Benzoic acid (2R,3S,5R)-5-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester | 139433-04-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: Benzoic acid (2R,3S,5R)-5-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester
• 英文别名: [(2R,3S,5R)-5-[2-(2-methylpropanoylamino)-6-oxo-3H-purin-9-yl]-3-(methylsulfanylmethoxy)oxolan-2-yl]methyl benzoate
• CAS: 139433-04-8
• 化学式: C₂₃H₂₇N₅O₆S
• 分子量: 501.563
• InChiKey: VBRUWIKAOYFBIY-GVDBMIGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  35.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  137.43
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  Benzoic acid (2R,3S,5R)-5-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester 在 N-碘代丁二酰亚胺 、 molecular sieve 、 三氟甲磺酸三甲基硅酯 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 0.33h， 生成
  参考文献：
  名称：

  An Alternative Route to the Preparation of (3′ → 5′) Methylene Acetal Linked Di- and Trinucleosides

  摘要：

  脱氧核苷3′-O-(甲硫基甲基)乙缩醛1与碘代琥珀酰亚胺(NIS)和二丁基磷酸酯反应，生成相应的3′-O-(二丁氧基磷酰氧)甲基乙缩醛6。后者与适当保护的脱氧核苷受体3在三甲基硅基三氟甲磺酸盐(TMSOTf)的存在下缩合，通常得到(3′ → 5′)亚甲基乙缩醛连接的二聚体d(B1 ∧ B2) 4。此外，TMSOTf促进的供体6 (B1 = CBz)与3′-O-(甲硫基甲基)胸苷(8)的偶联反应生成二聚体9。9与NIS和二丁基磷酸酯反应生成二聚体10，成功用于与受体3(B2 = CBz和ABz)的TMSOTf辅助融合，得到相应的三聚体d(C∧T∧C) 11和d(C∧T∧A) 12。

  DOI：

  10.1055/s-1993-25915
• 作为产物：
  描述：

  二甲基硫 、 [(2R,3S,5R)-3-hydroxy-5-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]tetrahydrofuran-2-yl]methyl benzoate 在 2,6-二甲基吡啶 、 过氧化苯甲酰 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 以70%的产率得到Benzoic acid (2R,3S,5R)-5-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester
  参考文献：
  名称：

  An Alternative Route to the Preparation of (3′ → 5′) Methylene Acetal Linked Di- and Trinucleosides

  摘要：

  脱氧核苷3′-O-(甲硫基甲基)乙缩醛1与碘代琥珀酰亚胺(NIS)和二丁基磷酸酯反应，生成相应的3′-O-(二丁氧基磷酰氧)甲基乙缩醛6。后者与适当保护的脱氧核苷受体3在三甲基硅基三氟甲磺酸盐(TMSOTf)的存在下缩合，通常得到(3′ → 5′)亚甲基乙缩醛连接的二聚体d(B1 ∧ B2) 4。此外，TMSOTf促进的供体6 (B1 = CBz)与3′-O-(甲硫基甲基)胸苷(8)的偶联反应生成二聚体9。9与NIS和二丁基磷酸酯反应生成二聚体10，成功用于与受体3(B2 = CBz和ABz)的TMSOTf辅助融合，得到相应的三聚体d(C∧T∧C) 11和d(C∧T∧A) 12。

  DOI：

  10.1055/s-1993-25915

文献信息

• In Vitro and in Vivo Activities of Oligodeoxynucleotide-Based Thrombin Inhibitors Containing Neutral Formacetal Linkages
  作者：Gong-Xin He、John P. Williams、Michael J. Postich、S. Swaminathan、Regan G. Shea、Terry Terhorst、Veronica S. Law、Cheri T. Mao、Cathy Sueoka、Steven Coutré、Norbert Bischofberger

  DOI：10.1021/jm970766i

  日期：1998.10.1

  A series of 15-mer oligodeoxynucleotide analogues were synthesized, and their thrombin inhibitory activities in vitro and in vivo were evaluated. These oligodeoxynucleotide analogues share the same sequence (GGTTGGTGTGGTTGG) but have one or more phosphodiester linkages replaced by a neutral formacetal group. The results obtained from monosubstitutions show that no single phosphodiester group is critical for the thrombin inhibitory activity, suggesting that the interaction between the oligodeoxynucleotide and thrombin is based on a multiple-site charge-charge interaction. Analysis of the effects of different phosphodiester replacements indicates that the backside and left side of the chairlike structure formed by the molecule may be involved in binding with thrombin, presumably by having direct contacts with the anion-binding exosite of the enzyme. For the oligodeoxynucleotides containing two noncontiguous formacetal groups, the effect of the disubstitution is the sum of the effects obtained from the corresponding two monosubstitutions. Infusion of an oligodeoxynucleotide containing four formacetal groups into monkeys showed an increased in vivo anticoagulant effect and an extended in vivo half-life compared to the unmodified oligodeoxynucleotide.