N-[1-[(2R,4S,5R)-4-[[(3aR)-3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaphosphol-1-yl]oxy]-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]oxolan-2-yl]-2-oxopyrimidin-4-yl]benzamide | 876152-60-2

• 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: N-[1-[(2R,4S,5R)-4-[[(3aR)-3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaphosphol-1-yl]oxy]-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]oxolan-2-yl]-2-oxopyrimidin-4-yl]benzamide
• CAS: 876152-60-2
• 化学式: C₄₂H₄₃N₄O₈P
• 分子量: 762.799
• InChiKey: DCBFTZWPEVDMKU-HZCKNRRTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  55
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[1-[(2R,4S,5R)-4-[[(3aR)-3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaphosphol-1-yl]oxy]-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]oxolan-2-yl]-2-oxopyrimidin-4-yl]benzamide 在 吡啶 、 benzimidazolium triflate 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  三氟甲磺酸唑作为促进核苷亚磷酰胺和核苷缩合的促进剂在 Agrawal 立体选择性合成核苷硫代磷酸酯中的效用

  摘要：

  本文证明了一些唑鎓三氟甲磺酸盐，如 N-苯基咪唑鎓三氟甲磺酸盐、苯并咪唑鎓三氟甲磺酸盐和 N-甲基苯并咪唑三氟甲磺酸盐，作为促进 5'-O 核苷和立体化学纯 5 立体选择性缩合的促进剂，比 1H-四唑更有用。 '-O-(p,p'-二甲氧基三苯甲基)-3'-O-{(4R)-1H,3H-吡咯并[1,2-c]-1,3,2-氧氮杂磷脂}-2-基2' -脱氧核糖核苷 (Rc-1) 或 5'-O-(p,p'-二甲氧基三苯甲基)-3'-O-{(4S)-1H,3H-吡咯并[1,2-c]-1,3,2 -oxazaphospholidin}-2-yl 2'-脱氧核糖核苷 (Sc-2)（Agrawal 策略）。唑鎓三氟甲磺酸盐允许通过使用立体化学纯的亚磷酰胺通过上述缩合立体选择性地形成核苷酸间硫代磷酸酯键，然后使用双[3-三乙氧基甲硅烷基丙基]四硫化物进行硫化。在使用合适的三氟甲磺酸唑鎓盐（如苯并咪唑鎓三氟甲磺酸盐、N-甲基苯并咪唑鎓三氟甲磺酸盐或

  DOI：

  10.1002/ejoc.200500403
• 作为产物：
  描述：

  N4-苯甲酰基-5′-O-(4,4′-二甲氧基三苯基)-2′-脱氧胞苷 、 (3aR)-1-chlorotetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaphosphole 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-[1-[(2R,4S,5R)-4-[[(3aR)-3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaphosphol-1-yl]oxy]-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]oxolan-2-yl]-2-oxopyrimidin-4-yl]benzamide
  参考文献：
  名称：

  Stereo-enriched phosphorothioate oligodeoxynucleotides: synthesis, biophysical and biological properties

  摘要：

  Stereo-enriched [Rp] and [Sp]-phosphorothioate oligodeoxynucleotides are synthesized using oxazaphospholidine derivatized monomers. Three different designs of phosphorothioate oligodeoxynucleotides (PS-oligos), (i) stereo-enriched all-[Rp] or all-[Sp] PS-linkages, (ii) stereo-random mixture of PS-linkages, and (iii) segments containing certain number of stereo-enriched [Rp] and [Sp] PS-linkages ([Sp-Rp-Sp] or [Rp-Sp-Rp]), have been studied. Thermal melting studies of these PS-oligos with RNA complementary strands showed that the binding affinities are in the order [Rp] > [Sp-Rp-Sp] = [Rp-Sp-Rp] > stereo-random > [Sp]. Circular dichroism (CD) studies suggest that the stereochemistry of the PS-oligo does not affect the global conformation of the duplex. The in vitro nuclease stability of these PS-oligos is in the order [Sp] > [Sp-Rp-Sp], stereo-random > [Rp]. The RNase H activation is in the order [Rp] > stereo-random > [Rp-Sp-Rp] > [Sp] > [Sp-Rp-Sp]. Studies in a cancer cell Line of PS-oligos targeted to MDM2 mRNA showed that all oligos had similar biological activity under the experimental conditions employed. Protein- and enzyme-binding studies showed insignificant stereo-dependent binding to proteins. The [Sp] and [Sp-Rp-Sp] chimeric and stereo-random PS-oligos that contained a CpG motif showed higher cell proliferation than [Rp] PS-oligo of the same sequence. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00275-8

