6-chloro-9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)-9H-purine | 132722-95-3

• 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-chloro-9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)-9H-purine
• 英文别名: 2-Cl-2'-F-ddP；[(2S,4S,5R)-5-(6-chloropurin-9-yl)-4-fluorooxolan-2-yl]methanol
• CAS: 132722-95-3
• 化学式: C₁₀H₁₀ClFN₄O₂
• 分子量: 272.666
• InChiKey: DZZDUTMJKITBNC-JFWOZONXSA-N

物化性质

• 沸点：
  488.7±55.0 °C(Predicted)
• 密度：
  1.82±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 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：
  73.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-chloro-9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)-9H-purine 在 氨 作用下， 以 甲醇 、 甲苯 为溶剂， 40.0~60.0 ℃ 、500.01 kPa 条件下， 反应 120.0h， 以1.6 g的产率得到2'-beta-氟-2',3'-二脱氧腺苷
  参考文献：
  名称：

  经由嘌呤3'-脱氧核苷合成9-（2,3-二脱氧-2-氟-β-D-苏-戊呋喃糖基）腺嘌呤（FddA）。

  摘要：

  经由6-氯-9-（3-脱氧-β-D-赤型-五氟呋喃糖基）合成9-（2,3-二脱氧-2-氟-β-D-苏-五呋喃糖基）腺嘌呤（1，FddA）描述了易于从肌苷（5）获得的）-9H-嘌呤（9）。通过引入6-氯基团可以改善嘌呤3'-脱氧核苷的C2'-β位置与三乙二氨基氨基硫的氟化作用，并且产率中等。嘌呤3'-脱氧核苷衍生物也与三乙胺三氟化氢进行亲核反应，并以良好的收率得到所需的氟化核苷。通过使用三乙胺三氟化氢大大提高了氟化工艺的安全性和产率。

  DOI：

  10.1021/jo0158985
• 作为产物：
  描述：

  5-(羟基甲基)二氢-2(3H)-呋喃酮 在 bismuth(III) bromide 、 三甲基溴硅烷 、 二乙胺基三氟化硫 、 MeOPH Jacobsen's catalyst 、 二异丁基氢化铝 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 72.0h， 生成 6-chloro-9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)-9H-purine
  参考文献：
  名称：

  A concise synthesis of anti-viral agent F-ddA, starting from (S)-dihydro-5-(hydroxymethyl)-2(3H)-furanone

  摘要：

  Anti-HIV agent beta-F-ddA (1) has been synthesized starting from readily available non-sugar, (S)-(+)-Dihydro-5-(hydroxymethyl)-2-(3H)-furanone (4). A highly sa n-stereoselective fluorination of the hydroxy lactone 2 generates the key intermediate fluorolactone 5 in a short and concise synthetic sequence. Reduction of 5 followed by bromination generates the aglycon which is glycosylated to generate F-ddA by amination and deprotection. Steric bulk of the 5-protecting group has minimal effect on the steric course of glycosylation. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)02532-7

文献信息

• Lipophilic, Acid-Stable, Adenosine Deaminase-Activated Anti-HIV Prodrugs for Central Nervous System Delivery. 2. 6-Halo- and 6-Alkoxy Prodrugs of 2'-.beta.-Fluoro-2',3'-dideoxyinosine
  作者：Harry Ford、Maqbool Siddiqui、John S. Driscoll、Victor E. Marquez、James A. Kelley、Hiroaki Mitsuya、Takuma Shirasaka

  DOI：10.1021/jm00007a015

  日期：1995.3

  and 6-alkoxy-(OMe-, OEt-) 9-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl) purines (F-ddN) have been synthesized and characterized with the objective of finding compounds which might be superior to existing drugs for the treatment of HIV in the central nervous system. These compounds, which contain lipophilic 6-substituents, were chosen as acid-stable prodrugs for the anti-HIV-active F-ddN, 9-(2,3

