6-Chloro-2-nitro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-9H-purine | 266360-68-3

• 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-2-nitro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-9H-purine
• 英文别名: 2-nitro-6-chloro-9-(2,3,5-triacetyl-β-D-ribofuranosyl)-9H-purine；acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(6-chloro-2-nitro-purin-9-yl)-tetrahydro-furan-3-yl ester；triacetoxy-2-nitro-6-chloroadenosine；6-chloro-9-(2,3,5-tri-O-acetate-ribose)-2-nitropurine；triacetoxy-6-chloro-2-nitro-adenosine；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(6-chloro-2-nitropurin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 266360-68-3
• 化学式: C₁₆H₁₆ClN₅O₉
• 分子量: 457.784
• InChiKey: HBATZLHDWJBPPG-SDBHATRESA-N

物化性质

• 沸点：
  664.7±65.0 °C(Predicted)
• 密度：
  1.76±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  31
• 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：
  178
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  6-Chloro-2-nitro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-9H-purine 在 sodium azide 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-amino-2-nitro-9-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-purine
  参考文献：
  名称：

  Regioselective nitration of purine nucleosides: synthesis of 2-nitroadenosine and 2-nitroinosine

  摘要：

  Nitration reactions of 6-substituted purine nucleosides with tetrabutylammonium nitrate/trifluoroacetic anhydride (TBAN/TFAA) have been studied. This nitrating mixture selectively nitrates C-6 substituted purines at the 2-position, but the method is limited to substrates without NH or OH substituents. Acetylated 6-chloropurine riboside was cleanly nitrated (DCM, 0 degrees C, 71%) and converted to nitro substituted adenosine and inosine in a few simple steps. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)02271-6
• 作为产物：
  描述：

  肌苷 在 4-二甲氨基吡啶 、 氯化亚砜 、 四甲基硝酸铵 、 三乙胺 、 N,N-二甲基甲酰胺 、 三氟乙酸酐 作用下， 以 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 19.5h， 生成 6-Chloro-2-nitro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-9H-purine
  参考文献：
  名称：

  [EN] ADENOSINE RECEPTOR AGONISTS
  [FR] COMPOSES THERAPEUTIQUES

  摘要：

  公开号：

  WO2005084653A3

文献信息

• Synthesis and properties of 2-nitrosoadenosine
  作者：Martin J. Wanner、Gerrit-Jan Koomen

  DOI：10.1039/b102897a

  日期：——

  A series of new 2-substituted adenosine derivatives was synthesised via addition and condensation reactions with 2-nitrosoadenosine triacetate 4. The exceptional reactivity of the adenosine nitroso functionality was demonstrated by reaction with, e.g., dienes (4 + 2 cycloaddition), cyclohexene (‘ene’ reaction), furans (addition/rearrangement) and with anilines (Mills coupling). 2-Nitrosoadenosine triacetate was prepared from 6-chloropurine riboside triacetate via nitration at the 2-position followed by reduction/oxidation of the nitro group. The vulnerable nitroso functionality of 4 had to be protected by 4 + 2 cycloaddition with cyclopentadiene to make deacylation of the ribose ring possible. Retro-Diels–Alder reaction of the deacylated product at 95 °C gave the title compound 2-nitrosoadenosine 7. Dimerisation of the nitroso functionality of triacetate 4 was studied with 1H NMR by changing the temperature, concentration and solvent. In particular, variation of temperature gave control over this dimerisation: 100% monomer at 65 °C gave complete dimerisation at −20 °C.

  一系列新的2取代腺苷衍生物是通过与2-亚硝基腺苷三乙酸酯4进行加成和缩合反应合成的。腺苷亚硝基功能团的优异反应性通过与烯烃（4 + 2环加成反应）、环己烯（“烯”反应）、呋喃（加成/重排反应）和苯胺（米尔斯偶联）等反应得到了证明。2-亚硝基腺苷三乙酸酯是通过对6-氯嘌呤核苷三乙酸酯进行2位的硝化反应，然后再对硝基进行还原/氧化反应合成的。4的脆弱亚硝基功能团需要通过与环戊二烯进行4 + 2环加成反应进行保护，以使RNA环的去酰化成为可能。在95°C下，去酰化产物的反向Diels-Alder反应生成了标题化合物2-亚硝基腺苷7。通过改变温度、浓度和溶剂，研究了三乙酸酯4的亚硝基功能团的二聚化过程。特别是，温度的变化对这种二聚化反应起到了控制作用：在65°C时为100%单体，在-20°C时则完全二聚化。
• 2-Substituted-6-trifluoromethyl purine derivatives with adenosine-A3 antagonistic activity
  申请人：Koch Melle

  公开号：US20060052331A1

  公开（公告）日：2006-03-09

  The present invention relates to 2-substituted-6-trifluoromethyl purine derivatives as selective adenosine antagonists, in particular adenosine-A 3 receptor antagonists, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said purine derivatives. The compounds have the general formula (1) wherein the symbols have the meanings given in the specification.

