(2R,3S,5R)-5-(6-氨基嘌呤-9-基)-2-(羟基甲基)-4-亚甲基四氢呋喃-3-醇 | 104409-41-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: (2R,3S,5R)-5-(6-氨基嘌呤-9-基)-2-(羟基甲基)-4-亚甲基四氢呋喃-3-醇
• 中文别名: 2'-脱氧-2'-亚甲基腺苷
• 英文名称: 2'-deoxy-2'-methyleneadenosine
• 英文别名: (2R,3S,5R)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-4-methylideneoxolan-3-ol
• CAS: 104409-41-8
• 化学式: C₁₁H₁₃N₅O₃
• 分子量: 263.256
• InChiKey: JGQTWRGPSIKPOT-CDOJRTKCSA-N

物化性质

• 沸点：
  617.5±65.0 °C(Predicted)
• 密度：
  1.80±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R,3S,5R)-5-(6-氨基嘌呤-9-基)-2-(羟基甲基)-4-亚甲基四氢呋喃-3-醇 在 吡啶 、 咪唑 、 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 95.0h， 生成 6-N,N-dibenzoyl-9-(3-O-(tert-butyldimethylsilyl)-2,5-dideoxy-5-iodo-2-methylene-β-D-erythro-pentofuranosyl)adenine
  参考文献：
  名称：

  Nucleic acid related compounds. 70. Synthesis of 2'(and 3')-deoxy-2'(and 3')-methyleneadenosines and bis(methylene)furan 4',5'-didehydro-5'-deoxy-2'(and 3')-methyleneadenosines. Inhibitors of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase

  摘要：

  Wittig treatment of 3',5'(or 2',5')-bis-O-silyl-2'(or 3')-ketoadenosine derivatives with methylenetriphenylphosphorane and deprotection gave the 2'(or 3')-deoxy-2'(or 3')-methyleneadenosines, respectively. Enzymatic deamination afforded the 2'(or 3')-deoxy-2'(or 3')-methyleneinosines. Treatment of 2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-methylene-5'-O-tosyladenosine (14) with sodium 2-methyl-2-butoxide and deprotection gave 9-(3,5-dideoxy-3-methylene-beta-D-glycero-pent-4-enofuranosyl)adenine (20). Analogous treatment of a protected 2',5'-dideoxy-5'-iodo-2'-methyleneadenosine derivative gave 9-(2,5-dideoxy-2-methylene-beta-D-glycero-pent-4-enofuranosyl)adenine (22). Biochemical aspects of the putative mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase by these compounds are discussed.

  DOI：

  10.1021/jo00025a029
• 作为产物：
  描述：

  9-(3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuran-2-ulosyl)adenine 在 四丁基氟化铵 、 sodium tert-pentoxide 作用下， 以 四氢呋喃 为溶剂， 反应 54.0h， 生成 (2R,3S,5R)-5-(6-氨基嘌呤-9-基)-2-(羟基甲基)-4-亚甲基四氢呋喃-3-醇
  参考文献：
  名称：

  Nucleic acid related compounds. 70. Synthesis of 2'(and 3')-deoxy-2'(and 3')-methyleneadenosines and bis(methylene)furan 4',5'-didehydro-5'-deoxy-2'(and 3')-methyleneadenosines. Inhibitors of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase

  摘要：

  Wittig treatment of 3',5'(or 2',5')-bis-O-silyl-2'(or 3')-ketoadenosine derivatives with methylenetriphenylphosphorane and deprotection gave the 2'(or 3')-deoxy-2'(or 3')-methyleneadenosines, respectively. Enzymatic deamination afforded the 2'(or 3')-deoxy-2'(or 3')-methyleneinosines. Treatment of 2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-methylene-5'-O-tosyladenosine (14) with sodium 2-methyl-2-butoxide and deprotection gave 9-(3,5-dideoxy-3-methylene-beta-D-glycero-pent-4-enofuranosyl)adenine (20). Analogous treatment of a protected 2',5'-dideoxy-5'-iodo-2'-methyleneadenosine derivative gave 9-(2,5-dideoxy-2-methylene-beta-D-glycero-pent-4-enofuranosyl)adenine (22). Biochemical aspects of the putative mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase by these compounds are discussed.

