(1R,3R,4R,7S)-3-(4-N-benzoyl-5-methylcytosin-1-yl)-1-[4,4'-dimethoxytrityloxymethyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane

• 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: (1R,3R,4R,7S)-3-(4-N-benzoyl-5-methylcytosin-1-yl)-1-[4,4'-dimethoxytrityloxymethyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: N-(1-((1R,3R,4R,7S)-1-((Bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-5-methyl-2-oxo-1,2-dihydropyrimidin-4-yl)benzamide；N-[1-[(1R,3R,4R,7S)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-5-methyl-2-oxopyrimidin-4-yl]benzamide
• 化学式: C₃₉H₃₇N₃O₈
• 分子量: 675.738
• InChiKey: CTGWFRQUULNNIN-OSZGUBSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  50
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 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：

  (1R,3R,4R,7S)-3-(4-N-benzoyl-5-methylcytosin-1-yl)-1-[4,4'-dimethoxytrityloxymethyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane 在 三氯乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以65%的产率得到(1S,3R,4R,7S)-7-hydroxy-1-hydroxymethyl-3-(5-methyl-4-N-benzoylcytosine-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Chemical Synthesis of LNA-mCTP and Its Application for MicroRNA Detection

  摘要：

  Locked nucleic acids (LNA) are being applied in hybridization studies, but current locked nucleotides cannot be transcribed into RNA probes. Here, the authors report the use of a new synthetic locked nucleotide, locMeCytidine-5'-triphosphate (LNA-mCTP), for hybridization study. This synthetic LNA-mCTP can be transcribed into a short (similar to 30-nt) RNA probe. Dot blot hybridization on nylon membrane suggested that the short P-33-LNA RNA probes had strong binding affinity to target oligonucleotides and its detection sensitivity was approximately similar to 1000 miRNAs in a 20- to 30-m (diameter) dot area. On tissue sections, the differential expression pattern of mir-124 within different tissue regions revealed by short P-33- LNA RNA probes correlated well to that analyzed by real-time RT-PCR. In addition, the specific cellular distribution of vasoactive intestinal polypeptide mRNAs in the mouse brain was the same using a 30-nt P-33-LNA RNA probe and a 1.5-kb P-33-RNA probe. These results suggested the high hybridization specificity of the small LNA-RNA probes to target small RNAs. Finally, the authors applied P-33-LNA probes to detect miRNA let-7C expression in human cancer tissues. Let-7C was clearly present in lung, prostate, and colon cancers but undetectable in ovary and thyroid cancer samples. These results suggested that this miRNA detection method provides an alternative tool to study the cellular distribution of miRNAs in tissues.

  DOI：

  10.1080/15257770701571693
• 作为产物：
  描述：

  1-[(1R,4R,6R,7S)-4-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-6-yl]-5-methylpyrimidine-2,4-dione 在 吡啶 、 ammonium hydroxide 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 (1R,3R,4R,7S)-3-(4-N-benzoyl-5-methylcytosin-1-yl)-1-[4,4'-dimethoxytrityloxymethyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Conformationally restricted triplex-forming oligonucleotides (TFOs). Binding properties of α-l-LNA and introduction of the N7-glycosylated LNA-guanosine

  摘要：

  The method for scaled-up production of alpha-L-LNA phosphoramidite building blocks containing thymine and 5-methylcytosine nucleobases is described. Binding properties of pyrimidine TFOs modified with alpha-L-LNA are reported. In contrast to LNA TFOs, the fully modified a-L-LNA forms a stable triplex with a model DNA duplex. Pyrimidine DNA/LNA/alpha-L-LNA chimeras also efficiently hybridize with a model DNA duplex in the parallel mode. LNA nucleoside containing unnatural N-7-glycosylated guanine (LNA-(7) G) was synthesized by a convergent method and incorporated into LNA oligonucleotides. The triplex-forming alternating DNA/LNA oligonucleotides containing a single LNA-(7) G modification instead of internal LNA-mC demonstrate improved pH-dependent properties. The single LNA-(7) G modification can also discriminatively reduce competitive binding of TFOs to natural nucleic acids in the antiparallel duplex mode. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.04.016

文献信息

• [EN] S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS<br/>[FR] POLYMÈRES OLIGONUCLÉOTIDIQUES INHIBANT LE TRANSPORT DE L'ANTIGÈNE S ET MÉTHODES
  申请人：ALIGOS THERAPEUTICS INC

  公开号：WO2021119325A1

  公开（公告）日：2021-06-17

  Various embodiments provide STOPS™ polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS™ modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS™ modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.

