(1S,3R,4R,7S)-3-(6-N-benzoyladenine-9-yl)-7-hydroxy-1-hydroxymethyl-2,5-dioxabicyclo[2.2.1]heptane | 209968-94-5

• 物质功能分类: 有机原料 - 杂环化合物
• 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: (1S,3R,4R,7S)-3-(6-N-benzoyladenine-9-yl)-7-hydroxy-1-hydroxymethyl-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: (1S,3R,4R,7S)-7-hydroxy-1-hydroxymethyl-3-(6-N-benzoyladenin-9-yl)-2,5-dioxabicyclo-[2.2.1]heptane；N6-Benzoyl-2'-O,4'-C-methyleneadenosine；N-[9-[(1S,3R,4R,7S)-7-hydroxy-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl]purin-6-yl]benzamide
• CAS: 209968-94-5
• 化学式: C₁₈H₁₇N₅O₅
• 分子量: 383.363
• InChiKey: LWLHBOKWFIOXPA-OBQMCUGOSA-N

物化性质

• 密度：
  1.74±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1S,3R,4R,7S)-3-(6-N-benzoyladenine-9-yl)-7-hydroxy-1-hydroxymethyl-2,5-dioxabicyclo[2.2.1]heptane 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 Diisopropyl-phosphoramidous acid (1R,3R,4R,7S)-3-(6-benzoylamino-purin-9-yl)-1-[(4-methoxy-phenyl)-(3-methoxy-phenyl)-phenyl-methoxymethyl]-2,5-dioxa-bicyclo[2.2.1]hept-7-yl ester 2-cyano-ethyl ester
  参考文献：
  名称：

  LNA（锁定核酸）：腺嘌呤，胞嘧啶，鸟嘌呤，5-甲基胞嘧啶，胸腺嘧啶和尿嘧啶双环核苷单体的合成，寡聚化和前所未有的核酸识别

  摘要：

  由2'- O，4'- C-亚甲基双环核苷单体组成的LNA（锁定核酸）被有效合成，并评估了其对六种不同核碱基（腺嘌呤，胞嘧啶，鸟嘌呤，5-甲基胞嘧啶，胸腺嘧啶）的核酸识别潜力和尿嘧啶。当评估部分或完全修饰的LNA的混合序列时，双链体对DNA和RNA的热稳定性出现了前所未有的提高（每个修饰+3至+8°C）。错配序列的研究表明，与相应的未修饰参考链相比，LNA遵循具有普遍提高的选择性的Watson-Crick碱基配对规则。

  DOI：

  10.1016/s0040-4020(98)00094-5
• 作为产物：
  描述：

  (1R,3R,4R,7S)-3-(adenine-9-yl)-7-benzyloxy-1-methanesulfonoxymethyl-2,5-dioxabicyclo[2.2.1]heptane 在 palladium dihydroxide 吡啶 、 sodium hydroxide 、 甲酸铵 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.25h， 生成 (1S,3R,4R,7S)-3-(6-N-benzoyladenine-9-yl)-7-hydroxy-1-hydroxymethyl-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  通往2'-O，4'-C-亚甲基连接的双环核糖核苷（锁定核酸）的简便有效途径。

  摘要：

  描述了一种合成锁核酸（LNA）单体的新型有效方法。通过聚合合成制备了含有胸腺嘧啶，4-N-乙酰基和4-N-苯甲酰基胞嘧啶，6-N-苯甲酰腺嘌呤和2-N-异丁酰鸟嘌呤作为核碱基的LNA 5'，3'-二醇。该方法基于使用常见的糖中间体1,2-二-O-乙酰基-3-O-苄基-4-C-甲磺酰氧基甲基-5-O-甲磺酰-D-赤型戊呋喃糖（8）可以从D-葡萄糖以克数制得。使用改良的Vorbrüggen程序将四个不同的核碱基立体选择性地偶联到8个核碱基上，得到相应的4'-C-支链核苷衍生物。随后的闭环提供了受保护的LNA核苷。使用苯甲酸钠通过亲核取代有效地置换了5'-O-甲磺酰基。将5'-苯甲酸酯皂化，然后催化除去3'-O-苄基，得到游离的LNA二醇。腺苷和胞苷的环外氨基被选择性地酰化，得到4-N-乙酰基或4-N-苯甲酰基-LNA-C和6-N-苯甲酰基-LNA-A。在制备2-N-异丁酰基-LNA-G期间，鸟