  一系列6卤代（F-，Cl-，Br-，I-）和6-烷氧基-（OMe-，OEt-）9-（2,3-二脱氧-2-氟-β-D-叔戊基呋喃糖基）嘌呤（F-ddN）已被合成和表征，目的是发现在中枢神经系统中治疗HIV可能优于现有药物的化合物。这些含有亲脂性6位取代基的化合物被选作抗HIV活性F-ddN，9-（2,3-二脱氧-2-氟-β-D-苏-五呋喃糖基）次黄嘌呤的酸稳定前药（F-ddI），因为相对于F-ddI，它们具有增加血脑屏障渗透的潜力。所有新化合物均比目前批准的抗艾滋病药物更具亲脂性。相对于二羟肌苷（ddI），对于6-氯-和6-乙氧基类似物，分配系数增加了30倍和110倍。2' -氟取代消除了pH 1，核苷糖基键的酸催化裂解。然而，在pH 1时，观察到6-氟取代基的酸催化水解产生F-ddI的速率约为t1 / 2（0.54 h）。比其他前药快40-170倍。F-ddN作为F-ddI的前药的效用取决
• Lipophilic, Acid-Stable, Adenosine Deaminase-Activated Anti-HIV Prodrugs for Central Nervous System Delivery. 3. 6-Amino Prodrugs of 2‘-β-Fluoro-2‘,3‘-dideoxyinosine
  作者：John S. Driscoll、Maqbool A. Siddiqui、Harry Ford,、James A. Kelley、Jeri S. Roth、Hiroaki Mitsuya、Masatoshi Tanaka、Victor E. Marquez

  DOI：10.1021/jm9509197

  日期：1996.1.1

  dimethylamino compounds are ca. 100 times more lipophilic than ddI or F-ddI. As expected, 2'-fluoro substitution protects the compounds from acid-catalyzed glycosylic cleavage. Only the hydroxylamino and nitro analogs underwent any nonenzymatic hydrolysis at pH 1.0 or 7.4. This reaction, however, results in hydrolysis of the group in the 6-position rather than glycosylic bond cleavage. ADA catalyzes

  合成并表征了一系列9-（2,3-二脱氧-2-氟-β-D-苏-五氟呋喃糖基）嘌呤（F-ddN）的6个取代氨基类似物，目的是发现可能是在治疗中枢神经系统中的HIV方面优于现有药物。这些化合物比目前批准的抗HIV药物具有更高的亲脂性，可以更好地渗透血脑屏障。随后腺苷脱氨酶（ADA）催化的这些前药在大脑中的水解可产生抗HIV药物9-（2,3-二脱氧-2-氟-β-D-苏-五呋喃糖基）次黄嘌呤（F- ddI）。由相应的6-氯类似物合成的新化合物包括F-ddN，其中含有甲基氨基，乙基氨基，二甲基氨基，羟基氨基，甲氧基氨基，苄氧基氨基，肼基，和在6-位的硝基取代基。在制备6-氯衍生物的过程中，以意外产物的形式分离了6-硝基类似物。在具有抗HIV活性的类似物中，乙氨基和二甲氨基化合物为约。亲脂性比ddI或F-ddI高100倍。如所预期的，2'-氟取代保护化合物免受酸催化的糖基裂解。在pH 1.0或7.4下，
• Therapeutic azide compounds
  申请人：University of Georgia Research Foundation, Inc.

  公开号：US20010036930A1

  公开（公告）日：2001-11-01

  Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.

  提供了药物前药组成物，其中包括具有可在体内转化为药物的药物的偶氮衍生物。具有胺基，酮基和羟基取代基的药物的偶氮衍生物在体内转化为相应的药物，增加了药物的半衰期。此外，偶氮前药通常比相应的药物更能穿过血脑屏障。特别有用的是cordycepin，2'-F-ara-ddI，AraA，acyclovir，penciclovir和相关药物的偶氮衍生物。有用的偶氮前药是治疗性脂环烷胺，酮和羟基取代化合物的偶氮衍生物，包括芳基烷基，杂环芳基烷基和环状脂肪族化合物，其中胺基或氧原子基团位于环上，或胺基或氧原子基团位于脂肪侧链上，以及治疗性嘌呤和嘧啶，核苷类似物和磷酸化核苷类似物。
• 2'-fluorofuranosyl derivatives and novel method of preparing
  申请人：The United States of America as represented by the Department of Health

