(1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(hypoxanthin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane | 293751-43-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(hypoxanthin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(hypoxantin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane；(1R,3R,4R,7S)-1-(4,4'-Dimethoxytrityloxymethyl)-7-hydroxy-3-(hypoxantin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane；9-[(1R,3R,4R,7S)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-1H-purin-6-one
• CAS: 293751-43-6
• 化学式: C₃₂H₃₀N₄O₇
• 分子量: 582.613
• InChiKey: OYQBCEZKHJJFOD-QGBBYCRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  双(二异丙基氨基)(2-氰基乙氧基)膦 、 (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(hypoxanthin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 二氯特诺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 2.0h， 以91%的产率得到(1R,3R,4R,7S)-7-(2-cyanoethoxy(diiospropylamino)phosphinoxy)-1-(4,4'-dimethoxytrityloxymethyl)-3-(hypoxanthin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Koshkin, Alexei A., Journal of Organic Chemistry, 2004, vol. 69, # 11, p. 3711 - 3718

  摘要：

  DOI：
• 作为产物：
  描述：

  (1S,3R,4R,7S)-7-benzyloxy-3-(hypoxanthin-9-yl)-1-methanesulfonyloxymethyl-2,5-dioxabicyclo[2.2.1]heptane 在 palladium on activated charcoal 吡啶 、 sodium hydroxide 、 甲酸甲酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(hypoxanthin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Koshkin, Alexei A., Journal of Organic Chemistry, 2004, vol. 69, # 11, p. 3711 - 3718

  摘要：

  DOI：

文献信息

• Synthesis of [2.2.1]bicyclo nucleosides
  申请人：Exiqon A/S

  公开号：US20030092905A1

  公开（公告）日：2003-05-15

  A synthesis of [2.2.1]bicyclo nucleosides which is shorter and provides higher overall yields proceeds via the key intermediate of the general formula III, wherein R 4 and R 5 are, for instance, sulfonates and R 7 is, for instance, a halogen or an acetate. From compounds of the general formula II, such as 3-O-aryl-4-C-hydroxymethyl-1,2-O-isopropylidene-&agr;-D-ribofuranose, intermediates of the general formula III are suitable for coupling with silylated nucleobases. Upon one-pot base-induced ring-closure and desulfonation of the formed [2.2.1]bicyclo nucleoside, a short route to each the LNA (Locked Nucleic Acid) derivatives of adenosine, cytosine, uridine, thymidine and guanidine is demonstrated. The use of the 5′-sulfonated ring-closed intermediate also allows for synthesis of 5′-amino- and thio-LNAs. 1

  一种合成[2.2.1]双环核苷的方法，该方法更短且提供更高的总收率，通过通式III的关键中间体进行，其中R4和R5例如为磺酸酯，R7例如为卤素或乙酸酯。从通式II的化合物，例如3-O-芳基-4-C-羟甲基-1,2-O-异丙基亚-D-核糖，适合与硅烷基化的核碱基偶联的通式III的中间体。通过一锅法碱诱导的环闭合和去磺酸化形成[2.2.1]双环核苷，演示了腺嘌呤、胞嘧啶、尿嘧啶、胸腺嘧啶和鸟嘌呤的LNA（锁定核酸）衍生物的短路线。使用5'-磺酸化的环闭合中间体还允许合成5'-氨基和硫代LNA。
• Synthesis of [2.2.1]bicyclo nucleosides
  申请人：Exiqon A/S

  公开号：US06639059B1

  公开（公告）日：2003-10-28

  A synthesis of [2.2.1]bicyclo nucleosides which is shorter and provides higher overall yields proceeds via the key intermediate of the general formula III, wherein R4 and R5 are, for instance, sulfonates and R7 is, for instance, a halogen or an acetate. From compounds of the general formula II, such as 3-O-aryl-4-C-hydroxymethyl-1,2-O-isopropylidene-&agr;-D-ribofuranose, intermediates of the general formula III are suitable for coupling with silylated nucleobases. Upon one-pot base-induced ring-closure and desulfonation of the formed [2.2.1]bicyclo nucleoside, a short route to each the LNA (Locked Nucleic Acid) derivatives of adenosine, cytosine, uridine, thymidine and guanidine is demonstrated. The use of the 5′-sulfonated ring-closed intermediate also allows for synthesis of 5′-amino- and thio-LNAs.

  通过通用式III的关键中间体进行合成，该合成方法可制得较短且总收率较高的[2.2.1]双环核苷。在通用式II化合物（例如3-O-芳基-4-C-羟甲基-1,2-O-异丙基亚-D-核糖）的基础上，通用式III的中间体适合与硅化核碱基耦合。在一锅法碱诱导的环闭合和去磺酸化反应中，形成的[2.2.1]双环核苷可快速合成腺嘌呤、胞嘧啶、尿嘧啶、胸腺嘧啶和鸟嘌呤的LNA（锁定核酸）衍生物。使用5'-磺酸化的环闭合中间体还允许合成5'-氨基和硫代-LNA。
• IMPROVED SYNTHESIS OF ¬2.2.1|BICYCLO NUCLEOSIDES
  申请人：Exiqon A/S

  公开号：EP1163250B1

  公开（公告）日：2006-07-12