文献信息

• Stereo-enriched phosphorothioate oligodeoxynucleotides: synthesis, biophysical and biological properties
  作者：Dong Yu、Ekambar R. Kandimalla、Allysen Roskey、Qiuyan Zhao、Lihong Chen、Jiangdong Chen、Sudhir Agrawal

  DOI：10.1016/s0968-0896(99)00275-8

  日期：2000.1

  Stereo-enriched [Rp] and [Sp]-phosphorothioate oligodeoxynucleotides are synthesized using oxazaphospholidine derivatized monomers. Three different designs of phosphorothioate oligodeoxynucleotides (PS-oligos), (i) stereo-enriched all-[Rp] or all-[Sp] PS-linkages, (ii) stereo-random mixture of PS-linkages, and (iii) segments containing certain number of stereo-enriched [Rp] and [Sp] PS-linkages ([Sp-Rp-Sp] or [Rp-Sp-Rp]), have been studied. Thermal melting studies of these PS-oligos with RNA complementary strands showed that the binding affinities are in the order [Rp] > [Sp-Rp-Sp] = [Rp-Sp-Rp] > stereo-random > [Sp]. Circular dichroism (CD) studies suggest that the stereochemistry of the PS-oligo does not affect the global conformation of the duplex. The in vitro nuclease stability of these PS-oligos is in the order [Sp] > [Sp-Rp-Sp], stereo-random > [Rp]. The RNase H activation is in the order [Rp] > stereo-random > [Rp-Sp-Rp] > [Sp] > [Sp-Rp-Sp]. Studies in a cancer cell Line of PS-oligos targeted to MDM2 mRNA showed that all oligos had similar biological activity under the experimental conditions employed. Protein- and enzyme-binding studies showed insignificant stereo-dependent binding to proteins. The [Sp] and [Sp-Rp-Sp] chimeric and stereo-random PS-oligos that contained a CpG motif showed higher cell proliferation than [Rp] PS-oligo of the same sequence. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Utility of Azolium Triflates as Promoters for the Condensation of a Nucleoside Phosphoramidite and a Nucleoside in the Agrawal's Stereoselective Synthesis of Nucleoside Phosphorothioates
  作者：Mamoru Hyodo、Hirotaka Ando、Hisashi Nishitani、Akira Hattori、Hiroyuki Hayakawa、Masanori Kataoka、Yoshihiro Hayakawa

  DOI：10.1002/ejoc.200500403

  日期：2005.12

  allowed the stereoselective formation of an internucleotide phosphorothioate bond via the above-described condensation using a stereochemically pure phosphoramidite, followed by sulfurization using bis[3-triethoxysilylpropyl]tetrasulfide. The highest diastereoexcess values of the products in the synthesis of dideoxyribonucleoside phosphorothioates using a suitable azolium triflate such as benzimidazolium

  本文证明了一些唑鎓三氟甲磺酸盐，如 N-苯基咪唑鎓三氟甲磺酸盐、苯并咪唑鎓三氟甲磺酸盐和 N-甲基苯并咪唑三氟甲磺酸盐，作为促进 5'-O 核苷和立体化学纯 5 立体选择性缩合的促进剂，比 1H-四唑更有用。 '-O-(p,p'-二甲氧基三苯甲基)-3'-O-(4R)-1H,3H-吡咯并[1,2-c]-1,3,2-氧氮杂磷脂}-2-基2' -脱氧核糖核苷 (Rc-1) 或 5'-O-(p,p'-二甲氧基三苯甲基)-3'-O-(4S)-1H,3H-吡咯并[1,2-c]-1,3,2 -oxazaphospholidin}-2-yl 2'-脱氧核糖核苷 (Sc-2)（Agrawal 策略）。唑鎓三氟甲磺酸盐允许通过使用立体化学纯的亚磷酰胺通过上述缩合立体选择性地形成核苷酸间硫代磷酸酯键，然后使用双[3-三乙氧基甲硅烷基丙基]四硫化物进行硫化。在使用合适的三氟甲磺酸唑鎓盐（如苯并咪唑鎓三氟甲磺酸盐、N-甲基苯并咪唑鎓三氟甲磺酸盐或