5-[(2S,3R,4R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxy-tetrahydrofuran-2-yl]-1-methylpyrimidine-2,4-dione | 875302-41-3

• 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: 5-[(2S,3R,4R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxy-tetrahydrofuran-2-yl]-1-methylpyrimidine-2,4-dione
• 英文别名: 5'-O-(4,4'-dimethoxitrityl)-2'-O-(tert-butyldimethylsilyl)-1-N-methylpseudouridine；5-[(2S,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxyoxolan-2-yl]-1-methylpyrimidine-2,4-dione
• CAS: 875302-41-3
• 化学式: C₃₇H₄₆N₂O₈Si
• 分子量: 674.866
• InChiKey: LAUAFECHUGXCAW-NXVJRICRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.29
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  吡啶 、 5-[(2S,3R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3,4-dihydroxy-tetrahydrofuran-2-yl]-1-methyl-pyrimidine-2,4-dione 、 叔丁基二甲基氯硅烷 在 silver nitrate 氩 、 crude residue 、 ethyl acetate n-hexane 作用下， 以 四氢呋喃 为溶剂， 反应 4.33h， 以to give a pure title compound (780 mg, 25%), and 5′-O-(4,4′-dimethoxitrityl)-3′-O-(tert-butyldimethylsilyl)-1-methylpseudouridine (800 mg, 25%) as amorphous solid的产率得到5-[(2S,3R,4R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxy-tetrahydrofuran-2-yl]-1-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  Oligonucleotides comprising a modified or non-natural nucleobase

  摘要：

  本发明的一个方面涉及含有至少一个非天然核碱基的双链寡核苷酸。在某些实施例中，非天然核碱基是二氟基甲苯基、硝基吲哚基、硝基吡咯基或硝基咪唑基。在一个首选实施例中，非天然核碱基是二氟基甲苯基。在某些实施例中，仅含有双链寡核苷酸的两个寡核苷酸链中的一个包含非天然核碱基。在某些实施例中，包含双链寡核苷酸的两个寡核苷酸链分别独立地包含非天然核碱基。在某些实施例中，寡核苷酸链包含至少一个修饰的糖基团。本发明的另一个方面涉及含有至少一个非天然核碱基的单链寡核苷酸。在一个首选实施例中，非天然核碱基是二氟基甲苯基。在某些实施例中，核苷酸中自然存在的核苷糖分子被替换为六糖、多环杂基烷基环或环己烯基团。在某些实施例中，寡核苷酸中至少有一个磷酸酯连接被替换为磷酸硫酯连接。

  公开号：

  US07579451B2

文献信息

• Oligonucleotides comprising a modified or non-natural nucleobase
  申请人：Manoharan Muthiah

  公开号：US20060035254A1

  公开（公告）日：2006-02-16

  One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

  本发明的一个方面涉及含有至少一个非自然碱基的双链寡核苷酸。在某些实施例中，非自然碱基可以是二氟基甲苯基、硝基吲哚基、硝基吡咯基或硝基咪唑基。在一个首选实施例中，非自然碱基是二氟基甲苯基。在某些实施例中，双链寡核苷酸中的两个寡核苷酸链中只有一个含有非自然碱基。在某些实施例中，双链寡核苷酸中的两个寡核苷酸链都独立地含有非自然碱基。在某些实施例中，寡核苷酸链包含至少一个修饰的糖基。本发明的另一个方面涉及含有至少一个非自然碱基的单链寡核苷酸。在一个首选实施例中，非自然碱基是二氟基甲苯基。在某些实施例中，取代了核苷中天然存在的核糖糖基的是己糖糖基、多环杂烷基环或环己烯基团。在某些实施例中，寡核苷酸中的至少一个磷酸酯键被磷酸硫酯键取代。
• OLIGONUCLEOTIDES COMPRISING A MODIFIED OR NON-NATURAL NUCLEOBASE
  申请人：MANOHARAN Muthiah

  公开号：US20090281298A1

  公开（公告）日：2009-11-12

  One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

  本发明的一个方面涉及至少包含一种非天然核碱基的双链寡核苷酸。在某些实施例中，非天然核碱基是二氟基甲苯基、硝基吲哚基、硝基吡咯基或硝基咪唑基。在一个首选实施例中，非天然核碱基是二氟基甲苯基。在某些实施例中，仅有双链寡核苷酸中的两个寡核苷酸链中的一个包含非天然核碱基。在某些实施例中，包含双链寡核苷酸的两个寡核苷酸链独立地包含非天然核碱基。在某些实施例中，寡核苷酸链包括至少一个修饰的糖基团。本发明的另一个方面涉及至少包含一种非天然核碱基的单链寡核苷酸。在一个首选实施例中，非天然核碱基是二氟基甲苯基。在某些实施例中，核苷中天然存在的核苷糖被替换为六碳糖、多环杂基烷基环或环己烯基团。在某些实施例中，寡核苷酸中的至少一个磷酸酯连接被替换为磷酸硫酯连接。
• NON-NATURAL RIBONUCLEOTIDES, AND METHODS OF USE THEREOF
  申请人：Manoharan Muthiah

  公开号：US20110130440A1

  公开（公告）日：2011-06-02

  One aspect of the present invention relates to modified nucleosides and oligonucleotides comprising such modified nucleosides. Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

  本发明的一个方面涉及改性核苷和包含这种改性核苷的寡核苷酸。本发明的另一个方面涉及一种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）开始的细胞足够长的时间，以获得目标基因的mRNA降解。