N⁴-{[4-(tert-butyl)phenoxy]acetyl}-2'-deoxy-5'-O-(4,4'-dimethoxytrityl)cytidine | 149989-44-6

• 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: N⁴-{[4-(tert-butyl)phenoxy]acetyl}-2'-deoxy-5'-O-(4,4'-dimethoxytrityl)cytidine
• 英文别名: 5'-dimethoxytrityl-N⁴-(4-tert-butylphenoxyacetyl) deoxycytidine；N-[1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-2-oxopyrimidin-4-yl]-2-(4-tert-butylphenoxy)acetamide
• CAS: 149989-44-6
• 化学式: C₄₂H₄₅N₃O₈
• 分子量: 719.835
• InChiKey: VKBVJIVLVSSLLF-RETAKORUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  53
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N⁴-{[4-(tert-butyl)phenoxy]acetyl}-2'-deoxy-5'-O-(4,4'-dimethoxytrityl)cytidine 在 N,N-二异丙基乙胺 、 5-(乙硫基)-1H-四唑 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Solid-Phase Synthesis, Hybridizing Ability, Uptake, and Nuclease Resistant Profiles of Position-Selective Cationic and Hydrophobic Phosphotriester Oligonucleotides

  摘要：

  Analogues of oligonucleotides and mononucleotides with hydrophobic and/or cationic phophotriester functionalities often generate an improvement in target affinity and cellular uptake. Here we report the synthesis of phosphotriester oligodeoxyribonucleotides (ODNs) that are stable to the conditions used for their preparation. The method has been demonstrated by introducing phosphoramidite synthons where N-benzyloxycarbonyl (Z) protected amino alcohols replace the cyanoethyl group. After synthesis these ODNs were found to be stable to the condition required to remove base labile protecting groups and the ODNs from the solid support. Moreover the use of 1-(4,4-dimethyl-2, 6-dioxocyclohex-1-ylidene) ethyl (Dde) in place of Z protection on the amino alcohol has allowed us to introduce cationic aminoethyl phosphotriester modifications into ODNs. Melting temperatures of duplexes containing cationic or hydrophobic Z modified ODNs indicate that the backbone-phosphotriester modifications minimally affect duplex stability. Nuclease stability assays demonstrate that these phosphotriesters are resistant toward 5'- and 3'-exonudeases. Fluorescently labeled 23-mer ODNs modified with four cationic or hydrophobic Z phosphotriester linkages show efficient cellular uptake during passive transfection in HeLa and Jurkat cells.

  DOI：

  10.1021/acs.joc.5b01512
• 作为产物：
  描述：

  在 potassium fluoride 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以72%的产率得到N⁴-{[4-(tert-butyl)phenoxy]acetyl}-2'-deoxy-5'-O-(4,4'-dimethoxytrityl)cytidine
  参考文献：
  名称：

  Facile methods to recycle nucleosides during solid phase synthesis of oligonucleotides

  摘要：

  Solid phase syntheses of oligonucleotides, using nucleoside phosphoramidites or methylphosphonamidites require a large excess of nucleoside monomers over the hydroxy functions of the growing oligonucleotide chain bound onto the solid phase. The outlined method allows to recover the excess nucleosides. All the protective groups on the sugar and the nucleobase of the monomers are maintained throughout the recycling process.

  DOI：

  10.1016/s0040-4039(00)76822-5

文献信息

• Alkynyl Phosphonate DNA: A Versatile “Click”able Backbone for DNA-Based Biological Applications
  作者：Heera Krishna、Marvin H. Caruthers

  DOI：10.1021/ja3026714

  日期：2012.7.18

  is useful for introducing additional functionality, the triazolylphosphonate, and present preliminary data on its biological properties. We have developed a new phosphoramidite synthon--the alkynyl phosphinoamidite, which is compatible with conventional solid-phase oligonucleotide synthesis. Postsynthesis, the alkynylphosphonate can be functionalized via "Click" chemistry to generate the 1,2,3-triazolyl

  与基于 DNA 的生物应用相关的主要障碍包括靶向细胞递送、不良的非特异性效应、与各种类似物或用于将寡核苷酸递送至细胞的试剂相关的毒性以及对细胞内酶的稳定性。尽管已经研究了大量不同的类似物，但尚未开发出一种可以系统地解决这些挑战的通用方法。在这篇文章中，我们提出了一种新的、可点击的、多功能的化学物质，可用于快速引入用于研究这些不同问题的多种功能。作为该方法的演示，我们合成了核心类似物，可用于引入额外的功能，三唑基膦酸酯，并提供其生物学特性的初步数据。我们开发了一种新的亚磷酰胺合成子——炔基亚磷酰胺，它与传统的固相寡核苷酸合成兼容。合成后，炔基膦酸酯可通过“点击”化学功能化以生成 1,2,3-三唑基或取代的 1,2,3-三唑基膦酸酯-2'-脱氧核糖核苷酸核苷酸间键。本手稿描述了具有 1,2,3-三唑基膦酸酯 (TP) 以及磷酸或硫代磷酸酯核苷酸间连接以及 2'-OMe 核糖核苷酸和锁核酸 (LNA)
• 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。
• Synthesis of Photolabile 5′-O-Phosphoramidites for the Photolithographic Production of Microarrays of Inversely Oriented Oligonucleotides
  作者：Markus Beier、Achim Stephan、Jörg D. Hoheisel

  DOI：10.1002/1522-2675(20010711)84:7<2089::aid-hlca2089>3.0.co;2-0

  日期：2001.7.11

  The photolabile 3 ' -O-[2-(2-nitrophenyl)propoxy]carbonyl}-protected 5 ' -phosphoramidites (16-18) were synthesized (see Scheme) for an alternative mode of light-directed production of oligonucleotide arrays. Because of the characteristics of these monomeric building blocks, photolithographic in situ DNA synthesis occurred in 5 ' --> 3 ' direction, in agreement with the orientation of enzymatic synthesis. Synthesis yields were as good as those of conventional reactions. The resulting oligonucleotides are attached to the: surface via their 5 ' -termini, while the 3 ' -hydroxy groups are available as substrates for enzymatic reactions such as primer extension upon hybridization of a DNA template (see Fig. 2). The production of such oligonucleotide chips adds new procedural avenues to the growing number of applications of DNA microarrays.
• 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.