(1R,3R,4R,7R)-7-benzoyloxy-1-methanesulfonyloxymethyl-3-(thymin-1-yl)-2-oxa-5-thiabicyclo[2.2.1]heptane | 625111-35-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,3R,4R,7R)-7-benzoyloxy-1-methanesulfonyloxymethyl-3-(thymin-1-yl)-2-oxa-5-thiabicyclo[2.2.1]heptane
• 英文别名: (1R,3R,4R,7R)-7-benzoyloxy-1-methansulfonyloxymethyl-3-(thymin-1-yl)-2-oxa-5-thiabicyclo[2.2.1]heptane；(1R,3R,4R,7R)-7-benzoyloxy-1-methansulfonyloxymethyl-3-(thymin-1-yl)-2-oxa-5-thiabicyclo[2:2:1]heptane；[(1R,3R,4R,7R)-3-(5-methyl-2,4-dioxopyrimidin-1-yl)-1-(methylsulfonyloxymethyl)-2-oxa-5-thiabicyclo[2.2.1]heptan-7-yl] benzoate
• CAS: 625111-35-5
• 化学式: C₁₉H₂₀N₂O₈S₂
• 分子量: 468.508
• InChiKey: BFVBKXLQWCDISX-DZASIIFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  162
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (1R,3R,4R,7R)-7-benzoyloxy-1-methanesulfonyloxymethyl-3-(thymin-1-yl)-2-oxa-5-thiabicyclo[2.2.1]heptane 在 sodium benzoate 作用下， 以 甲醇 、 正庚烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 以81%的产率得到(1R,3R,4R,7R)-7-benzoyloxy-1-benzoyloxymethyl-3-(thymin-1-yl)-2-oxa-5-thiabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Oligomeric compounds for the modulation of thioredoxin expression

  摘要：

  提供针对TRX基因的寡核苷酸，用于调节TRX的表达。这些组合物包括寡核苷酸，特别是针对编码TRX的核酸的反义寡核苷酸。提供了使用这些化合物调节TRX表达和治疗与TRX过度表达、突变TRX表达或两者都相关的疾病的方法。疾病的例子包括肺癌、乳腺癌、结肠癌、前列腺癌、胰腺癌、肝癌、甲状腺癌、肾癌、脑癌、睾丸癌、胃癌、肠癌、脊髓癌、鼻窦癌、膀胱癌、泌尿道癌或卵巢癌等。这些寡核苷酸可以由脱氧核苷酸或核酸类似物组成，例如锁定核酸或二者的组合。

  公开号：

  US20040241717A1
• 作为产物：
  描述：

  2,2'-anhydro-1-(3-O-benzoyl-5-O-methanesulfonyl-4-C-methanesulfonyloxymethyl-β-D-threo-pentofuranosyl)thymine 在 吡啶 、 4-二甲氨基吡啶 、 sodium sulfide 、 硫酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 (1R,3R,4R,7R)-7-benzoyloxy-1-methanesulfonyloxymethyl-3-(thymin-1-yl)-2-oxa-5-thiabicyclo[2.2.1]heptane
  参考文献：
  名称：

  LNA（锁定核酸）的类似物：2'-硫代-LNA 核苷和 5-甲基胞苷亚磷酰胺的合成

  摘要：

  使用使 2'-硫代-LNA 的合成与 LNA 和 2'-氨基-LNA 的合成趋同的策略合成了双环 2'-硫代-LNA 核胸苷亚磷酰胺 (13)。关键步骤是形成脱水核苷 4，它可以防止在 3'-OBn 基团的脱苄基化过程中形成不需要的氧杂环丁烷 (3)，同时在 C2' 位置提供必要的构型反转。即使在碱性条件下也没有观察到氧杂环丁烷。我们认为这是由于刚性三环脱水核苷限制了呋喃糖的构象自由度，从而阻止了应变四环系统的形成。除去苄基保护基团后，游离的 3' -OH 基团 (5) 很容易被苯甲酰化 (6) 并且脱水核苷环打开以产生苏式构型的核苷 7。 2'-硫代-LNA 核胸苷亚磷酰胺由脱水核苷 4 分 9 步合成，产率为 30% . 使用标准方案从核苷 12 合成 2'-硫代-LNA 5-甲基胞苷亚磷酰胺。

  DOI：

  10.1055/s-2004-815959

文献信息

• [EN] SYNTHESIS OF LOCKED NUCLEIC ACID DERIVATIVES<br/>[FR] SYNTHÈSE DE DÉRIVÉS D'ACIDES NUCLÉIQUES LNA
  申请人：SANTARIS PHARMA AS

