N⁶-benzoyl-5'-butyl-3'-O-[(tert-butyl)dimethylsilyl]-2'-deoxyadenosine

• 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: N⁶-benzoyl-5'-butyl-3'-O-[(tert-butyl)dimethylsilyl]-2'-deoxyadenosine
• 英文别名: N-[9-[(2R,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(1-hydroxypentyl)oxolan-2-yl]purin-6-yl]benzamide
• 化学式: C₂₇H₃₉N₅O₄Si
• 分子量: 525.723
• InChiKey: MLASUMRPSYBVQH-ITAUKHEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.31
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-benzoyl-O3'-(tert-butyldimethylsilyl)-5'-oxo-2'-deoxyadenosine 在 copper(l) iodide 、 sodium hexamethyldisilazane 、 二甲基二环氧乙烷 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 80.0h， 生成 N⁶-benzoyl-5'-butyl-3'-O-[(tert-butyl)dimethylsilyl]-2'-deoxyadenosine
  参考文献：
  名称：

  Synthesis of (5′S)-5′-C-Alkyl-2′-deoxynucleosides

  摘要：

  We describe the synthesis of (S'S)-5'-C-butylthymidine (5a), of the (S'S)-5'-C-butyl- and the (5'S)-5'-C-isopentyl derivatives 16a and 16b of 2'-deoxy-5-methylcytidine, as well as of the corresponding cyanoethyl phosphoramidites 9a,b and 14a,b, respectively. Starting from thymidin-5'-al 1, the alkyl chain at C(5') is introduced via Wittig chemistry to selectively yield the (Z)-olefin derivatives 3a and 3b (Scheme 2). The secondary OH function at C(5') is then introduced by epoxidation followed by regioselective reduction of the epoxy derivatives 4a and 4b with diisobutylaluminium hydride. In the latter step, a kinetic resolution of the diastereoisomer mixture 4a and 4b occurs, yielding the alkylated nucleoside 2a and 2b, respectively, with (5'S)configuration in high diastereoisomer purity (de=94%). The corresponding 2'-deoxy-5-methylcytidine derivatives are obtained from the protected 5'-alkylated thymidine derivatives 7a and 7b via known base interconversion processes in excellent yields (Scheme 3). Application of the same strategy to the purine nucleoside 2'-deoxyadenine to obtain 5'-C-butyl-2'-deoxyadenosine 25 proved to be difficult due to the sensitivity of the purine base to hydride-based reducing agents (Scheme 4).

  DOI：

  10.1002/1522-2675(20010131)84:1<87::aid-hlca87>3.0.co;2-1

文献信息

• Synthesis of (5′S)-5′-C-Alkyl-2′-deoxynucleosides
  作者：Huldreich Trafelet、Eugen Stulz、Christian Leumann

  DOI：10.1002/1522-2675(20010131)84:1<87::aid-hlca87>3.0.co;2-1

  日期：2001.1.31

  We describe the synthesis of (S'S)-5'-C-butylthymidine (5a), of the (S'S)-5'-C-butyl- and the (5'S)-5'-C-isopentyl derivatives 16a and 16b of 2'-deoxy-5-methylcytidine, as well as of the corresponding cyanoethyl phosphoramidites 9a,b and 14a,b, respectively. Starting from thymidin-5'-al 1, the alkyl chain at C(5') is introduced via Wittig chemistry to selectively yield the (Z)-olefin derivatives 3a and 3b (Scheme 2). The secondary OH function at C(5') is then introduced by epoxidation followed by regioselective reduction of the epoxy derivatives 4a and 4b with diisobutylaluminium hydride. In the latter step, a kinetic resolution of the diastereoisomer mixture 4a and 4b occurs, yielding the alkylated nucleoside 2a and 2b, respectively, with (5'S)configuration in high diastereoisomer purity (de=94%). The corresponding 2'-deoxy-5-methylcytidine derivatives are obtained from the protected 5'-alkylated thymidine derivatives 7a and 7b via known base interconversion processes in excellent yields (Scheme 3). Application of the same strategy to the purine nucleoside 2'-deoxyadenine to obtain 5'-C-butyl-2'-deoxyadenosine 25 proved to be difficult due to the sensitivity of the purine base to hydride-based reducing agents (Scheme 4).