5-O-(tert-butyldiphenylsilyl)-4-C-((S)-1-hydroxyethyl)-1,2-O-isopropylidene-3-O-(2-naphthylmethyl)-α-D-ribofuranose

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-O-(tert-butyldiphenylsilyl)-4-C-((S)-1-hydroxyethyl)-1,2-O-isopropylidene-3-O-(2-naphthylmethyl)-α-D-ribofuranose
• 英文别名: |A-L-Mannofuranose, 6-deoxy-4-C-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]methyl]-1,2-O-(1-methylethylidene)-3-O-(2-naphthalenylmethyl)-；(1S)-1-[(3aR,5S,6S,6aR)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,2-dimethyl-6-(naphthalen-2-ylmethoxy)-6,6a-dihydro-3aH-furo[2,3-d][1,3]dioxol-5-yl]ethanol
• 化学式: C₃₇H₄₄O₆Si
• 分子量: 612.838
• InChiKey: LMUNKMCTPNQJAF-ACODDNCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.93
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  66.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-O-(tert-butyldiphenylsilyl)-4-C-((S)-1-hydroxyethyl)-1,2-O-isopropylidene-3-O-(2-naphthylmethyl)-α-D-ribofuranose 在 硫酸 吡啶 、 甲醇 、 锂硼氢 、 sodium azide 、 N,O-双三甲硅基乙酰胺 、 草酰氯 、 sodium cyanoborohydride 、 potassium carbonate 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 124.25h， 生成 1-((1R,3R,4R,6S,7S)-7-hydroxy-1-(hydroxymethyl)-5,6-dimethyl-2-oxa-5-azabicyclo[2.2.1]heptan-3-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  [EN] SUBSTITUTED 2 '-AMINO AND 2 '-THIO-BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM
  [FR] 2'-AMINO- ET 2'-THIO-NUCLÉOSIDES BICYCLIQUES SUBSTITUÉS ET COMPOSÉS OLIGOMÈRES PRÉPARÉS À PARTIR DE CES DERNIERS

  摘要：

  本文提供了由2'-氨基和2'-硫代双环核苷和寡聚物化合物制备而成。本文提供的新型双环核苷预计可用于增强其所包含的寡聚物化合物的一个或多个性质，如核酸酶抗性。

  公开号：

  WO2011156202A1
• 作为产物：
  描述：

  1,2:5,6-二异亚丙基-alpha-D-异呋喃糖 在 sodium periodate 、 cerium(III) chloride 、 草酰氯 、 sodium hydride 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 87.91h， 生成 5-O-(tert-butyldiphenylsilyl)-4-C-((S)-1-hydroxyethyl)-1,2-O-isopropylidene-3-O-(2-naphthylmethyl)-α-D-ribofuranose
  参考文献：
  名称：

  6-Disubstituted Or Unsaturated Bicyclic Nucleic Acid Analogs

  摘要：

  本公开描述了6-二取代双环核苷酸、从中制备的寡聚化合物以及使用这些寡聚化合物的方法。更具体地说，这些6-二取代双环核苷酸每个包括一个2′-O—C(Ri)(R2)-4′或2′-O—C=(R3)(R4)-4′桥，其中每个R独立地是一个取代基，而Ri和R2包括H。这些6-二取代双环核苷酸对增强包括核酸酶抗性在内的寡聚化合物的性质是有用的。在某些实施例中，本文提供的寡聚化合物与靶RNA的部分杂交，导致靶RNA的正常功能丧失。

  公开号：

  US20110053881A1

文献信息

• BICYCLIC MORPHOLINO COMPOUNDS AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM
  申请人：Ionis Pharmaceuticals, Inc.

  公开号：US20160186175A1

  公开（公告）日：2016-06-30

  The present invention provides bicyclic morpholino compounds and oligomeric compounds prepared therefrom. More particularly, incorporation of one or more of the bicyclic morpholino compounds into an oligomeric compound is expected to enhance one or more properties of the oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

  本发明提供双环吗啉化合物及其制备的寡聚化合物。更具体地，将一个或多个双环吗啉化合物并入寡聚化合物中，预计会增强寡聚化合物的一种或多种性质。此类寡聚化合物也可以包含在双链结构中。在某些实施例中，本发明提供的寡聚化合物预计会与目标RNA的一部分杂交，导致目标RNA的正常功能丧失。
• [EN] 5'-SUBSTITUTED BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM<br/>[FR] NUCLÉOSIDES BICYCLIQUES 5'-SUBSTITUÉS ET COMPOSÉS OLIGOMÈRES SYNTHÉTISÉS À PARTIR DESDITS NUCLÉOSIDES
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2011115818A1