  公开号：WO2003095467A1

  公开（公告）日：2003-11-20

  The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as α-L-oxy-LNA, amino-LNA, α-L-amino-LNA, thio-LNA, α-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues. (Formula I)

  该发明涉及一种用于合成锁定核酸衍生物的新策略，例如α-L-氧基-LNA、氨基-LNA、α-L-氨基-LNA、硫基-LNA、α-L-硫基-LNA、硒基-LNA和亚甲基-LNA，该策略利用中间体进行可扩展高产率反应，这些中间体还可以产生其他LNA类似物，如氧基-LNA。此外，式X的化合物是重要的中间体，可以与多种亲核试剂发生反应，从而形成各种LNA类似物。
• Synthesis of locked nucleic acid derivatives
  申请人：——

  公开号：US20040014959A1

  公开（公告）日：2004-01-22

  The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as &agr;-L-oxy-LNA, amino-LNA, &agr;-L-amino-LNA, thio-LNA, &agr;-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues. 1

  该发明涉及一种用于合成锁定核酸衍生物的新策略，例如α-L-氧基-LNA、氨基-LNA、α-L-氨基-LNA、硫基-LNA、α-L-硫基-LNA、硒基-LNA和亚甲基-LNA，该策略利用中间体进行可扩展的高产率反应，这些中间体还可以产生其他LNA类似物，如氧基-LNA。另外，公式X的化合物是重要的中间体，可以与多种亲核试剂反应，生成各种LNA类似物。
• Oligomeric compounds for the modulation survivin expression
  申请人：Hansen Bo

  公开号：US20050014712A1

  公开（公告）日：2005-01-20

  Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

  提供针对survivin基因的寡核苷酸，用于调节survivin的表达。这些组合物包括寡核苷酸，特别是针对编码survivin的核酸的反义寡核苷酸。提供使用这些化合物调节survivin表达和治疗与survivin过度表达，表达突变survivin或两者都有关的疾病的方法。疾病的例子是癌症，如肺癌，乳腺癌，结肠癌，前列腺癌，胰腺癌，肝癌，甲状腺癌，肾癌，脑癌，睾丸癌，胃癌，肠道癌，脊髓癌，鼻窦癌，膀胱癌，泌尿道或卵巢癌。寡核苷酸可以由脱氧核糖核苷或核酸类似物组成，例如锁定核酸酸或两者的组合。
• Oligomeric compounds for the modulation of ras expression
  申请人：Santaris Pharma A/S

  公开号：US20040248840A1

  公开（公告）日：2004-12-09

  Oligonucleotides directed against the Ha-ras gene are provided for modulating the expression of Ha-ras. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the Ha-ras. Methods of using these compounds for modulation of Ha-ras expression and for the treatment of diseases associated with either overexpression of Ha-ras, expression of mutated Ha-ras or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

  提供了针对Ha-ras基因的寡核苷酸，用于调节Ha-ras的表达。该组成物包括针对编码Ha-ras的核酸的寡核苷酸，特别是反义寡核苷酸。提供了使用这些化合物调节Ha-ras表达和治疗与Ha-ras过度表达、突变Ha-ras表达或两者都有关的疾病的方法。疾病的例子包括肺癌、乳腺癌、结肠癌、前列腺癌、胰腺癌、肝癌、甲状腺癌、肾癌、脑癌、睾丸癌、胃癌、肠癌、脊髓癌、鼻窦癌、膀胱癌、泌尿道癌或卵巢癌。寡核苷酸可以由脱氧核苷酸或核酸类似物组成，例如锁定核酸或两者的组合。
• Oligomeric compounds for the modulation ras expression
  申请人：Hansen Bo

  公开号：US20080188432A1

  公开（公告）日：2008-08-07

  Oligonucleotides directed against the Ha-ras gene are provided for modulating the expression of Ha-ras. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the Ha-ras. Methods of using these compounds for modulation of Ha-ras expression and for the treatment of diseases associated with either overexpression of Ha-ras, expression of mutated Ha-ras or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

  本发明提供了针对Ha-ras基因的寡核苷酸，用于调节Ha-ras的表达。该组合物包括寡核苷酸，特别是针对编码Ha-ras的核酸的反义寡核苷酸。提供了使用这些化合物调节Ha-ras表达以及治疗与Ha-ras过度表达，突变Ha-ras表达或两者都有关的疾病的方法。疾病的例子是癌症，如肺癌、乳腺癌、结肠癌、前列腺癌、胰腺癌、肝癌、甲状腺癌、肾癌、脑癌、睾丸癌、胃癌、肠癌、脊髓、鼻窦、膀胱、泌尿道或卵巢癌。寡核苷酸可以由脱氧核苷酸或核酸类似物组成，例如锁定核酸或其组合。