1-[2-deoxy-4-C-ethynyl-4-thio-β-D-ribofuranosyl]cytosine | 1206885-92-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-[2-deoxy-4-C-ethynyl-4-thio-β-D-ribofuranosyl]cytosine
• 英文别名: 4-amino-1-[(2R,4S,5R)-5-ethynyl-4-hydroxy-5-(hydroxymethyl)thiolan-2-yl]pyrimidin-2-one
• CAS: 1206885-92-8
• 化学式: C₁₁H₁₃N₃O₃S
• 分子量: 267.309
• InChiKey: WVHCIPOULMRSKI-JVUFJMBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  4

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 130.5h， 生成 1-[2-deoxy-4-C-ethynyl-4-thio-β-D-ribofuranosyl]cytosine
  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′-substituted 2′-deoxy-4′-thiocytidines and its evaluation for antineoplastic and antiviral activities
  作者：Kazuhiro Haraguchi、Hiroki Kumamoto、Kiju Konno、Hideki Yagi、Yutaka Tatano、Yuki Odanaka、Satoko Shimbara Matsubayashi、Robert Snoeck、Graciela Andrei

  DOI：10.1016/j.tet.2019.06.044

  日期：2019.8

  glycosidation utilizing 36 and 43 for the synthesis of 37 and 44. Introduction of the azido group was carried out by nucleophilic substitution in the 4′-benzoyloxy derivative 22a. On the other hand, 9 and 10 were synthesized by way of the chemical manipulation of the hydroxymethyl group at the 4′-position of 46. Evaluation of the antineoplastic activity of 2 and 7–10 against human B-cell (CCRF-SB) and

  4′-叠氮基-（7），4′- C-氟甲基-（8 ），4′- C-乙炔基-（9）和4′- C-氰基-（10）2′-脱氧-4′-硫胞苷具有已合成。在这项研究中，发现利用路易斯酸促进的Vorbrüggen型糖苷化反应中利用12分离的4'-硫尿嘧啶核苷13的产率要高于甲硅烷基化尿嘧啶和11之间的亲电糖苷化反应的产率。这一改进的结果促使我们用36和43进行糖苷化以合成37和44。叠氮基的引入是通过在4'-苯甲酰氧基衍生物22a中的亲核取代进行的。另一方面，通过化学操作46的4'-位上的羟甲基合成了9和10。 对2和7-10对人B细胞（CCRF-SB）和T细胞白血病（Molt-4）细胞的抗肿瘤活性的评估表明，4'-叠氮基（7）和4'- C-氟甲基-（8）衍生物表现出细胞毒性活性，而在4'- C-乙炔基-（9）和4'- C-氰基-（10）衍生物以及母体化合物2中未观察到细胞毒性。具有对VZV和HSV-1
• 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).