(2R,3R,5S)-2-(6-amino-9H-purin-9-yl)-5-(chloromethyl)tetrahydrofuran-3-ol | 57274-15-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (2R,3R,5S)-2-(6-amino-9H-purin-9-yl)-5-(chloromethyl)tetrahydrofuran-3-ol
• 英文别名: 5'-chloro-3',5'-dideoxyadenosine；5'-chloro-3'-deoxyadenosine；5'-chloro-3',5'-dideoxy-adenosine；2-(6-Amino-purin-9-yl)-5-chloromethyl-tetrahydro-furan-3-ol；(2R,3R,5S)-2-(6-aminopurin-9-yl)-5-(chloromethyl)oxolan-3-ol
• CAS: 57274-15-4
• 化学式: C₁₀H₁₂ClN₅O₂
• 分子量: 269.691
• InChiKey: SUVZONMRUXNRHL-BAJZRUMYSA-N

物化性质

• 沸点：
  598.7±60.0 °C(Predicted)
• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3R,5S)-2-(6-amino-9H-purin-9-yl)-5-(chloromethyl)tetrahydrofuran-3-ol 在 sodium hydride 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 2'-O-acetyl-3'-deoxy-5'-S-(4-methoxyphenyl)-5'-thioadenosine
  参考文献：
  名称：

  Nucleic Acid Related Compounds. 101. S-Adenosyl-l-homocysteine Hydrolase Does Not Hydrate (5‘-Fluoro)vinyl or (6‘-Halo)homovinyl Analogues Derived from 3‘-Deoxyadenosine or 3‘-(Chloro or Fluoro)-3‘-deoxyadenosine¹

  摘要：

  S-Adenosyl-L-homocysteine (AdoHcy) hydrolase is crucial for the maintenance of biomethylation. The usual mechanistic sequence involves oxidation of AdoHcy at C3' followed by elimination of L-homocysteine, Michael addition of water, and reduction to give adenosine. A 6'-fluorohomovinyladenosine analogue (EDDFHA) undergoes hydration of the 5',6' double bond (hydrolytic activity) at a more rapid rate than oxidation at C3'. Three 4',5'-didehydro-5'-deoxy-5'-fluoro nucleoside analogues were prepared from 3'-deoxy- and 3'-(chloro and fluoro)-3'-deoxyadenosine via generation of the vinyl fluorides by thermolysis of 5'-fluoro-5'-thioether sulfoxides. The 3'-deoxy analogues of 6'-halohomovinyladenosines were prepared by Wittig extension with a 3'-deoxy-5'-carboxaldehyde and halodestannylation of vinyl stannanes. The 3'-hydroxyl group appears to be essential for binding to AdoHcy hydrolase. No hydrolytic activity at C5' or C6' was observed with the nonoxidizable 3'-deoxy or 3'-(chloro or fluoro) analogues in contrast with their 3'-hydroxy counterparts (ZDDFA and EDDFHA). These 3'-modified analogues cannot reduce enzyme-bound NAD(+) to NADH and do not produce time-dependent inhibition of AdoHcy hydrolase, but are weak competitive inhibitors (K-i = 150-200 mu M).

  DOI：

  10.1021/jo971741u
• 作为产物：
  描述：

  虫草素 在 吡啶 、 氯化亚砜 作用下， 以 乙腈 为溶剂， 反应 19.0h， 以61%的产率得到(2R,3R,5S)-2-(6-amino-9H-purin-9-yl)-5-(chloromethyl)tetrahydrofuran-3-ol
  参考文献：
  名称：

  S-腺苷甲硫氨酸辅因子修饰增强小分子C-烷基化的生物催化库。

  摘要：

  描述了通过原位形成S-腺苷甲硫氨酸（SAM）辅助因子类似物来增强小分子C-烷基化范围的串联酶促策略。SAM形成酶SalL中存在的溶剂暴露通道可耐受在腺嘌呤核苷碱基2位修饰的5'-氯-5'-脱氧腺苷（ClDA）类似物。SalL催化的辅因子生产与甲基转移酶（MTase）催化的C-（间）乙基转移至香豆素底物相结合，相对于使用缺乏核碱基修饰的辅因子获得的C-（间）乙基香豆素具有更高的收率和更大的底物范围。建立影响C-烷基化的分子决定簇为开发用于制备高价值小分子的后期酶促平台提供了基础。

  DOI：

  10.1002/anie.201908681

文献信息

• Experimental Study of Hydrogen Bonding Potentially Stabilizing the 5′-Deoxyadenosyl Radical from Coenzyme B₁₂
  作者：Peter Friedrich、Ulrich Baisch、Ross W. Harrington、Fredrick Lyatuu、Kai Zhou、Felix Zelder、William McFarlane、Wolfgang Buckel、Bernard T. Golding

  DOI：10.1002/chem.201201840

  日期：2012.12.7

  Coenzyme B12 can assist radical enzymes that accomplish the vicinal interchange of a hydrogen atom with a functional group. It has been proposed that the CoC bond homolysis of coenzyme B12 to cob(II)alamin and the 5′‐deoxyadenosyl radical is aided by hydrogen bonding of the corrin C19H to the 3′‐O of the ribose moiety of the incipient 5′‐deoxyadenosyl radical, which is stabilized by 30 kJ mol−1 (B