  DOI：

  10.1021/jo00025a029

文献信息

• Nucleosides and nucleotides. LXV Synthesis of 8,2'-methano- and 8,2'-ethanoadenosines.
  作者：HIROYUKI USUI、TOHRU UEDA

  DOI：10.1248/cpb.34.1518

  日期：——

  Treatment of 3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl)-2'-ketoadenosine (1) with methylenetriphenylphosphorane gave the 2'-methylene derivative (2). Hydroxylation of 1 with OsO4 gave the 2'-hydroxymethyladenosine (4), which was then converted to the 2'-phenylthiomethyl derivative (5). Photocyclization followed by deprotection of the product furnished 8, 2'-methanoadenosine (7), and adenosine fixed in a high-anti conformation. Oxidation of a 2'-hydroxyethylideneadenosine with OsO4 gave the 2'-dihydroxyethyladenosine (10), which was also converted to the 2'-(2-phenylthioethyl) derivative (11). The photocyclization of 11 and successive elimination of the hydroxyl group gave the 8, 2'-ethenoadenosine (13). Catalytic hydrogenation and deprotection of 13 afforded 8, 2'-ethanoadenosine (15). The circular dichroism spectral features of C-cycloadenosine are discussed.

  将 3'，5'-O-(四异丙基二硅氧烷-1，3-二基)-2'-酮腺苷 (1) 与亚甲基三苯基膦处理，可得到 2'-亚甲基衍生物 (2)。用 OsO4 对 1 进行羟基化反应，得到 2'- 羟甲基腺苷 (4)，然后将其转化为 2'- 苯硫甲基衍生物 (5)。对产物进行光环化和脱保护处理后，得到 8、2'-甲基腺苷（7）和以高反构象固定的腺苷。用 OsO4 氧化 2'-hydroxyethylideneadenosine 可以得到 2'-dihydroxyethyladenosine (10)，它还可以转化为 2'-(2-phenylthioethyl) 衍生物 (11)。11 的光环化和羟基的连续消除得到了 8,2'-乙烯腺苷（13）。对 13 进行催化氢化和脱保护处理后，得到了 8，2'-乙烯腺苷（15）。本文讨论了 C-胞二色谱的光谱特征。
• Nucleic acid related compounds. 77. 2′,3′-Didehydro-2′,3′-dideoxy-2′(and 3′)-methylnucleosides via [3,3]-sigmatropic rearrangements of 2′(and 3′)-methylene-3′(and 2′)-<i>O</i>-thiocarbonyl derivatives and radical reduction of a 2′-chloro-3′-methylene analogue
  作者：Vincente Samano、Morris J. Robins

  DOI：10.1139/v93-027

  日期：1993.2.1

  Treatment of 5′-O-(tert-butyldiphenylsilyl)-2′(and 3′)-deoxy-2′(and 3′)-methyleneuridine (and adenosine) derivatives with phenyl chlorothionocarbonate gave the 3′(and 2′)-O-phenoxythiocarbonyl intermediates, which underwent spontaneous [3,3]-sigmatropic rearrangement to give the 2′,3′-didehydro-2′,3′-dideoxy-2′(and 3′)-(phenoxycarbonylthio)methyl analogues. These allylic thioesters were subjected to tributylstannane-mediated hydrodesulfurization and deprotection to give 2′,3′-didehydro-2′,3′-dideoxy-2′(and 3′)-methyluridine (and adenosine). Tributylstannane-mediated hydrodehalogenation of a 2′-chloro-2′,3′-dideoxy-3′-methyleneuridine derivative afforded the 2′,3′-didehydro-2′,3′-dideoxy-3′-methyl product of allylic transposition exclusively.

  对5'-O-(叔丁基二苯基硅基)-2'（和3'）-去氧-2'（和3'）-亚甲基尿苷（和腺苷）衍生物进行苯基氯硫代碳酸酯处理，得到3'（和2'）-O-苯氧硫酰中间体，这些中间体经历自发的[3,3]-sigmatropic重排反应，产生2'，3'-二去氢-2'，3'-二去氧-2'（和3'）-（苯氧羰基硫）甲基类似物。这些烯丙基硫酯经过三丁基锡介导的脱硫化和去保护作用，得到2'，3'-二去氢-2'，3'-二去氧-2'（和3'）-甲基尿苷（和腺苷）。对2'-氯-2'，3'-二去氧-3'-亚甲基尿苷衍生物进行三丁基锡介导的脱卤化反应，仅得到烯丙基转位的2'，3'-二去氢-2'，3'-二去氧-3'-甲基产物。
• Changing Fates of the Substrate Radicals Generated in the Active Sites of the B₁₂-Dependent Radical SAM Enzymes OxsB and AlsB
  作者：Yu-Hsuan Lee、Yu-Cheng Yeh、Po-Hsun Fan、Aoshu Zhong、Mark W. Ruszczycky、Hung-wen Liu

