4'-C-(2-azidoethyl)-5'-O-(dimethoxytrityl)thymidine | 267244-00-8

• 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: 4'-C-(2-azidoethyl)-5'-O-(dimethoxytrityl)thymidine
• CAS: 267244-00-8
• 化学式: C₃₃H₃₅N₅O₇
• 分子量: 613.67
• InChiKey: IRKITCURAULWAM-NPLMNSEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.59
• 重原子数：
  45.0
• 可旋转键数：
  12.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  160.77
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  4'-C-(2-azidoethyl)-5'-O-(dimethoxytrityl)thymidine 在 10percent Pd/C 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 1-{(2R,4S,5R)-5-(2-Amino-ethyl)-5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-5-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Highly Nuclease-Resistant Phosphodiester-Type Oligodeoxynucleotides Containing 4‘α-C-Aminoalkylthymidines Form Thermally Stable Duplexes with DNA and RNA. A Candidate for Potent Antisense Molecules

  摘要：

  The properties of phosphodiester oligodeoxynucleotides (ODNs) containing 4'alpha-C-aminomethyl, -ethyl, -propyl, and -N-(2-aminoethyl)carbamoylthymidines (1, 2, 4, and 5) as potential antisense molecules are investigated in detail. We developed new radical chemistry with a vinylsilyl or an allylsilyl;I group as a temporary radical acceptor tether to synthesize the required 4'alpha-branched thymidines. Thus, an intramolecular radical cyclization of 4'-phenylseleno nucleosides 7a and 7b, which have a dimethylvinylsilyl and a dimethylallylsilyl group at the 3'-hydroxyl, respectively, with Bu3SnH/AIBN and subsequent Tamao oxidation provided 5'-O-[dimethoxytrityl(DMTr)]-4'alpha-C-(2-hydroxyethyl)thymidine (8a) and 5'-O-DMTr-4'alpha-C-(3-hydroxypropyl)thymidine (8b). Compounds 8a and 8b were then converted into 4'alpha-C-(2-trifluoroacetamidoethyl)thymidine 12a and 4'alpha-C-(3-trifluoroacetamidopropyl)thymid 12b, which were phosphitylated to give the phosphoramidite units 14a and 14b. The phosphoramidite units of 1 and 5 were prepared by previous methods. The nucleosides 1, 2, 1, and 5 were incorporated into the 18-mer, 5'-d[MTMTMTMTMTMTMTMTMT]-3' where M is 5-methyl-2'-deoxycytidine, instead of T at various positions. We also prepared a 21-mer ODN 29 with a mixed sequence containing five residues of 2. The ODNs containing the modified nucleosides formed more stable duplexes with complementary DNA than the corresponding unmodified ODN. These ODNs also formed stable duplexes with the complimentary RNA, The ODNs containing the modified nucleosides were significantly resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase 1 (an endonuclease) and were also very stable in PBS containing 50% human serum. It is worthwhile to note that these ODNs contain natural phosphodiester linkages. Furthermore, the duplexes formed by the ODNs containing the modified nucleosides and their complementary RNAs were good substrates for Escherichia coli RNase H and HeLa cell nuclear extracts as a source of human RNase H. Thus. these ODNs were identified as candidates for antisense molecules.

  DOI：

  10.1021/ja9934706
• 作为产物：
  描述：

  在 sodium azide 、 四丁基氟化铵 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 4'-C-(2-azidoethyl)-5'-O-(dimethoxytrityl)thymidine
  参考文献：
  名称：

  Highly Nuclease-Resistant Phosphodiester-Type Oligodeoxynucleotides Containing 4‘α-C-Aminoalkylthymidines Form Thermally Stable Duplexes with DNA and RNA. A Candidate for Potent Antisense Molecules

  摘要：

  The properties of phosphodiester oligodeoxynucleotides (ODNs) containing 4'alpha-C-aminomethyl, -ethyl, -propyl, and -N-(2-aminoethyl)carbamoylthymidines (1, 2, 4, and 5) as potential antisense molecules are investigated in detail. We developed new radical chemistry with a vinylsilyl or an allylsilyl;I group as a temporary radical acceptor tether to synthesize the required 4'alpha-branched thymidines. Thus, an intramolecular radical cyclization of 4'-phenylseleno nucleosides 7a and 7b, which have a dimethylvinylsilyl and a dimethylallylsilyl group at the 3'-hydroxyl, respectively, with Bu3SnH/AIBN and subsequent Tamao oxidation provided 5'-O-[dimethoxytrityl(DMTr)]-4'alpha-C-(2-hydroxyethyl)thymidine (8a) and 5'-O-DMTr-4'alpha-C-(3-hydroxypropyl)thymidine (8b). Compounds 8a and 8b were then converted into 4'alpha-C-(2-trifluoroacetamidoethyl)thymidine 12a and 4'alpha-C-(3-trifluoroacetamidopropyl)thymid 12b, which were phosphitylated to give the phosphoramidite units 14a and 14b. The phosphoramidite units of 1 and 5 were prepared by previous methods. The nucleosides 1, 2, 1, and 5 were incorporated into the 18-mer, 5'-d[MTMTMTMTMTMTMTMTMT]-3' where M is 5-methyl-2'-deoxycytidine, instead of T at various positions. We also prepared a 21-mer ODN 29 with a mixed sequence containing five residues of 2. The ODNs containing the modified nucleosides formed more stable duplexes with complementary DNA than the corresponding unmodified ODN. These ODNs also formed stable duplexes with the complimentary RNA, The ODNs containing the modified nucleosides were significantly resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3'-exonuclease) and DNase 1 (an endonuclease) and were also very stable in PBS containing 50% human serum. It is worthwhile to note that these ODNs contain natural phosphodiester linkages. Furthermore, the duplexes formed by the ODNs containing the modified nucleosides and their complementary RNAs were good substrates for Escherichia coli RNase H and HeLa cell nuclear extracts as a source of human RNase H. Thus. these ODNs were identified as candidates for antisense molecules.

  DOI：

  10.1021/ja9934706