  辅酶B 12可以协助自由基酶完成氢原子与官能团的邻近交换。已经提出的是，钴辅酶B的C键均裂12至穗轴（II）胺素和5'-脱氧腺苷基团是通过氢键咕啉C19辅助 H至的核糖部分的3'-O-初期5'-脱氧腺苷基团，其通过为30kJ摩尔稳定-1（B. Durbeej等人，化学式欧洲药典J. 2009，15，8578-8585）。非对映异构体（R）-和（S）-2,3-二羟丙基钴胺素用作辅酶B 12的模型。用于C19的NMR信号的低磁场移位观察ħ质子的（- [R ）-异构体（δ = 4.45对4.01 ppm的对于（小号） -异构体），并且可以归因于C19之间的分子内氢键 H和CHOH的氧。的晶体结构（- [R ）-和（小号）-2,3- dihydroxypropylcobalamin表明C19 的3.214H⋅⋅⋅O距离（7）（- [R异构体）和3.281（11）A（小号-异构体），其建议弱氢键相互作用（-Δ
• Novel Trypanocidal Analogs of 5′-(Methylthio)-Adenosine
  作者：Janice R. Sufrin、Arthur J. Spiess、Canio J. Marasco、Donna Rattendi、Cyrus J. Bacchi

  DOI：10.1128/aac.00480-07

  日期：2008.1

  The purine nucleoside 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) is an analog of the polyamine pathway metabolite 5'-deoxy-5'-(methylthio)-adenosine (MTA). HETA is a lead structure for the ongoing development of selectively targeted trypanocidal agents. Thirteen novel HETA analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of Trypanosoma

  嘌呤核苷 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) 是多胺途径代谢物 5'-deoxy-5'-(methylthio)-adenosine (MTA) 的类似物。HETA 是正在进行的选择性靶向锥虫杀灭剂开发的先导结构。合成了 13 种新型 HETA 类似物，并检查了它们对血流形式的布氏布氏锥虫 LAB 110 EATRO 和至少一种耐药性布氏锥虫临床分离株的体外锥虫杀灭活性。还在无细胞试验中评估了新化合物作为锥虫 MTA 磷酸化酶底物的活性。该组中最有效的类似物是 5'-deoxy-5'-(羟乙硫基)-tubercidin，其体外细胞毒性（50% 抑制浓度 [IC50]，10 nM）是 HETA 的 45 倍（IC50，450 nM) 对抗喷他脒抗性临床分离株 KETRI 269。结构-活性分析表明，锥虫 MTA 磷酸化酶对 HETA
• <i>S</i> ‐Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule <i>C</i> ‐Alkylation
  作者：Iain J. W. McKean、Joanna C. Sadler、Anibal Cuetos、Amina Frese、Luke D. Humphreys、Gideon Grogan、Paul A. Hoskisson、Glenn A. Burley

  DOI：10.1002/anie.201908681

  日期：2019.12.2

  A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5'-chloro-5'-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl

  描述了通过原位形成S-腺苷甲硫氨酸（SAM）辅助因子类似物来增强小分子C-烷基化范围的串联酶促策略。SAM形成酶SalL中存在的溶剂暴露通道可耐受在腺嘌呤核苷碱基2位修饰的5'-氯-5'-脱氧腺苷（ClDA）类似物。SalL催化的辅因子生产与甲基转移酶（MTase）催化的C-（间）乙基转移至香豆素底物相结合，相对于使用缺乏核碱基修饰的辅因子获得的C-（间）乙基香豆素具有更高的收率和更大的底物范围。建立影响C-烷基化的分子决定簇为开发用于制备高价值小分子的后期酶促平台提供了基础。
• Nucleic Acid Related Compounds. 101. <i>S</i>-Adenosyl-<scp>l</scp>-homocysteine Hydrolase Does Not Hydrate (5‘-Fluoro)vinyl or (6‘-Halo)homovinyl Analogues Derived from 3‘-Deoxyadenosine or 3‘-(Chloro or Fluoro)-3‘-deoxyadenosine¹
  作者：Morris J. Robins、Vladimir Neschadimenko、Bong-Oh Ro、Chong-Sheng Yuan、Ronald T. Borchardt、Stanislaw F. Wnuk

  DOI：10.1021/jo971741u

  日期：1998.2.1

  S-Adenosyl-L-homocysteine (AdoHcy) hydrolase is crucial for the maintenance of biomethylation. The usual mechanistic sequence involves oxidation of AdoHcy at C3' followed by elimination of L-homocysteine, Michael addition of water, and reduction to give adenosine. A 6'-fluorohomovinyladenosine analogue (EDDFHA) undergoes hydration of the 5',6' double bond (hydrolytic activity) at a more rapid rate than oxidation at C3'. Three 4',5'-didehydro-5'-deoxy-5'-fluoro nucleoside analogues were prepared from 3'-deoxy- and 3'-(chloro and fluoro)-3'-deoxyadenosine via generation of the vinyl fluorides by thermolysis of 5'-fluoro-5'-thioether sulfoxides. The 3'-deoxy analogues of 6'-halohomovinyladenosines were prepared by Wittig extension with a 3'-deoxy-5'-carboxaldehyde and halodestannylation of vinyl stannanes. The 3'-hydroxyl group appears to be essential for binding to AdoHcy hydrolase. No hydrolytic activity at C5' or C6' was observed with the nonoxidizable 3'-deoxy or 3'-(chloro or fluoro) analogues in contrast with their 3'-hydroxy counterparts (ZDDFA and EDDFHA). These 3'-modified analogues cannot reduce enzyme-bound NAD(+) to NADH and do not produce time-dependent inhibition of AdoHcy hydrolase, but are weak competitive inhibitors (K-i = 150-200 mu M).