  本发明涉及作为选择性腺苷拮抗剂的2-取代-6-三氟甲基嘌呤衍生物，特别是腺苷A3受体拮抗剂，以及用于制备这些化合物的方法和用于合成所述嘌呤衍生物的新型中间体。这些化合物具有一般式（1），其中符号具有规范中给定的含义。
• [EN] IMPROVED SYNTHESIS OF 2-SUBSTITUTED ADENOSINES<br/>[FR] SYNTHESE AMELIOREE D'ADENOSINES 2-SUBSTITUEES
  申请人：CAMBRIDGE BIOTECHNOLOGY LTD

  公开号：WO2005054269A1

  公开（公告）日：2005-06-16

  A method of synthesis of a 2-substituted adenosine of formula I which comprises converting a compound of formula II to a compound of formula (I), wherein: R is C 1-6 alkoxy (straight or branched), a phenoxy group (unsubstituted, or mono-, or di-substituted by halo, amino, CF3-, cyano, nitro, C 1-6 alkyl, or C 1-6 alkoxy), a benzyloxy group (unsubstituted, or mono-, or di-substituted by halo, amino, CF3-, cyano, nitro, Cl_6 alkyl, or Cl_6 alkoxy), or a benzoyl group (unsubstituted, or mono-, or di-substituted by halo, amino, CF3-, cyano, nitro, C 1-6 alkyl, or C 1-6 alkoxy); R' = H, or a protecting group.

  一种合成式I的2-取代腺苷的方法，包括将式II的化合物转化为式(I)的化合物，其中：R为C 1-6烷氧基（直链或支链）、苯氧基（未取代或经氟、氨基、CF3-、氰基、硝基、C 1-6烷基或C 1-6烷氧基单取代或双取代）、苄氧基（未取代或经氟、氨基、 -、氰基、硝基、Cl_6烷基或Cl_6烷氧基单取代或双取代）或苯甲酰基（未取代或经氟、氨基、 -、氰基、硝基、C 1-6烷基或C 1-6烷氧基单取代或双取代）；R' = H或保护基。
• Solid phase synthesis of C2,N6-disubstituted adenosine analogues
  作者：Boris Rodenko、Martin J. Wanner、Gerrit-Jan Koomen

  DOI：10.1039/b201943d

  日期：2002.5.10

  A 6-step solid phase sequence towards C2,N6-disubstituted adenosine analogues was developed, which was validated by the construction of a small combinatorial library. Attachment of the 5′-OH of readily available 2′,3′-methoxymethylidene protected 6-chloropurine ribonucleoside onto carboxypolystyrene furnished the immobilised 6-chloropurine ribonucleoside. Nitration on the solid phase resulted in the formation of the 2-nitro-6-chloropurine nucleoside, a highly reactive difunctionalised species. Amines were selectively introduced at the 6-position by 6-chloro displacement at room temperature without affecting the 2-nitro group. Subsequent substitution of the 2-nitro group by amines was achieved at 80–90 °C. Removal of the methoxymethylidene group under mildly acidic conditions, followed by cleavage of the nucleosides from the resin, yielded the C2,N6-disubstituted adenosine analogues.

  开发了针对 C2,N6-二取代腺苷类似物的 6 步固相序列，并通过构建小型组合文库进行了验证。将容易获得的 2',3'-甲氧基亚甲基保护的 6-氯嘌呤核糖核苷的 5'-OH 连接到羧基聚苯乙烯上，得到固定化的 6-氯嘌呤核糖核苷。固相硝化导致形成 2-硝基-6-氯嘌呤核苷，这是一种高反应性双官能化物质。在室温下通过6-氯置换选择性地在6-位引入胺，而不影响2-硝基。随后在 80–90 °C 下实现了 2-硝基基团被胺的取代。在弱酸性条件下除去甲氧基亚甲基，然后从树脂上裂解核苷，得到 C2,N6-二取代的腺苷类似物。
• 一种以肌苷为原料合成2,6-二氯嘌呤核苷的 方法
  申请人：新乡学院

  公开号：CN105418710B

  公开（公告）日：2018-04-27

  本发明公开了一种以肌苷为原料合成2,6‑二氯嘌呤核苷的方法。本发明以廉价的肌苷为原料，通过乙酰化和氯代反应，得到6‑氯三乙酰嘌呤核苷，继而和三氟甲磺酸酐反应，在2位引入硝基，最后在被氯化氢气体饱和的乙醇溶液中，完成脱除乙酰基和硝基氯代两步反应，得到2,6‑二氯嘌呤核苷，总收率63％。本方法原料廉价易得，避免使用价格昂贵的试剂和有毒有害的重金属催化剂，且反应规模扩大到200g规模时，收率无明显下降。本发明为2,6‑二氯嘌呤核苷的合成提供了一条新的合成途径，具有潜在的应用前景。