(1R,2S,4S,5S)-1-hydroxymethyl-2-hydroxy-4-(6-amino-9-purinyl)bicyclo<3.1.0>hexane | 169191-08-6

• 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: (1R,2S,4S,5S)-1-hydroxymethyl-2-hydroxy-4-(6-amino-9-purinyl)bicyclo<3.1.0>hexane
• 英文别名: (1R,2S,4S,5S)-4-(6-Amino-9H-purin-9-yl)-2-hydroxybicyclo[3.1.0]hexan-1-methanol；(N)-methanocarba-2'-deoxyadenosine；North-dAdo；(1S,2S,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)bicyclo[3.1.0]hexan-4-ol；(1R,2S,4S,5S)-4-(6-aminopurin-9-yl)-1-(hydroxymethyl)bicyclo[3.1.0]hexan-2-ol
• CAS: 169191-08-6
• 化学式: C₁₂H₁₅N₅O₂
• 分子量: 261.283
• InChiKey: GJDYOCPKYJVOMS-VXDIOVFMSA-N

物化性质

• 沸点：
  577.4±60.0 °C(Predicted)
• 密度：
  1.95±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 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：
  110
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2S,4S,5S)-1-hydroxymethyl-2-hydroxy-4-(6-amino-9-purinyl)bicyclo<3.1.0>hexane 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.25h， 生成 (1R,2S,4S,5S)-1-[(dibenzylphosphato)methyl]-4-(6-methylaminopurin-9-yl)bicyclo[3.1.0]hexane-2-(dibenzyl phosphate)
  参考文献：
  名称：

  核糖修饰的脱氧腺苷二磷酸类似物作为 P2Y(1) 受体配体的合成、生物活性和分子建模。

  摘要：

  已经探索了腺苷 3', 5'-二磷酸作为 P2Y(1) 受体拮抗剂的构效关系，揭示了 N(6)-甲基基团的效力增强作用和取代核糖部分的能力。 Nandanan et al. J. Med. Chem. 1999, 42, 1625-1638)。我们引入了受约束的碳环（以探索糖褶皱的作用）、与腺嘌呤部分的非糖基键以及磷酸基团移位。每种类似物对 P2Y(1) 受体的生物学活性的特点是测量其刺激火鸡红细胞膜中的磷脂酶 C（激动剂作用）和抑制其由 30 nM 2-甲基硫腺苷-5'-二磷酸（拮抗剂作用）引起的刺激的能力）。N(6)-甲基在几个案例中的加入将纯激动剂转化为拮抗剂。碳环 N(6)-methyl-2'-deoxyadenosine bisphosphate 类似物是纯 P2Y(1) 受体拮抗剂，与核糖类似物 (MRS 2179) 等效。在一系列环约束的甲卡巴衍生物中，稠合环丙烷部分将核苷的假糖环约束为北

  DOI：

  10.1021/jm990249v
• 作为产物：
  描述：

  (1S,2R)-1-benzyloxy-2-benzyloxymethylcyclopent-3-ene 在 palladium on activated charcoal 氢氧化钾 、 sodium periodate 、 甲酸 、 氨 、 diethylzinc 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 二甲基亚砜 、 苯 为溶剂， 反应 14.75h， 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：

  Synthesis of Conformationally Restricted Carbocyclic Nucleosides: The Role of the O(4′)-Atom in the Key Hydration Step of Adenosine Deaminase

  摘要：

  DOI：

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

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。
• Is the anomeric effect an important factor in the rate of adenosine deaminase catalyzed hydrolysis of purine nucleosides? A direct comparison of nucleoside analogues constructed on ribose and carbocyclic templates with equivalent heterocyclic bases selected to promote hydration
  作者：Susana Hernandez、Harry Ford、Victor E Marquez

  DOI：10.1016/s0968-0896(02)00099-8

  日期：2002.8

  [(N)-MCdA, (5)], a relatively weak substrate for adenosine deaminase (ADA)-relative rate of deamination ca. 100 times lower than adenosine-was modified with substitutions at positions 6 (6-fluoro, compound 6) and 8 (8-aza, compound 7) with the intent to improve the level of hydration and hence hydrolysis by ADA. In these substrates the fused cyclopropane moiety constrains the cyclopentane ring to mimic the

  （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，
• 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, Conformational Analysis, and Biological Activity of a Rigid Carbocyclic Analogue of 2′-Deoxy Aristeromycin Built on a Bicyclo[3.1.0]hexane Template
  作者：Maqbool A. Siddiqui、Harry Ford、Clifford George、Victor E. Marquez

  DOI：10.1080/07328319608002382

  日期：1996.1

  A new chiral synthesis of the pseudosugar synthon (1R,2S,4R,5S)-1-[(benzyloxy)methyl]-2-tert-butyloxy-4-hydroxybicyclo[3.1.0]hexane (12) is reported. This compound was used as a template for the construction of carbocyclic nucleoside 4, a conformationally rigid analogue of 2'-deoxyaristeromycin. The X-ray structure and H-1 NMR analysis confirmed the exclusive North [2'-exo ((2)E)] conformation of 4 which is vastly different from that of other non-rigid carbocyclic nucleosides. Compound 4 showed good in vitro antiviral activity against human cytomegalovirus and EBV with minimal cytotoxicity.
• A Remarkably Simple Chemicoenzymatic Approach to Structurally Complex Bicyclo[3.1.0]hexane Carbocyclic Nucleosides
  作者：Hyung R. Moon、Harry Ford、Victor E. Marquez

  DOI：10.1021/ol000238s

  日期：2000.11.1

  [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.