(2R,3R,4S,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate | 5987-73-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3R,4S,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate
• 英文别名: 6-chloro-9-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)purine；6-chloro-9-(tri-O-acetyl-β-D-arabinofuranosyl)purine；6-chloropurine triacetylarabinopyranoside；tri-O-acetyl-1-(6-chloro-purin-9-yl)-β-D-1-deoxy-arabinofuranose；6-Chloro-9-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)purine；[(2R,3R,4S,5R)-3,4-diacetyloxy-5-(6-chloropurin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 5987-73-5；52921-33-2；63248-70-4
• 化学式: C₁₆H₁₇ClN₄O₇
• 分子量: 412.787
• InChiKey: INOTYVPMBNDAFK-YGSHXTJESA-N

物化性质

• 沸点：
  560.9±60.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  10

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate 在 叠氮化锂 、 氨 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 9-(β-D-arabinofuranosyl)-6-azidopurine
  参考文献：
  名称：

  Synthesis, Biotransformation, and Pharmacokinetic Studies of 9-(β-d-Arabinofuranosyl)-6-azidopurine:  A Prodrug for Ara-A Designed To Utilize the Azide Reduction Pathway

  摘要：

  As a part of our efforts to design prodrugs for antiviral nucleosides, 9-(beta-4-arabinofuranosyl)-6-azidopurine (6-AAP) was synthesized as a prodrug for ara-A that utilizes the azide reduction biotransformation pathway. 6-AAP was synthesized from ara-A via its 6-chloro analogue 4. The bioconversion of the prodrug was investigated in vitro and in vivo, and the pharmacokinetic parameters were determined. For in vitro studies, 6-AAP was incubated in mouse serum and liver and brain homogenates. The half-lives of 6-AAP in serum and liver and brain homogenates were 3.73, 4.90, and 7.29 h, respectively. 6-AAP was metabolized primarily in the liver homogenate microsomal fraction by the reduction of the azido moiety to the amine, yielding ara-A. However, 6-AAP was found to be stable to adenosine deaminase in a separate in vitro study. The in vivo metabolism and disposition of ara-A and 6-AAP were conducted in mice. When 6-AAP was administered by either oral or intravenous route, the half-life of ara-A was 7-14 times higher than for ara-A administered intravenously. Ara-A could not be found in the brain after the intravenous administration of ara-A. However, after 6-AAP administration (by either oral or intravenous route), significant levels of ara-A were found in the brain. The results of this study demonstrate that 6-AAP is converted to ara-A, potentially increasing the half-life and the brain delivery of ara-A. Further studies to utilize the azide reduction approach on other clinically useful agents containing an amino group are in progress in our laboratories.

  DOI：

  10.1021/jm960339p
• 作为产物：
  描述：

  2',3',5'-tri-O-acetyl-β-arahypoxanthine 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 生成 (2R,3R,4S,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate
  参考文献：
  名称：

  Synthesis, Biotransformation, and Pharmacokinetic Studies of 9-(β-d-Arabinofuranosyl)-6-azidopurine:  A Prodrug for Ara-A Designed To Utilize the Azide Reduction Pathway

  摘要：

  As a part of our efforts to design prodrugs for antiviral nucleosides, 9-(beta-4-arabinofuranosyl)-6-azidopurine (6-AAP) was synthesized as a prodrug for ara-A that utilizes the azide reduction biotransformation pathway. 6-AAP was synthesized from ara-A via its 6-chloro analogue 4. The bioconversion of the prodrug was investigated in vitro and in vivo, and the pharmacokinetic parameters were determined. For in vitro studies, 6-AAP was incubated in mouse serum and liver and brain homogenates. The half-lives of 6-AAP in serum and liver and brain homogenates were 3.73, 4.90, and 7.29 h, respectively. 6-AAP was metabolized primarily in the liver homogenate microsomal fraction by the reduction of the azido moiety to the amine, yielding ara-A. However, 6-AAP was found to be stable to adenosine deaminase in a separate in vitro study. The in vivo metabolism and disposition of ara-A and 6-AAP were conducted in mice. When 6-AAP was administered by either oral or intravenous route, the half-life of ara-A was 7-14 times higher than for ara-A administered intravenously. Ara-A could not be found in the brain after the intravenous administration of ara-A. However, after 6-AAP administration (by either oral or intravenous route), significant levels of ara-A were found in the brain. The results of this study demonstrate that 6-AAP is converted to ara-A, potentially increasing the half-life and the brain delivery of ara-A. Further studies to utilize the azide reduction approach on other clinically useful agents containing an amino group are in progress in our laboratories.

  DOI：

  10.1021/jm960339p

文献信息

• [EN] 6-ARYL-9-GLYCOSYLPURINES AND USE THEREOF<br/>[FR] 6-ARYL-9-GLYCOSYLPURINES ET LEUR UTILISATION
  申请人：UNIV PALACKEHO

  公开号：WO2016091236A1

  公开（公告）日：2016-06-16

  The present invention provides 6-aryl-9-glycosidpurines of general formula I and pharmaceutically acceptable salts thereof with alkali metals, ammonia, amines, or addition salts with acids, wherein Gly represents β-D-arabinofuranosyl or β-D-2´-deoxyribofuranosyl, Ar represents benzyl or furfuryl, each of which can be unsubstituted or substituted by one or more, preferably one to three, substituents selected from the group comprising hydroxyl, alkyl, halogen, alkoxy, amino, mercapto, carboxyl, cyano, amido, sulfo, sulfamido, acyl, acylamino, acyloxy, alkylamino, dialkylamino, alkylmercapto, trifluoromethyl, trifluoromethoxy, for use for regulation, in particular inhibition, of aging in plants in vivo or plant cells in vitro, and for regulation of growth and development of plants in vivo, plant tissues, plant organs and plant cells in vitro..

