4'-Ethynyl-4'-thio-2'-deoxyadenosine | 1320269-94-0

• 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: 4'-Ethynyl-4'-thio-2'-deoxyadenosine
• 英文别名: (2R,3S,5R)-5-(6-aminopurin-9-yl)-2-ethynyl-2-(hydroxymethyl)thiolan-3-ol
• CAS: 1320269-94-0
• 化学式: C₁₂H₁₃N₅O₂S
• 分子量: 291.334
• InChiKey: UJXHMQHTBRBLIZ-JOAULVNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1,4-anhydro-5-O-(t-butyldimethylsilyloxymethyl)-4-C-formyl-2,3-O-isopropylidene-4-thio-D-ribitol 在 咪唑 、 N-碘代丁二酰亚胺 、 三乙基硼 、 四丁基氟化铵 、 氧气 、 三正丁基氢锡 、 potassium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 正戊烷 为溶剂， 反应 141.5h， 生成 4'-Ethynyl-4'-thio-2'-deoxyadenosine
  参考文献：
  名称：

  Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI

  摘要：

  The synthesis of 4'-ethynyl-2'-deoxy-4'-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal 16 served as a glycosyl donor. Electrophilic glycosidation between 16 and the silylated nucleobases (N-4-acetylcytosine, N-6-benzoyladenine, and N-2-acetyl-O-6-diphenylcarbamoylguanine) was carried out in the presence of N-iodosuccinimide (NIS), leading to the exclusive formation of the desired beta-anomers 29, 33, and 36. Anti-HIV studies demonstrated that these 4'-thio nucleosides were less cytotoxic to T-lymphocyte (i.e., MT-4 cells) than the corresponding 4'-ethynyl derivatives of 2'-deoxycytidine (44), 2'-deoxyadenosine (45), and 2'-deoxyguanosine (46). Comparison of the selectivity indices (SI) was made between 4'-thionucleosides (32, 41, and 43) and the corresponding 4'-oxygen analogues 44-46 by using the reported CC50 and EC50 values. In the case of cytosine and adenine nucleosides, comparable SI values were obtained as follows: 32 (545) and 44 (458); 41 (>230) and 45 (1630). In contrast, 4'-ethynyl-2'-deoxy-4'-thioguanosine 43 was found to possess a SI value of >18200, which is 20 times better than that of 46 (933).

  DOI：

  10.1021/ml2001054

文献信息

• Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI
  作者：Kazuhiro Haraguchi、Hisashi Shimada、Keigo Kimura、Genta Akutsu、Hiromichi Tanaka、Hiroshi Abe、Takayuki Hamasaki、Masanori Baba、Elizabeth A. Gullen、Ginger E. Dutschman、Yung-Chi Cheng、Jan Balzarini

  DOI：10.1021/ml2001054

  日期：2011.9.8

  The synthesis of 4'-ethynyl-2'-deoxy-4'-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal 16 served as a glycosyl donor. Electrophilic glycosidation between 16 and the silylated nucleobases (N-4-acetylcytosine, N-6-benzoyladenine, and N-2-acetyl-O-6-diphenylcarbamoylguanine) was carried out in the presence of N-iodosuccinimide (NIS), leading to the exclusive formation of the desired beta-anomers 29, 33, and 36. Anti-HIV studies demonstrated that these 4'-thio nucleosides were less cytotoxic to T-lymphocyte (i.e., MT-4 cells) than the corresponding 4'-ethynyl derivatives of 2'-deoxycytidine (44), 2'-deoxyadenosine (45), and 2'-deoxyguanosine (46). Comparison of the selectivity indices (SI) was made between 4'-thionucleosides (32, 41, and 43) and the corresponding 4'-oxygen analogues 44-46 by using the reported CC50 and EC50 values. In the case of cytosine and adenine nucleosides, comparable SI values were obtained as follows: 32 (545) and 44 (458); 41 (>230) and 45 (1630). In contrast, 4'-ethynyl-2'-deoxy-4'-thioguanosine 43 was found to possess a SI value of >18200, which is 20 times better than that of 46 (933).