(1S,2S,4S,5R)-9-[4-hydroxy-5-(hydroxymethyl)bicyclo[3.1.0]hex-2-yl]purin-6-one | 316380-46-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1S,2S,4S,5R)-9-[4-hydroxy-5-(hydroxymethyl)bicyclo[3.1.0]hex-2-yl]purin-6-one
• 英文别名: 9-[(1S,2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)-2-bicyclo[3.1.0]hexanyl]-1H-purin-6-one
• CAS: 316380-46-8
• 化学式: C₁₂H₁₄N₄O₃
• 分子量: 262.268
• InChiKey: LLMKVCMZHNLWBL-VXDIOVFMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  99.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1S,2S,4S,5R)-9-[4-hydroxy-5-(hydroxymethyl)bicyclo[3.1.0]hex-2-yl]purin-6-one 在 吡啶 、 乙酸酐 作用下， 以 甲醇 为溶剂， 生成 (1R,2S,4S,5S)-1-hydroxymethyl-2-hydroxy-4-(6-amino-9-purinyl)bicyclo<3.1.0>hexane
  参考文献：
  名称：

  A Remarkably Simple Chemicoenzymatic Approach to Structurally Complex Bicyclo[3.1.0]hexane Carbocyclic Nucleosides

  摘要：

  [GRAPHICS]Intramolecular cyclopropanation of a carbene engendered from the corresponding diazo beta -ketoester produced the desired bicyclo[3.1.0]hexane pseudosugar. Purine nucleosides obtained via Mitsunobu coupling were resolved with adenosine deaminase. The requisite beta -ketoester was assembled in one step from ethyl acetoacetate and acrolein.

  DOI：

  10.1021/ol000238s
• 作为产物：
  描述：

  6-chloro-9-{(1S,2S,4S,5R)-4-(phenylmethoxy)-5-[(phenylmethoxy)methyl]bicyclo[3.1.0]hex-2-yl}-9H-purine 在 三氯化硼 、 甲醇 作用下， 以 二氯甲烷 为溶剂， 反应 6.25h， 生成 (1S,2S,4S,5R)-9-[4-hydroxy-5-(hydroxymethyl)bicyclo[3.1.0]hex-2-yl]purin-6-one
  参考文献：
  名称：

  端基异构作用是否是腺苷脱氨酶催化嘌呤核苷水解速率的重要因素？在核糖和碳环模板上构建的核苷类似物与选择用来促进水合的等效杂环碱基的直接比较。

  摘要：

  （North）-methanocarbadeoxyadenosine [（N）-MCdA，（5）]的糖苷配基，相对较弱的腺苷脱氨酶（ADA）相对脱氨速率。比腺苷低100倍-在6位（6-氟，化合物6）和8位（8-氮杂，化合物7）处被取代，目的是提高水合度，从而提高ADA的水解度。在这些底物中，稠合的环丙烷部分约束环戊烷环以模拟假旋转周期北半球中呋喃糖的构象，这与腺苷与ADA复合形成的核糖环的构象相匹配。对ADA水解的敏感性顺序为腺苷>>（N）-MCdA（5）大约等于（N）-6F-MCdP（6）>（N）-8-氮杂-MCdA（7）。尽管已知8-氮杂腺苷的水解速度是腺苷的两倍，

  DOI：

  10.1016/s0968-0896(02)00099-8

文献信息

• Contrasting Behavior of Conformationally Locked Carbocyclic Nucleosides of Adenosine and Cytidine as Substrates for Deaminases
  作者：Victor E. Marquez、Gottfried K. Schroeder、Olaf R. Ludek、Maqbool A. Siddiqui、Abdallah Ezzitouni、Richard Wolfenden

  DOI：10.1080/15257770903091904

  日期：2009.8.11

  In addition to the already known differences between adenosine deaminase (ADA) and cytidine deaminase (CDA) in terms of their tertiary structure, the sphere of Zn+2 coordination, and their reverse stereochemical preference, we present evidence that the enzymes also differ significantly in terms of the North/South conformational preferences for their substrates and the extent to which the lack of the

  除了已知的腺苷脱氨酶 (ADA) 和胞苷脱氨酶 (CDA) 在三级结构、Zn+2 配位范围和反向立体化学偏好方面存在差异之外，我们还提供了证据表明这些酶在其底物的北/南构象偏好以及缺乏 O(4') 氧对碳环底物酶促脱氨动力学的影响程度。本研究中使用的碳环核苷底物具有柔性环戊烷环或刚性双环 [3.1.0] 己烷支架。
• Conformationally Restricted Nucleosides. The Reaction of Adenosine Deaminase with Substrates Built on a Bicyclo[3.1.0]hexane Template
  作者：Victor E. Marquez、Pamela Russ、Randolph Alonso、Maqbool A. Siddiqui、Kye-Jung Shin、Clifford George、Marc C. Nicklaus、Fang Dai、Harry Ford

  DOI：10.1080/15257779908041487

  日期：1999.4

  Adenosine deaminase (ADA) can discriminate between two distinct (North and South), conformationally rigid substrate conformers. (N)-methanocarba-2'dA (4) is deaminated 100 times faster than the antipodal (S)-methanocarba-2'dA (5), whereas a non-rigid analogue, aristeromycin (6), is deaminated at an intermediate rate. These results are in agreement with crystallographic data from ADA-ribonucleoside complexes showing the furanose ring of the bound purine in a C3'-endo (North) conformation. The data presented here suggests that 4 and 5 are useful probes to ascertain conformational preferences by purine metabolizing enzymes.
• Synthesis of Conformationally Restricted Carbocyclic Nucleosides: The Role of the O(4′)-Atom in the Key Hydration Step of Adenosine Deaminase
  作者：Victor E. Marquez、Pamela Russ、Randolph Alonso、Maqbool A. Siddiqui、Susana Hernandez、Clifford George、Marc C. Nicklaus、Fang Dai、Harry Ford, Jr.

  DOI：10.1002/(sici)1522-2675(19991215)82:12<2119::aid-hlca2119>3.0.co;2-y

  日期：1999.12.15