Carbonic acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 4-nitro-phenyl ester | 156939-39-8

• 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: Carbonic acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 4-nitro-phenyl ester
• 英文别名: [(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] (4-nitrophenyl) carbonate
• CAS: 156939-39-8
• 化学式: C₃₈H₃₅N₃O₁₁
• 分子量: 709.709
• InChiKey: XDTWJVVYWICJRQ-LBFZIJHGSA-N

物化性质

• 熔点：
  118-120 °C
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  52
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  168
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  Carbonic acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 4-nitro-phenyl ester 在 sodium dihydrogenphosphate 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 Phosphate-ON Phosphoramidite
  参考文献：
  名称：

  A novel reagent for the chemical phosphorylation of oligonucleotides

  摘要：

  A novel phosphoramidite reagent was developed to convert terminal hydroxyl groups of oligonucleotides into phosphate monoesters. The reagent's appearance as a solid foam is advantageous for its manipulation and handling in solid-phase synthesis and improves its thermal stability. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.10.167
• 作为产物：
  描述：

  对硝基苯基氯甲酸酯 、 保护胸苷 在 吡啶 作用下， 反应 20.0h， 生成 Carbonic acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 4-nitro-phenyl ester
  参考文献：
  名称：

  具有潜在反义应用的氨基甲酸酯锁核酸 (LNA) 寡核苷酸的合成和生物物理特性。

  摘要：

  反义寡核苷酸 (ASO) 正在成为治疗难治疾病的重要药物。对其 DNA 骨架的修饰对于抑制体内降解至关重要，但它们会降低与 RNA 靶标的结合亲和力。为了解决这个问题，我们将氨基甲酸酯 (CBM) DNA 骨架类似物的酶抗性与锁核酸糖 (LNA) 赋予的热力学稳定性相结合。使用二核苷酸亚磷酰胺策略和自动固相合成，我们合成了一组用多个 LNA-CBM 单元修饰的寡核苷酸。LNA 糖恢复与 RNA 目标的结合亲和力，在这方面，LNA 相对于 CBM 连接的位置很重要。含有氨基甲酸酯的寡核苷酸侧翼位于其 5' 和 3' LNA 的 -sides 与 RNA 形成稳定的双链体，与 DNA 形成不稳定的双链体，这对于反义应用来说是理想的。与单独的 LNA 或 CBM 骨架相比，氨基甲酸酯-LNA 修饰的寡核苷酸在蛇毒和胎牛血清的存在下也表现出更高的稳定性。

  DOI：

  10.1039/c9ob00691e

文献信息

• Novel phosphorylation reagents for improved processes to convert terminal hydroxyl groups of oligonucleotides into phosphate monoesters
  申请人：Proligo, LLC

  公开号：US20040230047A1

  公开（公告）日：2004-11-18

  The present invention discloses novel phosphoramidite reagents for use in oligonucleotide synthesis. The present invention further discloses novel methods for the conversion of terminal hydroxyl groups of oligonucleotides into phosphate monoesters. By employing novel reagents, as also disclosed herein, the methods are fully compatible with standard procedures for solid phase oligonucleotide synthesis and do not require additional processing steps. The inventive reagents to phosphorylate terminal hydroxyl groups of oligonucleotides are superior to the prior art in that they for the first time combine the desired attributes of being a solid compound for facile handling, comprising two &bgr;-eliminating protective groups removable as fast or faster than the standard cyanoethyl group, providing a DMT-group for easy monitoring of the coupling efficiency, and enabling a fast final deprotection of the phosphorylated oligonucleotide without any extra manipulation steps.

  本发明揭示了用于寡核苷酸合成的新型磷酰胺酯试剂。本发明进一步揭示了将寡核苷酸的末端羟基转化为磷酸单酯的新方法。通过采用本文中还披露的新型试剂，这些方法与固相寡核苷酸合成的标准程序完全兼容，不需要额外的处理步骤。本发明的试剂用于磷酸化寡核苷酸的末端羟基，优于先前的技术，因为它们首次结合了以下所需特性：作为固体化合物便于处理，包括两个可快速去除的β-消除保护基，这些基团的去除速度快于标准的氰乙基基团，提供一个DMT基团便于监测偶联效率，并且使磷酸化寡核苷酸的最终去保护过程快速进行，无需任何额外的操作步骤。
• Method for covalently attaching nucleosides and/or nucleotides on surfaces and method for determining coupling yields in the synthesis of nucleotides
  申请人：Stengele Klaus-Peter