  DOI：

  10.1021/jo010732p
• 作为试剂：
  描述：

  (1S,3R,4R,7S)-7-Benzyloxy-1-benzoyloxymethyl-3-(adenin-9-yl)-2,5-dioxabicyclo-[2.2.1]heptane 、 苯甲酰氯 在 氢氧化钯 吡啶 、 ice 、 二氯甲烷 、 pyridine methanol 、 sodium hydroxide 、 methanol-dichloromethane 、 (1S,3R,4R,7S)-3-(6-N-benzoyladenine-9-yl)-7-hydroxy-1-hydroxymethyl-2,5-dioxabicyclo[2.2.1]heptane 作用下， 以 Methanol cyclohexene 、 methanol-dichloromethane 为溶剂， 反应 36.25h， 以to yield 0.54 g (70%) of glass-like solid material with the same chromatographic mobility as authentic compound的产率得到(1S,3R,4R,7S)-3-(6-N-benzoyladenine-9-yl)-7-hydroxy-1-hydroxymethyl-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis of [2.2.1]bicyclo nucleosides

  摘要：

  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。

  公开号：

  US20030092905A1

文献信息

• Novel convenient syntheses of LNA [2.2.1]bicyclo nucleosides
  作者：Alexei A. Koshkin、Vivek K. Rajwanshi、Jesper Wengel

  DOI：10.1016/s0040-4039(98)00706-0

  日期：1998.6

  oligonucleotide analogue containing [2.2.1]bicyclo nucleoside monomers. A novel and significantly improved method for convergent synthesis of LNA [2.2.1]bicyclo nucleosides using a 4-C-tosyloxymethyl-1, 2-di-O-acetyl furanose as a key synthon is described. In addition, an alternative, robust linear approach allowing selective formation of the desired [2.2.1]bicyclo LNA nucleosides via a tricyclic nucleoside

  LNA（锁定核酸）是一种新型的寡核苷酸类似物，含有[2.2.1]双环核苷单体。描述了一种新颖且显着改进的方法，该方法使用4-C-甲苯磺酰氧基甲基-1，2-二-O-乙酰基呋喃糖作为关键合成子，聚合合成LNA [2.2.1]双环核苷。此外，介绍了一种替代的，稳健的线性方法，该方法允许通过三环核苷中间体选择性形成所需的[2.2.1]双环LNA核苷。
• Oligonucleotide analogues
  申请人：Wengel Jesper

  公开号：US20050287566A1

  公开（公告）日：2005-12-29

  The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs (Locked Nucleoside Analogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.

  本发明涉及新型的双环和三环核苷酸和核苷酸类似物，以及包含这些元素的寡核苷酸。这些核苷酸类似物，即锁定核苷酸类似物（LNAs），能够为寡核苷酸提供与互补RNA和DNA寡聚物的亲和力和特异性方面的有价值的改进。这种新型的LNA修饰的寡核苷酸以及LNA本身在广泛的诊断应用和治疗应用中非常有用。其中包括反义应用、PCR应用、链置换寡聚物、作为核酸聚合酶的底物、作为基于核苷酸的药物等。本发明还涉及这些应用。
• 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。
• OLIGONUCLEOTIDE ANALOGUES
  申请人：Wengel Jesper

  公开号：US20100279895A1

  公开（公告）日：2010-11-04

  The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs (Locked Nucleoside Analogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.

  本发明涉及新型的双环和三环核苷酸和核苷酸类似物，以及包含这些元素的寡核苷酸。这些核苷酸类似物，即LNAs（锁定核苷酸类似物），能够为寡核苷酸提供与互补RNA和DNA寡聚物相比亲和力和特异性的有价值的改进。这种新型的LNA修饰的寡核苷酸以及LNAs本身在广泛的诊断应用和治疗应用中都有用途。其中可以提到反义应用、PCR应用、链位移寡聚物、作为核酸聚合酶底物、作为核苷酸基药物等。本发明还涉及这些应用。
• Oligonucleotide Analogues
  申请人：WENGEL Jesper

  公开号：US20110245327A1

  公开（公告）日：2011-10-06

  The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs ( L ocked N ucleoside A nalogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.

  本发明涉及新型的双环和三环核苷酸和核苷酸类似物，以及包含这些元素的寡核苷酸。核苷酸类似物，即锁定核苷酸类似物（LNAs），能够为寡核苷酸提供有价值的改进，使其对互补的RNA和DNA寡聚体具有更高的亲和力和特异性。这种新型的LNA修饰的寡核苷酸以及LNAs本身在广泛的诊断应用和治疗应用中都很有用。其中包括反义应用、PCR应用、链置换寡聚体、作为核酸聚合酶的底物、作为基于核苷酸的药物等。本发明还涉及这些应用。