  本发明提供了通式I的6-芳基-9-糖苷嘌呤及其与碱金属、氨、胺或酸的加合盐，其中Gly代表β-D-阿拉伯呋喃糖苷或β-D-2´-脱氧核糖呋喃糖苷，Ar代表苄基或呋喃甲基，每个都可以是未取代的或被一个或多个，优选一个至三个，羟基、烷基、卤素、烷氧基、氨基、巯基、羧基、氰基、酰胺基、磺酰基、磺胺基、酰基、酰胺基、酰氧基、烷基氨基、二烷基氨基、烷基巯基、三氟甲基、三氟甲氧基等取代基所取代，用于调节植物体内或植物细胞体外的衰老，特别是抑制衰老，并用于调节植物体内、植物组织、植物器官和植物细胞体外的生长和发育。
• Efficient synthesis of nebularine and vidarabine via dehydrazination of (hetero)aromatics catalyzed by CuSO₄in water
  作者：Ran Xia、Ming-Sheng Xie、Hong-Ying Niu、Gui-Rong Qu、Hai-Ming Guo

  DOI：10.1039/c3gc41658e

  日期：——

  A simple dehydrazination reaction has been achieved in the presence of a catalytic amount of CuSO4 for the first time. With CuSO4 (2 mol%) as a catalyst and water as a solvent, the dehydrazination products were obtained in good yields (66–95%). Moreover, the drugs nebularine and vidarabine were afforded successfully, and vidarabine could be produced on a 0.923 kg scale, which shows good potential for industrial applications.

  首次在催化量的CuSO4存在下实现了一步简单的脱氢反应。以CuSO4 (2 mol%)为催化剂，水为溶剂，脱氢产物获得了良好的产率（66-95%）。此外，成功合成了药物 nebularine 和 Vidarabine，并且 Vidarabine 可在0.923公斤规模生产，显示出良好的工业应用潜力。
• Facilitating Rh-Catalyzed C–H Alkylation of (Hetero)arenes and 6-Arylpurine Nucleosides (Nucleotides) with Electrochemistry
  作者：Qi-Liang Yang、Ying Liu、Lei Liang、Zhi-Hao Li、Gui-Rong Qu、Hai-Ming Guo

  DOI：10.1021/acs.joc.2c00391

  日期：2022.5.6

  An electrochemical approach to promote the ortho-C–H alkylation of (hetero)arenes via rhodium catalysis under mild conditions is described. This approach features mild conditions with high levels of regio- and monoselectivity that tolerate a variety of aromatic and heteroaromatic groups and offers a widely applicable method for late-stage diversification of complex molecular architectures including

  描述了一种在温和条件下通过铑催化促进（杂）芳烃的邻-C-H 烷基化的电化学方法。这种方法具有温和的条件，具有高水平的区域选择性和单选择性，可耐受各种芳香族和杂芳香族基团，并为复杂分子结构的后期多样化提供了一种广泛适用的方法，包括色氨酸、雌酮、地西泮、核苷和核苷酸。烷基硼酸和酯以及烷基三氟硼酸盐被证明是合适的偶联配对物。关键铑中间体的分离和机理研究为铑（III/IV 或 V）方案提供了强有力的支持。
• Prodrug azide compositions and compounds
  申请人：University of Georgia Research Foundation Inc.

  公开号：US06271212B1

  公开（公告）日：2001-08-07

  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.

  提供了药物前药的制剂，其中包括可在体内转化为药物的药物的叠氮化衍生物。具有胺基，酮基和羟基取代基的药物的叠氮化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，叠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和相关药物的叠氮化衍生物。有用的叠氮前药是治疗性脂环胺，酮，羟基取代化合物的叠氮化衍生物，包括芳基烷基，杂环芳基烷基和环状脂肪族化合物，其中胺基或氧基团位于环上，或胺基或氧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。
• Rhodium(III)-Catalyzed Synthesis of Diverse Fluorescent Polycyclic Purinium Salts from 6-Arylpurine Nucleosides and Alkynes
  作者：Qi-Liang Yang、Ying Liu、Yi-Rui Luo、Zhi-Hao Li、Hong-Wei Jia、Ya-Bo Fu、Gui-Rong Qu、Hai-Ming Guo

  DOI：10.1021/acs.orglett.2c01546

  日期：2022.6.17

  RhIII-catalyzed C–H activation/annulation of 6-arylpurine nucleosides with alkynes under mild reaction conditions. The resulting products displayed tunable photoluminescence covering most of the visible spectrum. Mechanistic insights delineated the rhodium catalyst’s mode of action. A purinoisoquinolinium-coordinated rhodium(I) sandwich complex was well characterized and identified as the key intermediate

  本文描述了一种有效的策略，用于在温和的反应条件下通过 Rh III催化的 6-芳基嘌呤核苷与炔烃的 C-H 活化/环化来组装具有广泛阴离子的功能化多环嘌呤盐库。所得产品显示出覆盖大部分可见光谱的可调光致发光。机械见解描绘了铑催化剂的作用方式。purinoisoquinolinium 配位的铑 (I) 夹层复合物被很好地表征并确定为关键中间体。