5'-(N-L-leucylsulfonamido)-5'-deoxyadenosine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-(N-L-leucylsulfonamido)-5'-deoxyadenosine
• 英文别名: (2S)-2-amino-N-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfonyl]-4-methylpentanamide
• 化学式: C₁₆H₂₅N₇O₆S
• 分子量: 443.484
• InChiKey: BMSAWSHPLFPIJE-LEJQEAHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  217
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5’-deoxy-2’,3’-O-isopropylidene-5’-thioladenosine 在 ammonium hydroxide 、 1,3-二氯-5,5-二甲基海因 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.08h， 生成 5'-(N-L-leucylsulfonamido)-5'-deoxyadenosine
  参考文献：
  名称：

  5′-(N-aminoacyl)-sulfonamido-5′-deoxyadenosine: Attempts for a stable alternative for aminoacyl-sulfamoyl adenosines as aaRS inhibitors

  摘要：

  Synthesis of aminoacyl-sulfamoyl adenosines (aaSAs) and their peptidyl conjugates as aminoacyl tRNA synthetase (aaRS) inhibitors remains problematic due to the low yield of the aminoacylation and the subsequent conjugation reaction causing concomitant formation of a cyclic adenosine derivative. In an effort to reduce this undesirable side reaction, we aimed to prepare the corresponding aminoacyl sulfonamide (aaSoA) analogues as more stable alternatives for aaSA derivatives. Deletion of the 5'-oxygen in aaSA analogues should render the C-5' less electrophilic and therefore improve the stability of the aminoacyl sulfamate analogues. We therefore synthesized six sulfonamides and compared their activity against the respective aaSA analogues. However, except for the aspartyl derivative, the new compounds are not able to inhibit the corresponding aaRS. Possible reasons for this loss of activity are discussed by modeling and comparison of the newly synthesized aaSoA derivatives with their parent aaSA analogues. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.02.010

文献信息

• 5′-(N-aminoacyl)-sulfonamido-5′-deoxyadenosine: Attempts for a stable alternative for aminoacyl-sulfamoyl adenosines as aaRS inhibitors
  作者：Bharat Gadakh、Simon Smaers、Jef Rozenski、Mathy Froeyen、Arthur Van Aerschot

  DOI：10.1016/j.ejmech.2015.02.010

  日期：2015.3

  Synthesis of aminoacyl-sulfamoyl adenosines (aaSAs) and their peptidyl conjugates as aminoacyl tRNA synthetase (aaRS) inhibitors remains problematic due to the low yield of the aminoacylation and the subsequent conjugation reaction causing concomitant formation of a cyclic adenosine derivative. In an effort to reduce this undesirable side reaction, we aimed to prepare the corresponding aminoacyl sulfonamide (aaSoA) analogues as more stable alternatives for aaSA derivatives. Deletion of the 5'-oxygen in aaSA analogues should render the C-5' less electrophilic and therefore improve the stability of the aminoacyl sulfamate analogues. We therefore synthesized six sulfonamides and compared their activity against the respective aaSA analogues. However, except for the aspartyl derivative, the new compounds are not able to inhibit the corresponding aaRS. Possible reasons for this loss of activity are discussed by modeling and comparison of the newly synthesized aaSoA derivatives with their parent aaSA analogues. (C) 2015 Elsevier Masson SAS. All rights reserved.