构体α-2′-脱氧核苷也表现出多种生物活性和更好的代谢稳定性。在此，我们报道使用远程定向二苯基膦酰基（DPP）基团可以高产率和立体选择性地制备α-和β-2'-脱氧核苷。使用易于获得的 3,5-二-ODPP 供体制备 α-2'-脱氧核苷特别有效。在我们之前的同步面部O-糖基化研究中，氧化膦部分不是充当2-（二苯基膦酰基）乙酰基（DPPA）基团上的氢键受体，而是充当远程参与基团，以实现高度反面部的N-糖基化。这种提出的远程参与机制得到了我们通过变温核磁共振波谱对重要的 1,5-桥P杂双环中间体的首次表征的支持。有趣的是，抗增殖测定导致α-2'-脱氧核苷对中枢神经系统肿瘤细胞系SH-SY5Y和LN229的IC 50值在低微摩尔范围内，而其β-端基异构体在100

  DOI：

  10.1021/jacs.4c01780

文献信息

• Selective Preparations of Purine Nucleosides and Nucleotides: Reagents and Methods
  申请人：Zhong Minghong

  公开号：US20150376219A1

  公开（公告）日：2015-12-31

  A process of regiospecific synthesis of N-9 purine nucleoside analogs in either solution or solid phase synthesis is described. The introduction of the sugar moiety or its analogue on to a 6-heteroarylium purine or its mesomeric betaine so that formation of only the N-9 position regioisomers of the purine nucleoside analogs (either D or L enantiomers) is obtained. This regiospecific introduction of the sugar moiety allows the synthesis of purine nucleoside analogs in high yields without formation of the N-7-positional regioisomers, while the 6-heteroaryliums are leaving groups facilitated for nucleophilic displacement. Solid supported 6-heterarylium purine bases can be used for purine based library synthesis and synthesis of nucleotide monophosphates and polyphosphates. Processes for providing novel 6-heteroarylium purines and their corresponding mesomeric betaines for the regiospecific synthesis of N-9 purine nucleoside analogs and nucleotides are described.

  描述了一种在溶液或固相合成中合成N-9嘌呤核苷类似物的位置特异性合成过程。将糖基或其类似物引入到6-杂环嘌呤或其共振甲基盐上，从而仅形成嘌呤核苷类似物的N-9位置异构体（D或L对映体）。这种糖基的位置特异性引入允许在高产率下合成嘌呤核苷类似物，而不形成N-7位置异构体，而6-杂环嘌呤是易于亲核置换的离去基团。固相支持的6-杂环嘌呤碱可以用于嘌呤基库合成和核苷酸一磷酸和多磷酸的合成。描述了提供新颖的6-杂环嘌呤及其相应的共振甲基盐以用于N-9嘌呤核苷类似物和核苷酸的位置特异性合成的过程。
• Process for the preparation of 9-beta-anomeric nucleoside analogs
  申请人：Ash Stevens, Inc.

  公开号：US20040039190A1

  公开（公告）日：2004-02-26

  A process for substantially enhancing the regio and stereoselective synthesis of 9-&bgr;-anomeric nucleoside analogs is described. The introduction of the sugar moiety onto a 6-substituted purine base was preformed so that only the 9-&bgr;-D- or L-purine nucleoside analogs were obtained. This regio and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs and in particular 2′-deoxy, 3′-deoxy, 2′-deoxy-2′-&bgr;-fluoro and 2′,3′-dideoxy-2′-&bgr;-fluoro purine nucleoside analogs in high yield without virtually any formation of the 7-positional isomers. The compounds are drugs or intermediates to drugs.

  本文描述了一种显著增强9-β-异构核苷类似物的区域和立体选择性合成的过程。将糖基引入6-取代嘌呤碱基中，仅制备得到9-β-D-或L-嘌呤核苷类似物。这种区域和立体选择性引入糖基的方法允许高产率地合成核苷类似物，特别是2'-脱氧，3'-脱氧，2'-脱氧-2'-β-氟和2'，3'-二脱氧-2'-β-氟嘌呤核苷类似物，几乎不形成7-位异构体。这些化合物是药物或药物中间体。
• Methods For Selective N-9 Glycosylation of Purines
  申请人：Robins Morris J.

  公开号：US20080207891A1

  公开（公告）日：2008-08-28

  A process for providing regiospecific and highly stereoselective synthesis of 9-β anomeric purine nucleoside analogs is described. The introduction of the sugar moiety on to 6-(azolyl)-substituted purine bases is performed so that highly stereoselective formation of the β anomers of only the 9 position regioisomers of the purine nucleoside analogs (either D or L enantiomers) is obtained. This regiospecific and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs, and in particular 2′-deoxy, 3′-deoxy, 2′-deoxy-2′-halo-arabino and 2′,3′-dideoxy-2′-halo-threo purine nucleoside analogs, in high yields without formation of the 7-positional regioisomers. Processes for providing novel 6-(azolyl)purines for the regiospecific and highly stereoselective synthesis of 9-β anomeric purine nucleoside analogs are described. The compounds are drugs or intermediates to drugs.

