5'-O-(4,4'-dimethoxytrityl)-3'-deoxythymidinylsulfamido-(3'(N)->5'(N))-5'-deoxythymidine | 193894-21-2

• 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'-O-(4,4'-dimethoxytrityl)-3'-deoxythymidinylsulfamido-(3'(N)->5'(N))-5'-deoxythymidine
• 英文别名: 1-[(2R,4S,5S)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methylsulfamoylamino]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 193894-21-2
• 化学式: C₄₁H₄₆N₆O₁₂S
• 分子量: 846.915
• InChiKey: NFHAKLAKFLMURK-UWNKZCSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  60
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  232
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-3'-deoxythymidinylsulfamido-(3'(N)->5'(N))-5'-deoxythymidine 在 二氯乙酸 作用下， 以 二氯甲烷 为溶剂， 以95%的产率得到3'-deoxythymidinylsulfamido-(3'(N)->5'(N))-5'-deoxythymidine
  参考文献：
  名称：

  二核苷酸中磷酸二酯键的磺酰胺取代：合成和构象分析

  摘要：

  已合成了二核苷酸类似物d（TnsnT）和d（TnsnA），其中d（TpT）和d（TpA）的磷酸二酯键被suflamide [-NHSO 2 NH-]取代。使用3 J邻位偶合常数的构象分析表明，这种修饰导致从主要的南部（C2'-endo）核糖核环构象转变为北部（C3'-endo）核糖环构象。温度和浓度变化对核糖构象的影响表明，修饰的二核苷具有更大的分子内碱基堆积倾向，并且在d（TnsnA）情况下具有自缔合性。

  DOI：

  10.1016/s0040-4020(97)10421-5
• 作为产物：
  描述：

  5-叠氮基-5-脱氧胸腺嘧啶脱氧核苷 在 palladium on activated charcoal 四丁基氟化铵 、 氢气 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 生成 5'-O-(4,4'-dimethoxytrityl)-3'-deoxythymidinylsulfamido-(3'(N)->5'(N))-5'-deoxythymidine
  参考文献：
  名称：

  Synthesis of sulfamide linked dinucleotide analogues

  摘要：

  Novel sulfamide [-NHSO2NH-] linked dinucleotide analogues d(TnsnT) and d(TnsnA) have been synthesised from 3'- and 5'-amino nucleosides. Treatment of these amino nucleosides with catechol sulfate results in the formation of 2-hydroxyphenyl sulfamate eaters which couple smoothly in good yields with either 5'- or 3'-amines of similar nucleosides. NMR studies showed that the 3'-sulfamide group results in a preferential C3'-endo (Northern) sugar conformation. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)01179-9

文献信息

• [EN] LINKAGE MODIFIED OLIGOMERIC COMPOUNDS<br/>[FR] COMPOSÉS OLIGOMÈRES MODIFIÉS PAR LIAISON
  申请人：IONIS PHARMACEUTICALS INC

  公开号：WO2019245957A1

  公开（公告）日：2019-12-26

  The present invention provides gapped oligomeric compounds comprising from 1 to about 3 internucleoside linkages having one of formulas I to XVI. In certain embodiments, inclusion of from 1 to about 3 internucleoside linkages of one of formulas I to XVI, improves selectivity for a target RNA relative to an off target RNA. In certain embodiments, the improved selectivity also provides an improved toxicity profile. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount of activity or expression of the target nucleic acid in a cell.

  本发明提供了包含从1到大约3个核苷酸间连接的间隙寡聚合物化合物，其中所述核苷酸间连接具有I至XVI式中的一种。在某些实施例中，包含I至XVI式中的一种核苷酸间连接，可以提高与目标RNA相对于非靶RNA的选择性。在某些实施例中，提高的选择性还提供了改进的毒性概况。某些这样的寡聚合物化合物适用于与互补核酸杂交，包括但不限于细胞中的核酸。在某些实施例中，杂交导致细胞中目标核酸的活性或表达量的调节。
• Sulfamide replacement of the phosphodiester linkage in dinucleotides: Synthesis and conformational analysis
  作者：Jason Micklefield、Kevin J. Fettes

  DOI：10.1016/s0040-4020(97)10421-5

  日期：1998.3

  suflamide [-NHSO2NH-], have been synthesised. Conformational analysis using 3J vicinal coupling constants shows that this modification results in a shift from a predominantly southern (C2′-endo) to northern (C3′-endo) ribose ring conformation. The effect of temperature and concentration changes on ribose conformation, reveals that the modified dinucleosides have a greater propensity to base stack intramolecularly

  已合成了二核苷酸类似物d（TnsnT）和d（TnsnA），其中d（TpT）和d（TpA）的磷酸二酯键被suflamide [-NHSO 2 NH-]取代。使用3 J邻位偶合常数的构象分析表明，这种修饰导致从主要的南部（C2'-endo）核糖核环构象转变为北部（C3'-endo）核糖环构象。温度和浓度变化对核糖构象的影响表明，修饰的二核苷具有更大的分子内碱基堆积倾向，并且在d（TnsnA）情况下具有自缔合性。
• Synthesis of sulfamide linked dinucleotide analogues
  作者：Jason Micklefield、Kevin J. Fettes

  DOI：10.1016/s0040-4039(97)01179-9

  日期：1997.7

  Novel sulfamide [-NHSO2NH-] linked dinucleotide analogues d(TnsnT) and d(TnsnA) have been synthesised from 3'- and 5'-amino nucleosides. Treatment of these amino nucleosides with catechol sulfate results in the formation of 2-hydroxyphenyl sulfamate eaters which couple smoothly in good yields with either 5'- or 3'-amines of similar nucleosides. NMR studies showed that the 3'-sulfamide group results in a preferential C3'-endo (Northern) sugar conformation. (C) 1997 Elsevier Science Ltd.
• Replacement of the phosphodiester linkage in DNA with sulfamide and 3′-N-sulfamate groups
  作者：Kevin J. Fettes、Nigel Howard、David T. Hickman、Steven A. Adah、Mark R. Player、Paul F. Torrence、Jason Micklefield

  DOI：10.1039/b001586p

  日期：——

  Replacing phosphodiester linkages in DNA with neutral 3′-N-sulfamate groups has little effect on the binding affinity for complementary DNA or RNA, whereas incorporation of sulfamide groups into DNA results in considerable destabilisation of isosequential duplexes.

  用中性取代 DNA 中的磷酸二酯键 3-N-氨基磺酸基团对结合影响很小 与互补 DNA 或 RNA 的亲和力，而掺入磺酰胺 DNA 中的基团导致等序列的相当大的不稳定 复式公寓。