2'-O-bis[(2-cyano-1,1-dimethylethoxy)thiophosphoryl]-N³-benzoyl-5'-O-(4,4'-dimethoxytrityl)uridine 3'-(2-cyanoethyl-N,N-diisopropylphosphoramidite) | 176664-16-7

• 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: 2'-O-bis[(2-cyano-1,1-dimethylethoxy)thiophosphoryl]-N³-benzoyl-5'-O-(4,4'-dimethoxytrityl)uridine 3'-(2-cyanoethyl-N,N-diisopropylphosphoramidite)
• 英文别名: 3-[[(2R,3R,4R,5R)-2-(3-benzoyl-2,4-dioxopyrimidin-1-yl)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxyoxolan-3-yl]oxy-(1-cyano-2-methylpropan-2-yl)oxyphosphinothioyl]oxy-3-methylbutanenitrile
• CAS: 176664-16-7
• 化学式: C₅₆H₆₆N₆O₁₂P₂S
• 分子量: 1109.19
• InChiKey: SIPQQKALNMGLFX-KWJCMQTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  77
• 可旋转键数：
  26
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  248
• 氢给体数：
  0
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  N6-二苯甲酰基腺苷-2',3'-二苯甲酸酯 、 2'-O-bis[(2-cyano-1,1-dimethylethoxy)thiophosphoryl]-N³-benzoyl-5'-O-(4,4'-dimethoxytrityl)uridine 3'-(2-cyanoethyl-N,N-diisopropylphosphoramidite) 在 吡啶 、 四氮唑 、 水 、 碘 作用下， 生成 [(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(3-benzoyl-2,4-dioxopyrimidin-1-yl)-4-bis[(1-cyano-2-methylpropan-2-yl)oxy]phosphinothioyloxy-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]oxolan-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：

  Kinetics and Mechanism of Facile and Selective Dephosphorylation of 2‘-Phosphorylated and 2‘-Thiophosphorylated Dinucleotides:  Neighboring 3‘−5‘ Phosphodiester Promotes 2‘-Dephosphorylation

  摘要：

  2'-phosphorylated and 2'-thiophosphorylated dinucleotides U(2'-p)pU (1) and U(2'-ps)pU (2) were found to undergo facile 2'-specific dephosphorylation at 90 degrees C in neutral aqueous solution to give UpU, and the first-order rate constants of these reactions were determined by HPLC. Particularly, U(2'-ps)pU (2, k = 1.38 +/- 0.4 x 10(-3) s(-1), t(comp) = 1 h) was cleanly dephosphorylated ca. 100 times more rapidly than U(2'-p)pU (1, k = 1.41 +/- 0.05 x 10(-5) s(-1), t(comp) = 72 h). Dephosphorylations of 1 and 2 were faster than those of thymidine 3'-phosphate (8) and thymidine 3'-thiophosphate (9), respectively. The kinetic data observed were independent of the 2'- or 3'-position of the phosphate group and the kind of base moiety. The neighboring 3'-5' phosphodiester function most probably promotes the 2'-dephosphorylation efficiently. A branched trimer, U(2'-pU)pU (3), and related compounds having a substituent on the 2'-phosphoryl group, such as U(2'-pp-biotin)pU (4) and U(2'-ps-bimane)pU (5), were rather resistant to hydrolysis. The addition of divalent metal ions (Mg2+, Mn2+, Zn2+, Ca2+, Co2+, and Cd2+) remarkably decreased the rate of 2'-de(thio)phosphorylation of 1 or 2. Among these metal ions, Zn2+ most significantly inhibited the dephosphorylation. On the contrary, trivalent metal ions considerably accelerated the 2'-de(thio)phosphorylation of 1 or 2. The mechanism of 2'-dephosphorylation in the presence and absence of various metal ions is also discussed.

  DOI：

  10.1021/jo970021k
• 作为产物：
  描述：

  3-羟基-3-甲基丁腈 在 吡啶 、 四氮唑 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 (HF)x*Py 、 三乙胺 作用下， 以 四氢呋喃 、 吡啶 、 乙醚 、 二氯甲烷 为溶剂， 反应 11.42h， 生成 2'-O-bis[(2-cyano-1,1-dimethylethoxy)thiophosphoryl]-N³-benzoyl-5'-O-(4,4'-dimethoxytrityl)uridine 3'-(2-cyanoethyl-N,N-diisopropylphosphoramidite)
  参考文献：
  名称：

