(Z)-1-[3-(dimethoxytrityloxy)-2-[2-cyanoethoxy(diisopropylamino)phosphinoxy-methyl]prop-1-enyl]thymine | 549533-93-9

• 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: (Z)-1-[3-(dimethoxytrityloxy)-2-[2-cyanoethoxy(diisopropylamino)phosphinoxy-methyl]prop-1-enyl]thymine
• 英文别名: 3-[[(Z)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-(5-methyl-2,4-dioxopyrimidin-1-yl)prop-2-enoxy]-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• CAS: 549533-93-9
• 化学式: C₃₉H₄₇N₄O₇P
• 分子量: 714.799
• InChiKey: JIKIDTBCIIAROD-GDWJVWIDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  51
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (E)-1-[2-(dimethoxytrityloxymethyl)-3-hydroxyprop-1-enyl]thymine 、 (Z)-1-[3-(dimethoxytrityloxy)-2-[2-cyanoethoxy(diisopropylamino)phosphinoxy-methyl]prop-1-enyl]thymine 在 四氮唑 作用下， 生成 2-cyanoethyl bis-[(E)-2-(dimethoxytrityloxymethyl)-3-(1-thyminyl)prop-2-enyl] phosphite
  参考文献：
  名称：

  Improved synthesis of oligonucleotides with an allylic backbone. Oligonucleotides containing acyclic, achiral nucleoside analogues: N-1 or N-9-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]nucleobases

  摘要：

  描述了一种改进的磷酰胺法，用于制备用非环状、无手性的单体1修饰的寡核苷酸。对在固相或溶液中制备的二聚体的研究表明，含有烯丙基单元1的磷三酯二聚体对碱不稳定，而磷二酯二聚体则稳定。通过用磷酰胺基团3替换氰乙基磷酰胺基团2，可以获得磷二酯二聚体，后者在氧化后可直接生成。发现磷二酯二聚体对封闭和氧化稳定，但对酸有一定的敏感性。通过减少去三苷化过程中与酸的接触时间，可以制备含有4或8个修饰的A、G或T单位的寡核苷酸。这些修饰过的寡核苷酸能够与互补的DNA和RNA结合，但亲和力有所降低（每次修饰导致的ΔTm为−1到−5 °C）。

  DOI：

  10.1039/b517504f
• 作为产物：
  描述：

  1-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]thymine 在 吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 (Z)-1-[3-(dimethoxytrityloxy)-2-[2-cyanoethoxy(diisopropylamino)phosphinoxy-methyl]prop-1-enyl]thymine
  参考文献：
  名称：

  Improved synthesis of oligonucleotides with an allylic backbone. Oligonucleotides containing acyclic, achiral nucleoside analogues: N-1 or N-9-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]nucleobases

  摘要：

  描述了一种改进的磷酰胺法，用于制备用非环状、无手性的单体1修饰的寡核苷酸。对在固相或溶液中制备的二聚体的研究表明，含有烯丙基单元1的磷三酯二聚体对碱不稳定，而磷二酯二聚体则稳定。通过用磷酰胺基团3替换氰乙基磷酰胺基团2，可以获得磷二酯二聚体，后者在氧化后可直接生成。发现磷二酯二聚体对封闭和氧化稳定，但对酸有一定的敏感性。通过减少去三苷化过程中与酸的接触时间，可以制备含有4或8个修饰的A、G或T单位的寡核苷酸。这些修饰过的寡核苷酸能够与互补的DNA和RNA结合，但亲和力有所降低（每次修饰导致的ΔTm为−1到−5 °C）。

  DOI：

  10.1039/b517504f

文献信息

• Preparation and Properties of a New Type of Acyclic, Achiral Nucleoside Analogue
  作者：Thomas Boesen、Daniel Sejer Pedersen、Jacob Jensen、Michael T. Munck、Brian M. Nielsen、Asger B. Petersen、Ulla Henriksen、Britta M. Dahl、Otto Dahl