  公开（公告）日：2011-09-22

  Provided herein are novel 5'-(S)-CH3 substituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the furanose ring of each of the novel 5'-(S)-CH3 substituted bicyclic nucleosides includes a 2' to 4' bridging group. The 5'-(S)-CH3 substituted bicyclic nucleosides are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as for example increasing the binding affinity. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

  本文提供了新颖的5'-(S)-CH3取代的双环核苷，以及由其制备的寡聚化合物和使用这些寡聚化合物的方法。更具体地，每个新颖的5'-(S)-CH3取代的双环核苷的呋喃糖环包括一个2'到4'的桥联基团。预计这些5'-(S)-CH3取代的双环核苷将有助于增强它们所并入的寡聚化合物的一个或多个性质，例如增加结合亲和力。在某些实施例中，本文提供的寡聚化合物与靶RNA的部分杂交，导致靶RNA的正常功能丧失。
• Substituted 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
  申请人：Isis Pharmaceuticals, Inc.

  公开号：US09029335B2

  公开（公告）日：2015-05-12

  Provided herein are novel bicyclic nucleosides, oligomeric compounds that include such bicyclic nucleosides and methods of using the oligomeric compounds. More particularly, the novel bicyclic nucleosides comprise a furanose ring system having a bridge comprising a 4′-methylene group attached to a 2′-sulfoxide or sulfone group and optionally including one or more substituent groups attached to the 4′-methylene and or the 5′-position. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

  本文提供了一种新颖的双环核苷，包括包含这种双环核苷的寡聚化合物以及使用这些寡聚化合物的方法。更具体地说，这种新颖的双环核苷包括一个呋喃糖环系统，其中包括一个桥，该桥包括连接到2'-亚砜或砜基团的4'-亚甲基基团，并且可选地包括连接到4'-亚甲基和/或5'-位置的一个或多个取代基团。在某些实施方式中，本文提供的寡聚化合物预计会与靶RNA的部分杂交，导致靶RNA的正常功能丧失。
• 6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
  申请人：Swayze E. Eric

  公开号：US20070249049A1

  公开（公告）日：2007-10-25

  The present invention provides 6-modified bicyclic nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 6-position. These bicyclicnucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance.

  本发明提供了6-修饰的双环核苷类似物和包含这些核苷类似物的寡聚化合物。在优选实施例中，核苷类似物在6位点具有(R)或(S)-手性。这些双环核苷类似物对提高包括核酸酶抗性在内的寡聚化合物的性能是有用的。
• Synthesis and Biophysical Evaluation of 2′,4′-Constrained 2′<i>O</i>-Methoxyethyl and 2′,4′-Constrained 2′<i>O</i>-Ethyl Nucleic Acid Analogues
  作者：Punit P. Seth、Guillermo Vasquez、Charles A. Allerson、Andres Berdeja、Hans Gaus、Garth A. Kinberger、Thazha P. Prakash、Michael T. Migawa、Balkrishen Bhat、Eric E. Swayze

  DOI：10.1021/jo902560f

  日期：2010.3.5

  We have recently shown that combining the structural elements of 2'O-methoxyethyl (MOE) and locked nuclecic acid (LNA) nucleosides yielded a series of nucleoside modification (cMOE, 2',4'-constrained MOE; cEt, 2',4'-constrained ethyl) that display improved potency over MOE and an improved therapeutic index relative to that of LNA antisense oligonucleotides. In this report we present details regarding the synthesis of the cMOE and cEt nucleoside phosphoramidites and the biophysical evaluation of oligonucleotides containing these nucleoside modification. The synthesis of the cMOE and eEt nucleoside phosphoramidites was efficiently accomplished starting from inexpensive commercially available diacetone allofuranose. The synthesis features the use of a seldom used 2-naphthylmethyl protecting group that provides crystalline intermediates during the synthesis and can be cleanly deprotected under mild conditions. The synthesis was greatly facilitated by the crystallinity of a key mono-TBDPS-protected diol intermediate. In the case of the cEt nucleosides, the introduction of the methyl group in either configuration was accomplished in a stereoselective manner. Ring closure of the 2'-hydroxyl group onto a secondary mesylate leaving group with clean inversion of stereochemistry was achieved under suprisingly mild conditions. For the S-cEt modification, the synthesis of all four (thymine, 5-methylcytosine, adenine, and guanine) nucleobase-modified phosphoramidites was accomplished on a multigram scale. Biophysical evaluation of the cMOE- and cEt-containing oligonucletides revealed that they possess hybridization and mismatch discrimination attributes similar to those of LNA but greatly improved resistance to exonuclease digestion.