  公开号：US05336764A1

  公开（公告）日：1994-08-09

  A compound has the formula ##STR1## wherein R is selected from the group consisting of (C.sub.7 -C.sub.20)aroyl, (C.sub.6 -C.sub.20)aryl, aralkyl and alkylaryl, and (C.sub.1 -C.sub.10)alkyl-di(C.sub.6 -C.sub.20)aryl Si, R' is selected from the group consisting of (C.sub.1 -C.sub.10)alkyl, (C.sub.7 -C.sub.20)aroyl and (C.sub.2 -C.sub.12)acyl, all of which may be further substituted with O, S, N or alkyl, and R'" is selected from the group consisting of halogen, (C.sub.1 -C.sub.10)alkoxy, (C.sub.1 -C.sub.10)acyloxy, O-methane-sulfonyl and O-p-toluenesulfonyl. A composition of matter comprises 0.001 to 99.999 wt % of the above compound.

  一种化合物的化学式为##STR1##其中R从以下组中选择：(C.sub.7 -C.sub.20)芳酰基，(C.sub.6 -C.sub.20)芳基，芳基烷基和烷基芳基，以及(C.sub.1 -C.sub.10)烷基-二(C.sub.6 -C.sub.20)芳基硅，R'从以下组中选择：(C.sub.1 -C.sub.10)烷基，(C.sub.7 -C.sub.20)芳酰基和(C.sub.2 -C.sub.12)酰基，所有这些都可以进一步用O、S、N或烷基取代，R'"从以下组中选择：卤素、(C.sub.1 -C.sub.10)烷氧基、(C.sub.1 -C.sub.10)酰氧基、O-甲烷磺酰基和O-p-甲苯磺酰基。一种物质组成包括上述化合物的0.001至99.999重量百分比。
• 2'-Fluorofuranosyl derivatives and methods for preparing
  申请人：The United States of America as represented by the Department of Health

  公开号：US05817799A1

  公开（公告）日：1998-10-06

  A method of preparing a 2'-fluoro compound of the formula ##STR1## where B is selected from the group consisting of purines and pyrimidines, both of which may be substituted, comprises reacting a compound of the formula II(a) or II(b) ##STR2## where R and R' are as defined in the specification with an acid halide under conditions effective to obtain a halide of the formula ##STR3## where X is a halogen. A silane of the formula B-Si (R").sub.3 where R" is as defined in the specification, is added to this product (III) under conditions effective to obtain a compound of the formula (IV) ##STR4## The compound of formula (IV) is reacted with a reagent selected from the group consisting of ammonia, BCl.sub.3 and ((C.sub.1 -C.sub.10)alkyl).sub.4 NF, under conditions effective to obtain the compound of formula (I). The compounds of formula (I) resulting from these methods exhibit anti-HIV activities and are useful for therapy against the HIV virus.

  一种制备公式为##STR1##的2'-氟化合物的方法，其中B选择自嘌呤和嘧啶的群，两者都可以被取代，包括以下步骤：将公式II（a）或II（b）的化合物##STR2##其中R和R'如规范中所定义，与酸卤反应，条件有效以获得公式##STR3##其中X为卤素。在此产物（III）中添加公式B-Si（R"）.sub.3的硅烷，其中R"如规范中所定义，条件有效以获得公式（IV）的化合物##STR4##公式（IV）的化合物与从群组中选择的试剂反应，该群组包括氨，BCl.sub.3和（（C.sub.1-C.sub.10）烷基）.sub.4NF，条件有效以获得公式（I）的化合物。由这些方法得到的公式（I）的化合物表现出抗HIV活性，并且对于治疗HIV病毒是有用的。