(1R,5R,6R,8S)-3-aza-8-benzyloxy-1-benzyloxymethyl-6-(thymin-1-yl)-4,7-dioxabicyclo[3.2.1]octan-2-one | 1346636-94-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1R,5R,6R,8S)-3-aza-8-benzyloxy-1-benzyloxymethyl-6-(thymin-1-yl)-4,7-dioxabicyclo[3.2.1]octan-2-one
• 英文别名: 5-methyl-1-[(1R,5R,7R,8S)-4-oxo-8-phenylmethoxy-5-(phenylmethoxymethyl)-2,6-dioxa-3-azabicyclo[3.2.1]octan-7-yl]pyrimidine-2,4-dione
• CAS: 1346636-94-9
• 化学式: C₂₅H₂₅N₃O₇
• 分子量: 479.489
• InChiKey: XFUNBORGEJREFG-BVVSVSJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,5R,6R,8S)-3-aza-8-benzyloxy-1-benzyloxymethyl-6-(thymin-1-yl)-4,7-dioxabicyclo[3.2.1]octan-2-one 在 20% palladium hydroxide on charcoal 、 氢气 作用下， 以 乙醇 、 氯仿 为溶剂， 以80%的产率得到(1R,5R,6R,8S)-3-aza-8-hydroxy-1-hydroxymethyl-6-(thymin-1-yl)-4,7-dioxabicyclo[3.2.1]octan-2-one
  参考文献：
  名称：

  Synthesis and Properties of a Bridged Nucleic Acid with a Perhydro-1,2-oxazin-3-one Ring

  摘要：

  A novel derivative of 2',4'-bridged nucleic acid, named hydroxamate-bridged nucleic acid (HxNA), containing a six-membered perhydro-1,2-oxazin-3-one ring, was designed and synthesized. The introduction of a carbonyl function along with an N-O linkage in the six-membered bridged structure is the unique structural feature of the novel 2',4'-bridged nucleic acid analogue. The design was carried out to restrict the flexibility of the sugar moiety through the trigonal planarity of carbonyl function, which would improve the properties of the modification. The synthesized monomer was incorporated into oligonucleotides, and their properties were examined. The HxNA-modified oligonucleotides exhibited selectively high affinity toward complementary ssRNA. Furthermore, the nuclease resistance of the HxNA-modified oligonucleotide was found to be higher than that of the corresponding natural and 2',4'-BNA/LNA-modified oligonucleotides. Interestingly, exposure of HxNA modified oligonucleotide to 3'-exonuclease resulted in gradual opening of the bridge, which stopped further digestion. Moreover, ring-opening of only one modification at the 3'-end of the oligonucleotides was observed, even if two or three HxNA modifications were present in the sequence. The results demonstrate the strong potential of the HxNA modification as a switch for the generation of highly nuclease-resistant RNA selective oligonucleotide in situ, which could have potential applications in antisense technology.

  DOI：

  10.1021/jo201597e
• 作为产物：
  描述：

  2'-O-amino-3',5'-di-O-benzyl-4'-carboxy-5-methyluridine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 以240 mg的产率得到(1R,5R,6R,8S)-3-aza-8-benzyloxy-1-benzyloxymethyl-6-(thymin-1-yl)-4,7-dioxabicyclo[3.2.1]octan-2-one
  参考文献：
  名称：

  Synthesis and Properties of a Bridged Nucleic Acid with a Perhydro-1,2-oxazin-3-one Ring

  摘要：

  A novel derivative of 2',4'-bridged nucleic acid, named hydroxamate-bridged nucleic acid (HxNA), containing a six-membered perhydro-1,2-oxazin-3-one ring, was designed and synthesized. The introduction of a carbonyl function along with an N-O linkage in the six-membered bridged structure is the unique structural feature of the novel 2',4'-bridged nucleic acid analogue. The design was carried out to restrict the flexibility of the sugar moiety through the trigonal planarity of carbonyl function, which would improve the properties of the modification. The synthesized monomer was incorporated into oligonucleotides, and their properties were examined. The HxNA-modified oligonucleotides exhibited selectively high affinity toward complementary ssRNA. Furthermore, the nuclease resistance of the HxNA-modified oligonucleotide was found to be higher than that of the corresponding natural and 2',4'-BNA/LNA-modified oligonucleotides. Interestingly, exposure of HxNA modified oligonucleotide to 3'-exonuclease resulted in gradual opening of the bridge, which stopped further digestion. Moreover, ring-opening of only one modification at the 3'-end of the oligonucleotides was observed, even if two or three HxNA modifications were present in the sequence. The results demonstrate the strong potential of the HxNA modification as a switch for the generation of highly nuclease-resistant RNA selective oligonucleotide in situ, which could have potential applications in antisense technology.

  DOI：

  10.1021/jo201597e

文献信息

• Synthesis and Properties of a Bridged Nucleic Acid with a Perhydro-1,2-oxazin-3-one Ring
  作者：Ajaya R. Shrestha、Yoshiyuki Hari、Aiko Yahara、Takashi Osawa、Satoshi Obika

  DOI：10.1021/jo201597e

  日期：2011.12.16

  A novel derivative of 2',4'-bridged nucleic acid, named hydroxamate-bridged nucleic acid (HxNA), containing a six-membered perhydro-1,2-oxazin-3-one ring, was designed and synthesized. The introduction of a carbonyl function along with an N-O linkage in the six-membered bridged structure is the unique structural feature of the novel 2',4'-bridged nucleic acid analogue. The design was carried out to restrict the flexibility of the sugar moiety through the trigonal planarity of carbonyl function, which would improve the properties of the modification. The synthesized monomer was incorporated into oligonucleotides, and their properties were examined. The HxNA-modified oligonucleotides exhibited selectively high affinity toward complementary ssRNA. Furthermore, the nuclease resistance of the HxNA-modified oligonucleotide was found to be higher than that of the corresponding natural and 2',4'-BNA/LNA-modified oligonucleotides. Interestingly, exposure of HxNA modified oligonucleotide to 3'-exonuclease resulted in gradual opening of the bridge, which stopped further digestion. Moreover, ring-opening of only one modification at the 3'-end of the oligonucleotides was observed, even if two or three HxNA modifications were present in the sequence. The results demonstrate the strong potential of the HxNA modification as a switch for the generation of highly nuclease-resistant RNA selective oligonucleotide in situ, which could have potential applications in antisense technology.