  本文描述了一种提供9-β异构嘌呤核苷类似物的区域特异性和高度立体选择性合成的方法。将糖基引入到6-(咪唑基)-取代的嘌呤碱基上，以获得嘌呤核苷类似物的β异构体的高度立体选择性形成（D或L对映体）。这种区域特异性和立体选择性引入糖基的方法，允许高产率地合成核苷类似物，特别是2'-去氧、3'-去氧、2'-去氧-2'-卤代阿拉伯糖和2',3'-二去氧-2'-卤代-threo嘌呤核苷类似物，而不形成7位异构体。本文还描述了提供新型6-(咪唑基)嘌呤用于区域特异性和高度立体选择性合成9-β异构嘌呤核苷类似物的方法。这些化合物是药物或药物中间体。
• METHOD FOR THE PREPARATION OF 2-HALO-2'-DEOXYADENOSINE COMPOUNDS FROM 2'-DEOXYGUANOSINE
  申请人：Robins Morris J.

  公开号：US20090270604A1

  公开（公告）日：2009-10-29

  The present invention is a method for preparing 2-halo-6-aminopurines, and more specifically for preparing the clinical agent cladribine (2-chloro-2′-deoxyadenosine, CldAdo, 4), a drug of choice against hairy-cell leukemia and other neoplasms, from 2-amino-6-oxopurines, which are readily obtained from the naturally occurring compound 2′-deoxyguanosine. According to the methods of the present invention, the 6-oxo group of a protected 2′-deoxyguanosine (1) is converted to a 6-(substituted oxy) leaving group, or alternatively to a 6-chloro leaving group, the 2-amino group is replaced with a 2-chloro group, the 6-(substituted oxy) leaving group, or alternatively the 6-chloro leaving group, is replaced with a 6-amino group or, alternatively, a 2,6-dichloro substituted compound is selectively replaced with a 6-amino group, and the protecting groups are removed.

  本发明涉及制备2-卤代-6-氨基嘌呤，更具体地说，从2-氨基-6-氧代嘌呤制备临床药物克拉德霉素（2-氯-2'-脱氧腺苷，CldAdo，4），这是针对毛细胞白血病和其他肿瘤的首选药物。2-氨基-6-氧代嘌呤可以从天然存在的2'-脱氧鸟苷中轻松获得。根据本发明的方法，保护的2'-脱氧鸟苷（1）的6-氧代基被转化为6-（取代氧）离去基，或者被转化为6-氯离去基，2-氨基被2-氯代基取代，6-（取代氧）离去基或6-氯离去基被6-氨基取代，或者选择性地用6-氨基取代2,6-二氯取代化合物，并去除保护基。
• Method for the preparation of 2-halo-2'-deoxyadenosine compounds for 2'-deoxyguanosine
  申请人：Robins J. Morris

  公开号：US20070032645A1

  公开（公告）日：2007-02-08

  The present invention is a method for preparing 2-halo-6-aminopurines, and more specifically for preparing the clinical agent cladribine (2-chloro-2′-deoxyadenosine, CldAdo, 4), a drug of choice against hairy-cell leukemia and other neoplasms, from 2-amino-6-oxopurines, which are readily obtained from the naturally occurring compound 2′-deoxyguanosine. According to the methods of the present invention, the 6-oxo group of a protected 2′-deoxyguanosine (1) is converted to a 6-(substituted oxy) leaving group, or alternatively to a 6-chloro leaving group, the 2-amino group is replaced with a 2-chloro group, the 6-(substituted oxy) leaving group, or alternatively the 6-chloro leaving group, is replaced with a 6-amino group or, alternatively, a 2,6-dichloro substituted compound is selectively replaced with a 6-amino group, and the protecting groups are removed.

  本发明涉及一种制备2-卤代-6-氨基嘌呤的方法，更具体地说，是从2-氨基-6-氧代嘌呤制备临床药物克拉德霉素（2-氯-2'-脱氧腺苷，CldAdo，4），这是一种用于治疗毛细胞白血病和其他肿瘤的首选药物。2-氨基-6-氧代嘌呤是从天然存在的2'-脱氧鸟苷中容易得到的。根据本发明的方法，保护的2'-脱氧鸟苷（1）的6-氧代基被转化为6-(取代氧)离去基，或者替代为6-氯离去基，2-氨基被替换为2-氯基，6-(取代氧)离去基或者6-氯离去基被替换为6-氨基或者2,6-二氯取代化合物被选择性地替换为6-氨基，并去除保护基。