N-(1-((2r,3r,4r,5r)-5-((双(4-甲氧基苯基)(苯基)甲氧基)甲基)-4-羟基-3-甲氧基四氢呋喃-2-基)-2-氧代-1,2-二氢嘧啶-4-基)乙酰胺 | 199593-08-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: N-(1-((2r,3r,4r,5r)-5-((双(4-甲氧基苯基)(苯基)甲氧基)甲基)-4-羟基-3-甲氧基四氢呋喃-2-基)-2-氧代-1,2-二氢嘧啶-4-基)乙酰胺
• 中文别名: N4-乙酰基-5'-O-(4,4'-二甲氧基三苯甲基)-2'-甲氧基胞苷；N-乙酰基-5'-O-(4,4'-二甲氧基三苯甲基)-2'-甲氧基胞苷
• 英文名称: N-(1-((2R,3R,4R,5R)-5-((bis(4-Methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxy-3-methoxytetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide
• 英文别名: 10-acetyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-methylcytidine；N-acetyl-5'-O-[bis(4-methoxyphenyl)phenylmethyl]-2'-O-methylcytidine；N⁴-acetyl-5'-O-DMTr-2'-O-methylcytidine；N-[1-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxy-3-methoxyoxolan-2-yl]-2-oxopyrimidin-4-yl]acetamide
• CAS: 199593-08-3
• 化学式: C₃₃H₃₅N₃O₈
• 分子量: 601.656
• InChiKey: FINUHOJILDNELQ-PMFUCWTESA-N

物化性质

• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H320,H335
• 储存条件：
  2-8℃，保持干燥

反应信息

• 作为反应物：
  描述：

  N-(1-((2r,3r,4r,5r)-5-((双(4-甲氧基苯基)(苯基)甲氧基)甲基)-4-羟基-3-甲氧基四氢呋喃-2-基)-2-氧代-1,2-二氢嘧啶-4-基)乙酰胺 在 吡啶 、 氯化亚砜 、 N,N'-二环己基碳二亚胺 、 2,2-二甲氧基丙烷 作用下， 以 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

  5'-END DERIVATIVES

  摘要：

  本发明提供了式（1）的化合物。发明的另一个方面涉及抑制细胞中基因表达的方法，该方法包括（a）将本发明的寡核苷酸与细胞接触；以及（b）维持从步骤（a）中的细胞足够时间以获得目标基因mRNA的降解。

  公开号：

  US20130323836A1
• 作为产物：
  描述：

  N-乙酰胞嘧啶核苷 在 吡啶 、 四丁基氟化铵 、 silver(l) oxide 作用下， 以 四氢呋喃 、 苯 为溶剂， 生成 N-(1-((2r,3r,4r,5r)-5-((双(4-甲氧基苯基)(苯基)甲氧基)甲基)-4-羟基-3-甲氧基四氢呋喃-2-基)-2-氧代-1,2-二氢嘧啶-4-基)乙酰胺
  参考文献：
  名称：

  Ultrafast Cleavage and Deprotection of Oligonucleotides Synthesis and Use of C^AcDerivatives

  摘要：

  We have investigated the use of alkylamines as fast cleavage and deprotection reagents for the solid phase synthesis of oligonucleotides and found methylamine/ammonium hydroxide (or methylamine) as an efficient reagent. The transamination side product formed with the commonly used dC(bz) has been eliminated by the use of dC(Ac) phosphoramidite. This system has successfully been used in the synthesis of oligonucleotides and oligonucleoside phosphorothioates. DMT dC(Ac) hydrogen phosphonate and DMT ribo C-Ac-2'-OMe phosphoramidite also have been prepared and used in the synthesis of oligonucleotides.

  DOI：

  10.1080/07328319708006236

文献信息

• PHOSPHORAMIDITE BUILDING BLOCKS FOR SUGAR-CONJUGATED OLIGONUCLEOTIDES
  申请人：AM CHEMICALS LLC

  公开号：US20160083414A1

  公开（公告）日：2016-03-24

  Novel nucleoside phosphoramidite building blocks for preparation of synthetic oligonucleotides containing at least one phosphotriester linkage conjugated to a monosaccharide and synthetic processes for making the same are disclosed. Furthermore, oligomeric compounds are prepared using said building blocks, preferably followed by removal of protecting groups to provide monosaccharide-conjugated oligonucleotides.