  各种实施方式提供了STOPS™聚合物，这些聚合物是S-抗原转运抑制寡核苷酸聚合物，提供了制备它们的方法以及使用它们治疗疾病和症状的方法。在某些实施方式中，STOPS™修饰的寡核苷酸包括至少部分磷硫酸酯化的交替A和C单元序列，具有如本文所述的修饰。通过HBsAg分泌测定确定的STOPS™修饰的寡核苷酸对乙型肝炎的序列无关抗病毒活性，其EC50小于100 nM。
• [EN] NOVEL PHOSPHORAMIDITES<br/>[FR] NOUVELLES PHOSPHORAMIDITES
  申请人：ROCHE INNOVATION CT COPENHAGEN AS

  公开号：WO2020169696A1

  公开（公告）日：2020-08-27

  The invention relates to a compound of formula (II) wherein X, Y, R5, Rx, Ry and Nu are as defined in the description and in the claims. The compound of formula (II) can be used in the manufacture of medicaments.

  该发明涉及具有公式（II）的化合物，其中X、Y、R5、Rx、Ry和Nu如描述和索赔中所定义。公式（II）的化合物可用于制造药物。
• [EN] NOVEL PROCESS FOR PREPARING NUCLEOTIDE P(V) MONOMERS<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE MONOMÈRES P(V) NUCLÉOTIDIQUES
  申请人：ROCHE INNOVATION CT COPENHAGEN AS

  公开号：WO2020212301A1

  公开（公告）日：2020-10-22

  The present invention relates to an optimized method for preparing a P(V) monomer of formula (IIIa) or (IIIb) from a nucleoside using DBU as a base at about 0.8 equivalent to nucleoside.

  本发明涉及一种优化的方法，用DBU作为碱在约0.8当量的情况下，从核苷酸制备公式(IIIa)或(IIIb)的P(V)单体。
• Preparation of LNA Phosphoramidites
  作者：Daniel Sejer Pedersen、Christoph Rosenbohm、Troels Koch

  DOI：10.1055/s-2002-25756

  日期：——

  A highly efficient method for the preparation of LNA (Locked Nucleic Acid) phosphoramidite monomers with 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite and 4,5-dicyanoimidazole has been devised. The quality of the phosphoramidites prepared in this manner is equal to HPLC purified phosphoramidites and can easily be used for oligonucleotide synthesis without further purification. In addition the possibility of using 4,5-dicyanoimidazole in catalytic amounts has been investigated and showed optimum results when 0.7 equivalent was used, and that reducing the amount further leads to undesired phosphitylation of the nucleobase.Furthermore it is demonstrated that LNA phosphoramidite monomers are exceedingly stable in acetonitrile solution thereby prolonging the effective lifetime of the reagent significantly.

  已设计出一种高效制备LNA（锁核酸）磷酰胺单体的方法，该方法使用2-氰乙基-N,N,N',N'-四异丙基磷酸二酰胺和4,5-二氰基咪唑。以此方式制备的磷酰胺质量与HPLC纯化的磷酰胺相当，无需进一步纯化即可轻松用于寡核苷酸合成。此外，研究了使用催化量的4,5-二氰基咪唑的可能性，并发现当使用0.7当量时获得最佳结果，而进一步减少用量会导致核苷碱基的不希望的磷酸化。此外，实验证明LNA磷酰胺单体在乙腈溶液中极为稳定，从而显著延长了试剂的有效使用寿命。
• [EN] NOVEL PROCESS FOR MAKING ALLOFURANOSE FROM GLUCOFURANOSE<br/>[FR] NOUVEAU PROCÉDÉ DE FABRICATION D'ALLOFURANOSE À PARTIR DE GLUCOFURANOSE
  申请人：ROCHE INNOVATION CT COPENHAGEN AS

  公开号：WO2019224172A1

  公开（公告）日：2019-11-28

  The present invention relates to the manufacture of allofuranose from glucofuranose as defined in the description and in the claim. Allofuranos is an intermediate in the manufacture of oligonucleotides which can be used as a medicament.

  本发明涉及从描述和权利要求中定义的葡糖呋喃糖中制备阿洛呋喃糖。阿洛呋喃糖是合成寡核苷酸时的中间体，可用作药物。