3'-deoxy-3'-fluoro-5'-S-(4-methoxyphenyl)-5'-thioadenosine | 203584-05-8

• 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: 3'-deoxy-3'-fluoro-5'-S-(4-methoxyphenyl)-5'-thioadenosine
• 英文别名: (2R,3S,4S,5S)-2-(6-aminopurin-9-yl)-4-fluoro-5-[(4-methoxyphenyl)sulfanylmethyl]oxolan-3-ol
• CAS: 203584-05-8
• 化学式: C₁₇H₁₈FN₅O₃S
• 分子量: 391.426
• InChiKey: OGFMKQXWWZTSKC-CTWCOEIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3'-deoxy-3'-fluoro-5'-S-(4-methoxyphenyl)-5'-thioadenosine 在 间氯过氧苯甲酸 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 7.58h， 生成
  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：

  2',3',5'-tri-O-acetyl adenosine 在 氯化亚砜 、 氨 、 sodium hydride 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 甲醇 、 六甲基磷酰三胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 3'-deoxy-3'-fluoro-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

文献信息

• 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).