1-[(2R,4S,5R)-4-[[(3aS)-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]-5-methylpyrimidine-2,4-dione | 207125-21-1

• 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: 1-[(2R,4S,5R)-4-[[(3aS)-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]-5-methylpyrimidine-2,4-dione
• CAS: 207125-21-1；262861-73-4；1089723-30-7
• 化学式: C₃₆H₄₀N₃O₈P
• 分子量: 673.703
• InChiKey: CGOCKYCFUFGYTM-PUTLZPQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  48
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-[(2R,4S,5R)-4-[[(3aS)-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]-5-methylpyrimidine-2,4-dione 在 吡啶 、 双-[3-(三乙氧基硅)丙基]-四硫化物 、 benzimidazolium triflate 作用下， 以 乙腈 为溶剂， 反应 0.33h， 生成 (S)-N-acetyl-2-pyrrolidinylmethyl 5'-O-(p,p'-dimethoxytrityl)thymidin-3'-yl 3'-O-(tert-butyldimethylsilyl)thymidin-5'yl (S)-phosphorothioate
  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：

  L-脯氨醇 在 三乙胺 、 N,N-二异丙基乙胺 、 三氯化磷 作用下， 反应 18.0h， 生成 1-[(2R,4S,5R)-4-[[(3aS)-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]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  寡核苷酸硫代磷酸酯的固相立体选择性合成：核苷双环氧杂氮磷吡啶类化合物作为新的合成子

  摘要：

  衍生自L-或D-脯氨醇的核苷二环氧杂氮杂膦烷是一种新型合成子，具有固相立体选择性合成寡核苷硫代磷酸酯的潜力。

  DOI：

  10.1016/s0040-4039(98)00380-3

文献信息

• [EN] DIRECTED SYNTHESIS OF OLIGOPHOSPHORAMIDATE STEREOISOMERS<br/>[FR] SYNTHÈSE DIRIGÉE DE STÉRÉOISOMÈRES D'OLIGOPHOSPHORAMIDATES
  申请人：ROCHE DIAGNOSTICS GMBH

  公开号：WO2010060599A1

  公开（公告）日：2010-06-03

  The trivalent phosphorous atom of a compound is reacted with a reagent in such a manner that a stable phosphate mimetic or a specifier is formed. Phosphoramidites with a phosphorous atom containing at least one hydroxyl residue which is provided with a protective group are reacted for this purpose with a free hydroxyl group: In the first synthesis cycle the hydroxyl group is linked to a solid support via a cleavable or non-cleavable linker. In further synthesis cycles the hydroxyl group is created by cleavage of the protective group from the growing oligomer. This results in formation of a phosphorous acid triester which is reacted with azides. By selecting suitable monomers for the synthesis which have a defined stereoconformation compounds of Formula (1) are produced in a stereocontrolled manner.

  化合物中的三价磷原子与试剂反应，形成稳定的磷酸盐类似物或特异性物质。为此，具有至少一个含有保护基的氢氧基的含磷原子的磷酰胺酯与自由氢氧基反应：在第一个合成循环中，通过可裂解或不可裂解的连接剂将氢氧基与固体支持物连接。在进一步的合成循环中，通过从生长寡聚物中裂解保护基来创建氢氧基。这导致形成磷酸三酯，然后与叠氮化物反应。通过选择合适的单体进行合成，这些单体具有定义的立体构型，从而以立体控制的方式产生式（1）的化合物。
• 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.