  公开号：US20060154256A1

  公开（公告）日：2006-07-13

  The present invention relates to a method for covalently attaching nucleosides and/or nucleotides on surfaces having reactive functional groups, where in a first step, the reactive functional groups are made to react with suitable derivatized nucleosides and/or nucleotides, and in a second step, they are converted with a protecting group reagent, so that a reaction product of the consecutive reaction interacts with electromagnetic radiation such that it can be quantitatively determined. The invention also relates to a method for determining the repetitive coupling yields in the synthesis of nucleotides where the free 3′ or 5′ hydroxy group of a selected nucleoside and/or nucleotide is converted with a compound of formula (I) where L is a common suitable leaving group, the motif O—PX represents a phosphor amidite, a H-phosphonate a phosphonic acid ester, a phosphotriester, Y═O or S, N is a nucleoside or a nucleotide derivative which subsequently reacts further with a protecting group reagent and the elimination of the leaving group (L), which is subsequently further eliminated. The quantity of the leaving group (L) eliminated in step b) is quantitatively determined in the form of its anion (L − ) by means of optical spectroscopy.

  本发明涉及一种在具有反应性功能团的表面上共价连接核苷和/或核苷酸的方法。其中，在第一步中，反应性功能团与适当衍生的核苷和/或核苷酸发生反应，在第二步中，它们与保护基试剂转化，使得连续反应的反应产物与电磁辐射相互作用，从而可以定量测定。该发明还涉及一种确定核苷酸合成中重复偶联收率的方法，其中选择的核苷和/或核苷酸的自由3'或5'羟基转化为化合物(I)的形式，其中L是一种常见的适当离去基，O-PX基序列代表磷酰胺、H-膦酸酯、磷酸酯、磷酸三酯，Y=O或S，N是一个核苷或核苷酸衍生物，随后进一步与保护基试剂反应，并消除离去基(L)，随后进一步消除。步骤b)中消除的离去基(L)的数量以其阴离子(L-)的形式通过光谱学定量测定。
• Syntheses and binding studies of oligonucleotides containing N-hydroxycarbamate linkages: potential DNA cleaving antisense oligomers
  作者：Hui Li、Marvin J Miller

  DOI：10.1016/s0040-4039(00)00662-6

  日期：2000.6

  An efficient synthesis of N-hydroxycarbamate containing thymidine dimer 9 was accomplished and it was incorporated into automatic DNA syntheses to make thymidine 16mers T*-1, T*-2 and T*-3. Binding abilities of T*-1, T*-2 and T*-3 with poly (dA)-16mer were assayed by melting denaturation (Tm) studies of the corresponding duplexes. Iron binding ability of a thymidine oligomer with N-hydroxycarbamate linkages was studied by MALDI-MS. Nuclease stability assays showed that the modified oligonucleotides have enhanced resistance toward nuclease SI (endonuclease) compared to natural oligonucleotides. (C) 2000 Elsevier Science Ltd. All rights reserved.
• METHOD FOR COVALENTLY ATTACHING NUCLEOSIDES AND/OR NUCLEOTIDES ON SURFACES AND METHOD FOR DETERMINING COUPLING YIELDS IN THE SYNTHESIS OF NUCLEOTIDES
  申请人：Chemogenix GmbH

  公开号：EP1438322A2

  公开（公告）日：2004-07-21
• [EN] METHOD FOR COVALENTLY ATTACHING NUCLEOSIDES AND/OR NUCLEOTIDES ON SURFACES AND METHOD FOR DETERMINING COUPLING YIELDS IN THE SYNTHESIS OF NUCLEOTIDES<br/>[FR] PROCEDE DE FIXATION COVALENTE DE NUCLEOSIDES ET/OU NUCLEOTIDES SUR DES SURFACES, ET PROCEDE DE DETECTION DE RENDEMENTS DE COUPLAGE DANS LA SYNTHESE DE NUCLEOTIDES
  申请人：CHEMOGENIX GMBH

  公开号：WO2003035664A2

  公开（公告）日：2003-05-01

  The present invention relates to a method for covalently attaching nucleosides and/or nucleotides on surfaces having reactive functional groups, where in a first step, the reactive functional groups are made to react with suitable derivatized nucleosides and/or nucleotides, and in a second step, they are converted with a protecting group reagent, so that a reaction product of the consecutive reaction interacts with electromagnetic radiation such that it can be quantitatively determined. The invention also relates to a method for determining the repetitive coupling yields in the synthesis of nucleotides where the free 3' or 5' hydroxy group of a selected nucleoside and/or nucleotide is converted with a compound of formula (I), where L is a common suitable leaving group, the motif O-PX represents a phosphor amidite, a H-phosphonate a phosphonic acid ester, a phosphotriester, Y = O or S, N is a nucleoside or a nucleotide derivative which subsequently reacts further with a protecting group reagent and the elimination of the leaving group (L), which is subsequently further eliminated. The quantity of the leaving group (L) eliminated in step b) is quantitatively determined in the form of its anion (L-) by means of optical spectroscopy.