  2'-磷酸化尿苷衍生物中2'-3'磷酸迁移的立体和电子控制及其在2'-磷酸化低聚水杨酸酯合成中的应用研究。

  摘要：

  对于通过使用新的亚磷酰胺结构单元合成2'-磷酸化的低聚吡啶二酸酯，已经研究了几种掩蔽的磷酰基作为2'-磷酸酯前体，当3'羟基保护基必须是3'羟基时，不应将其迁移到3'位置。去除亚磷酰胺残基，将其引入3'-位。结果，发现双（2-氰基-1,1-二甲基乙氧基）硫代磷酰基（BCMETP）是最合适的2'-磷酸盐前体。该硫代磷酰基可通过与双（2-氰基-1，1-二甲基乙氧基）（二乙氨基）膦进行磷酸化，然后硫化而引入3'，5'-甲硅烷基化尿苷衍生物7的2'-羟基。用（HF）（x）（）。Py在THF中处理2'-硫代磷酸化产物15，仅得到3'，5' -未保护的尿苷衍生物16a。化合物16a通过两步反应被转化为亚磷酰胺单元22。该构件用于U（2'-p）pU（29）和U（2'-ps）pU（30）的溶液相合成。通过在N，O-双（三甲基甲硅烷基）乙酰胺（BSA）存在下用DBU处理，从完全保护的衍生物25中有效除去2-

  DOI：

  10.1021/jo952073k

文献信息

• Studies on Steric and Electronic Control of 2‘−3‘ Phosphoryl Migration in 2‘-Phosphorylated Uridine Derivatives and Its Application to the Synthesis of 2‘-Phosphorylated Oligouridylates
  作者：Mitsuo Sekine、Hiroyuki Tsuruoka、Shin Iimura、Hiroshi Kusuoku、Takeshi Wada、Kiyotaka Furusawa

  DOI：10.1021/jo952073k

  日期：1996.1.1

  phosphitylation with bis(2-cyano-1,1-dimethylethoxy)(diethylamino)phosphine followed by sulfurization. Treatment of the 2'-thiophosphorylated product 15 with (HF)(x)().Py in THF gave exclusively the 3',5'-unprotected uridine derivative 16a. Compound 16a was converted to the phosphoramidite unit 22 via a two-step reaction. This building block was used for the solution phase synthesis of U(2'-p)pU (29)

  对于通过使用新的亚磷酰胺结构单元合成2'-磷酸化的低聚吡啶二酸酯，已经研究了几种掩蔽的磷酰基作为2'-磷酸酯前体，当3'羟基保护基必须是3'羟基时，不应将其迁移到3'位置。去除亚磷酰胺残基，将其引入3'-位。结果，发现双（2-氰基-1,1-二甲基乙氧基）硫代磷酰基（BCMETP）是最合适的2'-磷酸盐前体。该硫代磷酰基可通过与双（2-氰基-1，1-二甲基乙氧基）（二乙氨基）膦进行磷酸化，然后硫化而引入3'，5'-甲硅烷基化尿苷衍生物7的2'-羟基。用（HF）（x）（）。Py在THF中处理2'-硫代磷酸化产物15，仅得到3'，5' -未保护的尿苷衍生物16a。化合物16a通过两步反应被转化为亚磷酰胺单元22。该构件用于U（2'-p）pU（29）和U（2'-ps）pU（30）的溶液相合成。通过在N，O-双（三甲基甲硅烷基）乙酰胺（BSA）存在下用DBU处理，从完全保护的衍生物25中有效除去2-
• Kinetics and Mechanism of Facile and Selective Dephosphorylation of 2‘-Phosphorylated and 2‘-Thiophosphorylated Dinucleotides:  Neighboring 3‘−5‘ Phosphodiester Promotes 2‘-Dephosphorylation
  作者：Hiroyuki Tsuruoka、Koh-ichiroh Shohda、Takeshi Wada、Mitsuo Sekine

  DOI：10.1021/jo970021k

  日期：1997.5.1

  2'-phosphorylated and 2'-thiophosphorylated dinucleotides U(2'-p)pU (1) and U(2'-ps)pU (2) were found to undergo facile 2'-specific dephosphorylation at 90 degrees C in neutral aqueous solution to give UpU, and the first-order rate constants of these reactions were determined by HPLC. Particularly, U(2'-ps)pU (2, k = 1.38 +/- 0.4 x 10(-3) s(-1), t(comp) = 1 h) was cleanly dephosphorylated ca. 100 times more rapidly than U(2'-p)pU (1, k = 1.41 +/- 0.05 x 10(-5) s(-1), t(comp) = 72 h). Dephosphorylations of 1 and 2 were faster than those of thymidine 3'-phosphate (8) and thymidine 3'-thiophosphate (9), respectively. The kinetic data observed were independent of the 2'- or 3'-position of the phosphate group and the kind of base moiety. The neighboring 3'-5' phosphodiester function most probably promotes the 2'-dephosphorylation efficiently. A branched trimer, U(2'-pU)pU (3), and related compounds having a substituent on the 2'-phosphoryl group, such as U(2'-pp-biotin)pU (4) and U(2'-ps-bimane)pU (5), were rather resistant to hydrolysis. The addition of divalent metal ions (Mg2+, Mn2+, Zn2+, Ca2+, Co2+, and Cd2+) remarkably decreased the rate of 2'-de(thio)phosphorylation of 1 or 2. Among these metal ions, Zn2+ most significantly inhibited the dephosphorylation. On the contrary, trivalent metal ions considerably accelerated the 2'-de(thio)phosphorylation of 1 or 2. The mechanism of 2'-dephosphorylation in the presence and absence of various metal ions is also discussed.