N'-[9-[(1R,4R,6R,7S)-4-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-6-yl]-6-oxo-1H-purin-2-yl]-N,N-dimethylformamidine | 206055-72-3

• 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: N'-[9-[(1R,4R,6R,7S)-4-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-6-yl]-6-oxo-1H-purin-2-yl]-N,N-dimethylformamidine
• 英文别名: 5’-ODMT-LNA-G-iBu；DMTr-LNA-G^lb；Guanosine, 5a(2)-O-[bis(4-methoxyphenyl)phenylmethyl]-2a(2)-O,4a(2)-C-methylene-N-(2-methyl-1-oxopropyl)-；N-[9-[(1R,3R,4R,7S)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 206055-72-3
• 化学式: C₃₆H₃₇N₅O₈
• 分子量: 667.718
• InChiKey: JMGQUFRCVHVMAX-UBMDZZGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  49
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (4R,5S)-oxazaphospholidine 、 N'-[9-[(1R,4R,6R,7S)-4-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-6-yl]-6-oxo-1H-purin-2-yl]-N,N-dimethylformamidine 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 以1.95 g的产率得到D-OAP-LNA-GiBu
  参考文献：
  名称：

  [EN] MULTIPLE COUPLING & OXIDATION METHOD
  [FR] PROCÉDÉ DE COUPLAGE ET D'OXYDATION MULTIPLES

  摘要：

  本发明涉及立体定义的磷硫酸酯寡核苷酸领域，以及立体定义的核苷酸单体和使用该单体合成立体定义的寡核苷酸的方法。本文公开了寡核苷酸增强合成方法，在单个延伸周期内重复耦合和氧化步骤。该方法可提高立体定义的磷硫酸酯寡核苷酸的产量和纯度。

  公开号：

  WO2019002237A1
• 作为产物：
  描述：

  1,2-O-(异丙亚基)-4-C-[(苯基甲氧基)甲基]-3-O-(苯基甲基)-beta-L-来苏呋喃糖 在 palladium dihydroxide 吡啶 、 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 氢气 、 sodium methylate 、 sodium hydride 、 溶剂黄146 、 对甲苯磺酰氯 作用下， 以 甲醇 、 乙醇 、 1,2-二氯乙烷 为溶剂， 生成 N'-[9-[(1R,4R,6R,7S)-4-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-6-yl]-6-oxo-1H-purin-2-yl]-N,N-dimethylformamidine
  参考文献：
  名称：

  LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition

  摘要：

  一类新型的核酸类似物，被称为LNA（锁定核酸），被引入了。根据Watson-Crick碱基配对规则，LNA与互补的DNA和RNA形成双链，具有显著增加的热稳定性和通常提高的选择性。

  DOI：

  10.1039/a708608c

文献信息

• [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。
• 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] PHOSPHONOACETATE GAPMER OLIGONUCLEOTIDES<br/>[FR] OLIGONUCLÉOTIDES GAPMER DE PHOSPHONOACÉTATE
  申请人：ROCHE INNOVATION CT COPENHAGEN AS

  公开号：WO2020169695A1

  公开（公告）日：2020-08-27

  The invention relates to a single stranded antisense gapmer oligonucleotide comprising at least one dinucleoside of formula (I), wherein (A1), (A2) and A are as defined in the description and in the claims. The oligonucleotide according to the invention can be used as a medicament.

  该发明涉及一种包含至少一个式(I)的二核苷酸二聚体的单链反义缺口寡核苷酸，其中（A1）、（A2）和A如描述和权利要求中所定义。根据该发明的寡核苷酸可用作药物。
• [EN] ENHANCED COUPLING OF STEREODEFINED OXAZAPHOSPHOLIDINE PHOSPHORAMIDITE MONOMERS TO NUCLEOSIDE OR OLIGONUCLEOTIDE<br/>[FR] COUPLAGE AMÉLIORÉ DE MONOMÈRES DE PHOSPHORAMIDITE D'OXAZAPHOSPHOLIDINE STÉRÉODÉFINIS À UN NUCLÉOSIDE OU UN OLIGONUCLÉOTIDE
  申请人：ROCHE INNOVATION CT COPENHAGEN AS

  公开号：WO2017194498A1

  公开（公告）日：2017-11-16

  The present invention relates to the field of stereodefined phosphorothioate oligonucleotides and to stereodefining nucleoside monomers and methods of synthesis of stereodefined oligonucleotides. Herein are disclosed solvent compositions which provide enhanced solubility and stability of stereodefining nucleoside monomers, and can be used to improve the coupling efficacy of such monomers in oligonucleotide synthesis.

  本发明涉及立体定义的磷硫酸酯寡核苷酸领域，以及立体定义核苷苷酸单体和立体定义寡核苷酸的合成方法。本文介绍了提供增强溶解性和稳定性的溶剂组合物，可用于提高这些单体在寡核苷酸合成中的偶联效率。
• Oligonucleotide analogues
  申请人：Wengel Jesper

  公开号：US20050287566A1

  公开（公告）日：2005-12-29

  The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs (Locked Nucleoside Analogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.

  本发明涉及新型的双环和三环核苷酸和核苷酸类似物，以及包含这些元素的寡核苷酸。这些核苷酸类似物，即锁定核苷酸类似物（LNAs），能够为寡核苷酸提供与互补RNA和DNA寡聚物的亲和力和特异性方面的有价值的改进。这种新型的LNA修饰的寡核苷酸以及LNA本身在广泛的诊断应用和治疗应用中非常有用。其中包括反义应用、PCR应用、链置换寡聚物、作为核酸聚合酶的底物、作为基于核苷酸的药物等。本发明还涉及这些应用。