  揭示了用于制备含至少一种磷酸三酯键连接的寡核苷酸的合成寡核苷酸的新型核苷酸磷酰胺酯构建模块，其与单糖偶联，并公开了制备这些构建模块的合成过程。此外，使用这些构建模块制备寡聚合物化合物，最好是在去除保护基之后，以提供单糖偶联的寡核苷酸。
• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR SYNTHESIS<br/>[FR] COMPOSÉS, COMPOSITIONS ET PROCÉDÉS DE SYNTHÈSE
  申请人：WAVE LIFE SCIENCES LTD

  公开号：WO2018237194A1

  公开（公告）日：2018-12-27

  The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

  本公开内容提供了合成技术，包括用于立体选择性合成的试剂和方法。在某些实施例中，本公开内容提供了作为手性辅助剂有用的化合物。在某些实施例中，本公开内容提供了用于寡核苷酸合成的试剂和方法。在某些实施例中，本公开内容提供了用于手性控制寡核苷酸制备的试剂和方法。在某些实施例中，本公开内容的技术特别适用于构建具有挑战性的核苷酸间连接，提供高产率和立体选择性。
• [EN] OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF<br/>[FR] COMPOSITIONS D'OLIGONUCLÉOTIDES ET PROCÉDÉS ASSOCIÉS
  申请人：WAVE LIFE SCIENCES LTD

  公开号：WO2021237223A1

  公开（公告）日：2021-11-25

  The present disclosure provides modified oligonucleotides and compositions and methods thereof. In some embodiments, provided technologies comprise modified sugars and/or modified internucleotidic linkages. In some embodiments, the present disclosure provides technologies for preparing modified oligonucleotides. In some embodiments, the present disclosure provides chirally controlled oligonucleotide compositions and methods for their preparation and uses.

  本公开提供了经修改的寡核苷酸及其组合物和方法。在某些实施方式中，提供的技术包括修改的糖或修改的核苷酸间连接。在某些实施方式中，本公开提供了用于制备修改的寡核苷酸的技术。在某些实施方式中，本公开提供了对手性控制的寡核苷酸组合物及其制备和用途的方法。
• Synthesis and biological activity of phosphonoacetate- and thiophosphonoacetate-modified 2′-O-methyl oligoribonucleotides
  作者：Richard N. Threlfall、Adrian G. Torres、Angelika Krivenko、Michael J. Gait、Marvin H. Caruthers

  DOI：10.1039/c1ob06614e

  日期：——

  Chimeric 2′-O-methyl oligoribonucleotides (2′-OMe ORNs) containing internucleotide linkages which were modified with phosphonoacetate (PACE) or thiophosphonoacetate (thioPACE) were prepared by solid-phase synthesis. The modified 2′-OMe ORNs contained a central phosphate or phosphorothioate sequence with up to 4 PACE or thioPACE modifications, respectively, at either end of the ORN in a “gapmer” motif. Both PACE and thioPACE 2′-OMe ORNs formed stable duplexes with complementary RNA. The majority of these duplexes had higher thermal melting temperatures than an unmodified RNA:RNA duplex. The modified 2′-OMe ORNs were effective passenger strands with complementary, unmodified siRNAs, for inducing siRNA activity in a dual luciferase assay in the presence of a lipid transfecting agent. As single strands, thioPACE 2′-OMe ORNs were efficiently taken up by HeLa cells in the absence of a lipid transfecting agent. Furthermore, thioPACE modifications greatly improved the potency of a 2′-OMe phosphorothioate ORN as an inhibitor of microRNA-122 in Huh7 cells, without lipid transfection.

  通过固相合成法制备了含有核苷酸内连接的嵌合 2â²-O-甲基寡核苷酸（2â²-OMe ORNs），这些嵌合寡核苷酸经磷酸乙酸酯（PACE）或硫代磷酸乙酸酯（thioPACE）修饰。经修饰的2â²-OMe ORN包含一个中心磷酸或硫代磷酸序列，在ORN的两端分别有多达4个PACE或thioPACE修饰，形成一个 "间隙 "图案。PACE 和 thioPACE 2â²-OMe ORN 都能与互补 RNA 形成稳定的双链体。与未修饰的 RNA:RNA 双链相比，这些双链中的大多数具有更高的热熔温度。修饰的 2-OMe ORN 与互补的、未修饰的 siRNA 是有效的客链，可在有脂质转染剂存在的双荧光素酶试验中诱导 siRNA 活性。作为单链，thioPACE 2â²-OMe ORNs 能在没有脂质转染剂的情况下被 HeLa 细胞有效吸收。此外，硫代PACE修饰大大提高了2â²-OMe硫代磷酸酯ORN在Huh7细胞中作为microRNA-122抑制剂的效力，而无需脂质转染。
• Photo-tethered molecular beacons for superior light-induction
  作者：Robin Klimek、Mantian Wang、Vivien R. McKenney、Erin M. Schuman、Alexander Heckel

  DOI：10.1039/d0cc06704k

  日期：——

  We developed a superior class of light-activatable molecular beacons with photo-tethered loop regions. Two simple modifications and probe cyclisation prevent the molecular beacon from hybridising with the target RNA before light-activation. Full activity of the molecular beacon is elicited upon illumination with 365 nm light.

  我们开发了具有光链接环区域的上一类光激活分子信标。两个简单的修改和探针环化作用可防止分子信标在光激活之前与目标RNA杂交。在用365 nm光照射时，会激发出分子信标的全部活性。