2'-O-amino-3',5'-di-O-benzyl-4'-carboxy-5-methyluridine | 1300590-91-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-O-amino-3',5'-di-O-benzyl-4'-carboxy-5-methyluridine
• 英文别名: (2R,3S,4R,5R)-4-aminooxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-3-phenylmethoxy-2-(phenylmethoxymethyl)oxolane-2-carboxylic acid
• CAS: 1300590-91-3
• 化学式: C₂₅H₂₇N₃O₈
• 分子量: 497.505
• InChiKey: UNPRLWWEUDTDRM-BVVSVSJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  150
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2'-O-amino-3',5'-di-O-benzyl-4'-carboxy-5-methyluridine 在 20% palladium hydroxide on charcoal 、 氢气 、 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 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 (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：

  [(2R,3S,4S,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-phenylmethoxy-5-(phenylmethoxymethyl)oxolan-3-yl] trifluoromethanesulfonate 在 重铬酸吡啶 、 一水合肼 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 triethylamine tris(hydrogen fluoride) 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 58.17h， 生成 2'-O-amino-3',5'-di-O-benzyl-4'-carboxy-5-methyluridine
  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

• BRIDGED ARTIFICIAL NUCLEOSIDE AND NUCLEOTIDE
  申请人：Obika Satoshi

  公开号：US20120208991A1

  公开（公告）日：2012-08-16

  It is an object of the present invention to provide a novel molecule for antisense therapies which is not susceptible to nuclease degradation in vivo and has a high binding affinity and specificity for the target mRNAs and which can efficiently regulate expression of specific genes. The novel artificial nucleoside of the present invention has an amide bond introduced into a bridge structure of 2′,4′-BNA/LNA. The oligonucleotide containing the 2′,4′-bridged artificial nucleotide has a binding affinity for a single-stranded RNA comparable to known 2′,4′-BNA/LNA and has an increased nuclease resistance over LNA. Particularly, it is expected to be applied to nucleic acid drugs because of its much stronger binding affinity for single-stranded RNAs than S-oligo's affinity

  本发明的目的是提供一种新型分子用于反义疗法，该分子在体内不易受核酸酶降解，并且对目标mRNA具有高结合亲和力和特异性，能够有效调节特定基因的表达。本发明的新型人工核苷酸在2′,4′-BNA/LNA的桥接结构中引入了酰胺键。含有2′,4′-桥接人工核苷酸的寡核苷酸与已知的2′,4′-BNA/LNA具有相当的单链RNA结合亲和力，并且比LNA具有更高的核酸酶抗性。特别地，由于其比S-oligo对单链RNA的结合亲和力更强，预计将被应用于核酸药物。