Diisopropyl-phosphoramidous acid (2R,3R,4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-methoxy-5-(6-{[(4-methoxy-phenyl)-diphenyl-methyl]-amino}-purin-9-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester | 178422-02-1

• 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: Diisopropyl-phosphoramidous acid (2R,3R,4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-methoxy-5-(6-{[(4-methoxy-phenyl)-diphenyl-methyl]-amino}-purin-9-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester
• 英文别名: 3-[[(2R,3R,4R,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-methoxy-5-[6-[[(4-methoxyphenyl)-diphenylmethyl]amino]purin-9-yl]oxolan-3-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• CAS: 178422-02-1
• 化学式: C₆₁H₆₆N₇O₈P
• 分子量: 1056.21
• InChiKey: UATRLIQSKAIBDK-RXMWWASUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.5
• 重原子数：
  77
• 可旋转键数：
  24
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  157
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  Diisopropyl-phosphoramidous acid (2R,3R,4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-methoxy-5-(6-{[(4-methoxy-phenyl)-diphenyl-methyl]-amino}-purin-9-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester 、 [(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(3-benzoyl-2,4-dioxopyrimidin-1-yl)-2-(hydroxymethyl)-4-methoxyoxolan-3-yl]oxy-(2-cyanoethoxy)phosphoryl]oxymethyl]-4-benzoyloxy-5-[6-(dibenzoylamino)purin-9-yl]oxolan-3-yl] benzoate 在 四氮唑 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以86%的产率得到[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(3-benzoyl-2,4-dioxopyrimidin-1-yl)-2-[[[(2R,3R,4R,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-methoxy-5-[6-[[(4-methoxyphenyl)-diphenylmethyl]amino]purin-9-yl]oxolan-3-yl]oxy-(2-cyanoethoxy)phosphoryl]oxymethyl]-4-methoxyoxolan-3-yl]oxy-(2-cyanoethoxy)phosphoryl]oxymethyl]-4-benzoyloxy-5-[6-(dibenzoylamino)purin-9-yl]oxolan-3-yl] benzoate
  参考文献：
  名称：

  Chemical Synthesis of a 5‘-Terminal TMG-Capped Triribonucleotide m₃^2,2,7G^5‘pppAmpUmpA of U1 RNA

  摘要：

  The 5'-terminal TMG-capped triribonucleotide, m(3)(2,2,7)G(5')pppAmpUmpA, has been synthesized by condensation of an appropriately protected triribonucleotide derivative of ppAmpUmpA with a new TMG-capping reagent. During this total synthesis, it was found that the regioselective 2'-O-methylation of 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-N-(4-monomethoxytrityl)adenosine was achieved by use of MeI/Ag2O without affecting the base moiety. A new route to 2-N,2-N-dimethylguanosine from guanosine via a three-step reaction has also been developed by reductive methylation using paraformaldehyde and sodium cyanoborohydride. These key intermediates were used as starting materials for the construction of a fully protected derivative of pAmpUmpA and a TMG-capping reagent of Im-pm(3)(2,2,7)G. The target TMG-capped tetramer, m(3)(2,2,7)G(5')pppAmpUmpA, was synthesized by condensation of a partially protected triribonucleotide 5'-terminal diphosphate species, pp(AMMTr)mpUmpA, with Im-pm(3)(2,2,7)G followed by treatment with 80% acetic acid. The structure of m(3)(2,2,7)G(5')pppAmpUmpA was characterized by H-1 and P-31 NMR spectroscopy as well as enzymatic assay using snake venom phosphodiesterase, calf intestinal phosphatase, and nuclease P1.

  DOI：

  10.1021/jo952263v
• 作为产物：
  描述：

  (6aR,8R,9R,9aS)-8-[6-[[(4-methoxyphenyl)-diphenylmethyl]amino]purin-9-yl]-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-9-ol 在 potassium fluoride 、 四乙基溴化铵 、 水 、 N,N-二异丙基乙胺 、 silver(l) oxide 作用下， 以 吡啶 、 二氯甲烷 、 乙腈 为溶剂， 反应 23.0h， 生成 Diisopropyl-phosphoramidous acid (2R,3R,4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-methoxy-5-(6-{[(4-methoxy-phenyl)-diphenyl-methyl]-amino}-purin-9-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester
  参考文献：
  名称：

  Chemical Synthesis of a 5‘-Terminal TMG-Capped Triribonucleotide m₃^2,2,7G^5‘pppAmpUmpA of U1 RNA

  摘要：

  The 5'-terminal TMG-capped triribonucleotide, m(3)(2,2,7)G(5')pppAmpUmpA, has been synthesized by condensation of an appropriately protected triribonucleotide derivative of ppAmpUmpA with a new TMG-capping reagent. During this total synthesis, it was found that the regioselective 2'-O-methylation of 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-N-(4-monomethoxytrityl)adenosine was achieved by use of MeI/Ag2O without affecting the base moiety. A new route to 2-N,2-N-dimethylguanosine from guanosine via a three-step reaction has also been developed by reductive methylation using paraformaldehyde and sodium cyanoborohydride. These key intermediates were used as starting materials for the construction of a fully protected derivative of pAmpUmpA and a TMG-capping reagent of Im-pm(3)(2,2,7)G. The target TMG-capped tetramer, m(3)(2,2,7)G(5')pppAmpUmpA, was synthesized by condensation of a partially protected triribonucleotide 5'-terminal diphosphate species, pp(AMMTr)mpUmpA, with Im-pm(3)(2,2,7)G followed by treatment with 80% acetic acid. The structure of m(3)(2,2,7)G(5')pppAmpUmpA was characterized by H-1 and P-31 NMR spectroscopy as well as enzymatic assay using snake venom phosphodiesterase, calf intestinal phosphatase, and nuclease P1.

  DOI：

  10.1021/jo952263v

文献信息

• Chemical Synthesis of a 5‘-Terminal TMG-Capped Triribonucleotide m₃^2,2,7G⁵^‘pppAmpUmpA of U1 RNA
  作者：Mitsuo Sekine、Michinori Kadokura、Takahiko Satoh、Kohji Seio、Takeshi Wada、Utz Fischer、Vicki Sumpter、Reinhard Lührmann

  DOI：10.1021/jo952263v

  日期：1996.1.1

  The 5'-terminal TMG-capped triribonucleotide, m(3)(2,2,7)G(5')pppAmpUmpA, has been synthesized by condensation of an appropriately protected triribonucleotide derivative of ppAmpUmpA with a new TMG-capping reagent. During this total synthesis, it was found that the regioselective 2'-O-methylation of 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-N-(4-monomethoxytrityl)adenosine was achieved by use of MeI/Ag2O without affecting the base moiety. A new route to 2-N,2-N-dimethylguanosine from guanosine via a three-step reaction has also been developed by reductive methylation using paraformaldehyde and sodium cyanoborohydride. These key intermediates were used as starting materials for the construction of a fully protected derivative of pAmpUmpA and a TMG-capping reagent of Im-pm(3)(2,2,7)G. The target TMG-capped tetramer, m(3)(2,2,7)G(5')pppAmpUmpA, was synthesized by condensation of a partially protected triribonucleotide 5'-terminal diphosphate species, pp(AMMTr)mpUmpA, with Im-pm(3)(2,2,7)G followed by treatment with 80% acetic acid. The structure of m(3)(2,2,7)G(5')pppAmpUmpA was characterized by H-1 and P-31 NMR spectroscopy as well as enzymatic assay using snake venom phosphodiesterase, calf intestinal phosphatase, and nuclease P1.