  DOI：10.1081/ncn-120021967

  日期：2003.10

  Preparation of the nucleoside analogues 1 and incorporation of 1, B = T, in deoxyribooligonucleotides by the phosphoramidite method is described. A two-step deprotection procedure was developed to reduce cleavage of the modified allylic unit. The binding properties of the modified oligonucleotides towards complementary DNA and RNA has been evaluated by Tm measurements showing a deltaTm of -2 to -6

  描述了通过亚磷酰胺方法在脱氧核糖寡核苷酸中制备核苷类似物1和掺入1，B ＝ T。开发了两步脱保护程序以减少修饰的烯丙基单元的裂解。已通过Tm测量评估了修饰的寡核苷酸对互补DNA和RNA的结合特性，显示出每次修饰的ΔTm为-2至-6.5℃。在3'-末端具有两个修饰的寡核苷酸显示出对3'-核酸外切酶切割的抗性。对于1，B = G或T或任何三羟基衍生物5，未发现针对HIV-1或HSV-1的抗病毒活性。
• Oligonucleotides containing a new type of acyclic, achiral nucleoside analogue: 1-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]thymine
  作者：Thomas Boesen、Daniel Sejer Pedersen、Brian M. Nielsen、Asger B. Petersen、Ulla Henriksen、Britta M. Dahl、Otto Dahl

  DOI：10.1016/s0960-894x(03)00008-8

  日期：2003.3

  An achiral, acyclic nucleoside analogue has been incorporated once or twice in oligodeoxyribonucleotides by the phosphoramidite method, and conditions found which allow deprotection of the oligonucleotides containing a sensitive modified allylic unit. The binding affinity of the modified oligonucleotides towards complementary DNA and RNA was reduced compared to unmodified DNA (DeltaT(m) -2 to -6.5degreesC). An oligonucleotide with two modifications at the 3'-end showed considerable resistance towards cleavage with a 3'-exonuclease. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Improved synthesis of oligonucleotides with an allylic backbone. Oligonucleotides containing acyclic, achiral nucleoside analogues: N-1 or N-9-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]nucleobases
  作者：Britta M. Dahl、Ulla Henriksen、Otto Dahl

  DOI：10.1039/b517504f

  日期：——

  An improved phosphoramidite method is described to prepare oligonucleotides modified with the acyclic, achiral monomers 1. Examination of dimers, prepared on solid support or in solution, showed that phosphortriester dimers containing the allylic unit 1 were unstable towards bases, whereas phosphordiester dimers were stable. Phosphordiester dimers were obtained by replacing cyanoethyl phosphoramidites 2 with phosphoramidites 3, which gave phosphordiesters directly upon oxidation. The phosphordiester dimers were found to be stable towards capping and oxidation, but were somewhat labile towards acids. By reducing the contact time to acids during detritylation it was possible to prepare oligonucleotides containing 4 or 8 modified A, G or T units. The modified oligonucleotides hybridized to complementary DNA and RNA, although with reduced affinity (ΔTm per modification −1 to −5 °C).

  描述了一种改进的磷酰胺法，用于制备用非环状、无手性的单体1修饰的寡核苷酸。对在固相或溶液中制备的二聚体的研究表明，含有烯丙基单元1的磷三酯二聚体对碱不稳定，而磷二酯二聚体则稳定。通过用磷酰胺基团3替换氰乙基磷酰胺基团2，可以获得磷二酯二聚体，后者在氧化后可直接生成。发现磷二酯二聚体对封闭和氧化稳定，但对酸有一定的敏感性。通过减少去三苷化过程中与酸的接触时间，可以制备含有4或8个修饰的A、G或T单位的寡核苷酸。这些修饰过的寡核苷酸能够与互补的DNA和RNA结合，但亲和力有所降低（每次修饰导致的ΔTm为−1到−5 °C）。