9-[1'-O-methanesulfonyl-3',4'-O-acetyl-6'-O-(4-toluoyl)-β-D-psicofuranosyl]-N⁶-benzoyladenine | 478487-96-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 9-[1'-O-methanesulfonyl-3',4'-O-acetyl-6'-O-(4-toluoyl)-β-D-psicofuranosyl]-N⁶-benzoyladenine
• 英文别名: [(2R,3R,4R,5R)-3,4-diacetyloxy-5-(6-benzamidopurin-9-yl)-5-(methylsulfonyloxymethyl)oxolan-2-yl]methyl 4-methylbenzoate
• CAS: 478487-96-6
• 化学式: C₃₁H₃₁N₅O₁₁S
• 分子量: 681.68
• InChiKey: TYKWIDXERMYKHU-RAYZIOHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.14
• 重原子数：
  48.0
• 可旋转键数：
  11.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  204.2
• 氢给体数：
  1.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  9-[1'-O-methanesulfonyl-3',4'-O-acetyl-6'-O-(4-toluoyl)-β-D-psicofuranosyl]-N⁶-benzoyladenine 在 吡啶 、 氨 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 55.5h， 生成 9-[1',3'-O-anhydro-4',6'-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-psicofuranosyl]-N⁶-(phenoxyacetyl)-adenine
  参考文献：
  名称：

  Synthesis, Physicochemical and Biochemical Studies of 1‘,2‘-Oxetane Constrained Adenosine and Guanosine Modified Oligonucleotides, and Their Comparison with Those of the Corresponding Cytidine and Thymidine Analogues

  摘要：

  We have earlier reported the synthesis and antisense properties of the conformationally constrained oxetane-C and -T containing oligonucleotides, which have shown effective down-regulation of the proto-oncogene c-myb mRNA in the K562 human leukemia cells. Here we report on the straightforward syntheses of the oxetane-A and oxetane-G nucleosides as well as their incorporations into antisense oligonucleotides (AONs), and compare their structural and antisense properties with those of the T and C modified AONs (including the thermostability and RNase H recruitment capability of the AON/RNA hybrid duplex by Michaelis-Menten kinetic analyses, their resistance in the human serum, as well as in the presence of exo and endonucleases).

  DOI：

  10.1021/ja048417i
• 作为产物：
  描述：

  2-O-methyl-3,4-O-isopropylidene-6-O-(4-toluoyl)-D-psicofuranose 在 吡啶 、 三甲基氯硅烷 、 氢溴酸 、 溶剂黄146 、 六甲基二硅氮烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 42.42h， 生成 9-[1'-O-methanesulfonyl-3',4'-O-acetyl-6'-O-(4-toluoyl)-β-D-psicofuranosyl]-N⁶-benzoyladenine
  参考文献：
  名称：

  Synthesis, Physicochemical and Biochemical Studies of 1‘,2‘-Oxetane Constrained Adenosine and Guanosine Modified Oligonucleotides, and Their Comparison with Those of the Corresponding Cytidine and Thymidine Analogues

  摘要：

  We have earlier reported the synthesis and antisense properties of the conformationally constrained oxetane-C and -T containing oligonucleotides, which have shown effective down-regulation of the proto-oncogene c-myb mRNA in the K562 human leukemia cells. Here we report on the straightforward syntheses of the oxetane-A and oxetane-G nucleosides as well as their incorporations into antisense oligonucleotides (AONs), and compare their structural and antisense properties with those of the T and C modified AONs (including the thermostability and RNase H recruitment capability of the AON/RNA hybrid duplex by Michaelis-Menten kinetic analyses, their resistance in the human serum, as well as in the presence of exo and endonucleases).

  DOI：

  10.1021/ja048417i

文献信息

• Synthesis of anhydro psicofuranosyl nucleosides
  作者：Jarkko Roivainen、Jouko Vepsäläinen、Alex Azhayev、Igor A. Mikhailopulo

  DOI：10.1016/s0040-4039(02)01472-7

  日期：2002.9

  Methyl 1-O-mesyl-5-O-toluoyl-β-d-psicofuranoside (5) was synthesised from the known 1,3;4,5-di-O-isopropylidene-β-d-psicofuranose (1) as a key carbohydrate precursor for the preparation of anhydro psicofuranosyl nucleosides. Transformation of 5 into acetate 7 or bromide 10 followed by (i) coupling with persilylated N6-benzoyladenine in the presence of SnCl4, and (ii) treatment with MeONa/MeOH gave

  甲基1- ø -mesyl -5- ö甲苯甲酰-β-d-psicofuranoside（5 -4,5-二- ;）从已知的合成1,3- ø异亚丙基-β-d-psicofuranose（1），其为制备脱水呋喃呋喃糖基核苷的关键碳水化合物前体。将5转化为乙酸7或溴化物10，然后（i）在SnCl 4存在下与全硅烷基化的N 6-苯甲酰腺嘌呤偶联，和（ii）用MeONa / MeOH处理得到1'，3'-脱水核苷9。在类似的反应顺序中使用甲硅烷基胸腺嘧啶可提供1'，4'-脱水核苷12。阻塞的反应11用NH 3 / MeOH洗脱，得到ø 2 1,1'-脱水核苷13，将其重新排列为12时的MeONa / MeOH中处理。脱保护后，将1'，3'-脱水糖15与甲硅烷基化的胸腺嘧啶缩合，得到1'，3'-脱水核苷16。