  DOI：10.1021/jacs.2c12953

  日期：2023.2.15

  in a similar reaction during the biosynthesis of albucidin. Herein, OxsB and AlsB are shown to also catalyze radical mediated, stereoselective C2′-methylation of 2′-deoxyadenosine monophosphate. This reaction proceeds with inversion of configuration such that the resulting product also possesses a C2′ hydrogen atom available for abstraction. However, in contrast to methylation, subsequent rounds of

  OxsB 是 B 12-依赖性自由基 SAM 酶，催化 2'-脱氧腺苷 5'-磷酸氧化环收缩为脱氢的、含氧杂环丁烷的氧杂环辛 A 磷酸前体。AlsB 是 OxsB 的同源物，在白布西定的生物合成过程中参与类似的反应。在此，OxsB 和 AlsB 也显示出催化自由基介导的立体选择性 2'-脱氧腺苷一磷酸的 C2'-甲基化。该反应随着构型的反转进行，使得所得产物也具有可用于提取的 C2' 氢原子。然而，与甲基化相反，后续轮次的催化导致新添加的甲基的 C-C 脱氢产生 2'-亚甲基，然后自由基加成 5'-脱氧腺苷部分产生异二聚体。12依赖自由基 SAM 酶并强调自由基中间体对沿不同反应途径分叉的敏感性，即使在酶的高度组织化活性位点内也是如此。
• CYCLIC NUCLEOTIDE DERIVATIVE
  申请人：NIPPON SHINYAKU COMPANY, LIMITED

  公开号：EP0753525A1

  公开（公告）日：1997-01-15

  The object of the present invention is to provide useful cyclic nucleotide derivatives, for example, as an antidementia drug, an antiarrhythmic drug, a therapeutic drug for bronchial asthma or an antiinflammatory agent. The invention relates to cyclic nucleotide derivatives of the following general formula [I] and the pharmaceutically acceptable salts thereof. wherein R1 represents hydroxy, amino, or -NR11R12 in which R11 and R12 may be the same or different and each represents alkyl; R2 represents hydrogen, amino, or hydroxy; R3 represents hydrogen, halogen, alkyl, hydroxy or mercapto; R4 represents hydrogen, hydroxy, acyloxy or alkoxy; R5 represents alkyl or aryl; R6 represents hydrogen, halogen or alkyl.

  本发明的目的是提供有用的环核苷酸衍生物，例如作为抗痴呆药物、抗心律失常药物、支气管哮喘治疗药物或抗炎剂。 本发明涉及以下通式[I]的环核苷酸衍生物及其药学上可接受的盐类。 其中R1代表羟基、氨基或-NR11R12，其中R11和R12可以相同或不同，各自代表烷基；R2代表氢、氨基或羟基；R3代表氢、卤素、烷基、羟基或巯基；R4代表氢、羟基、酰氧基或烷氧基；R5代表烷基或芳基；R6代表氢、卤素或烷基。
• Nucleic acid related compounds. 70. Synthesis of 2'(and 3')-deoxy-2'(and 3')-methyleneadenosines and bis(methylene)furan 4',5'-didehydro-5'-deoxy-2'(and 3')-methyleneadenosines. Inhibitors of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase
  作者：Vicente Samano、Morris J. Robins

  DOI：10.1021/jo00025a029

  日期：1991.12

  Wittig treatment of 3',5'(or 2',5')-bis-O-silyl-2'(or 3')-ketoadenosine derivatives with methylenetriphenylphosphorane and deprotection gave the 2'(or 3')-deoxy-2'(or 3')-methyleneadenosines, respectively. Enzymatic deamination afforded the 2'(or 3')-deoxy-2'(or 3')-methyleneinosines. Treatment of 2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-methylene-5'-O-tosyladenosine (14) with sodium 2-methyl-2-butoxide and deprotection gave 9-(3,5-dideoxy-3-methylene-beta-D-glycero-pent-4-enofuranosyl)adenine (20). Analogous treatment of a protected 2',5'-dideoxy-5'-iodo-2'-methyleneadenosine derivative gave 9-(2,5-dideoxy-2-methylene-beta-D-glycero-pent-4-enofuranosyl)adenine (22). Biochemical aspects of the putative mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase by these compounds are discussed.