1-[(2R,4S,5R)-5-{2-[Bis-(4-methoxy-phenyl)-phenyl-methoxy]-ethyl}-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-yl]-5-methyl-1H-pyrimidine-2,4-dione | 189194-83-0

• 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: 1-[(2R,4S,5R)-5-{2-[Bis-(4-methoxy-phenyl)-phenyl-methoxy]-ethyl}-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-yl]-5-methyl-1H-pyrimidine-2,4-dione
• 英文别名: 1-[(2R,4S,5R)-5-[2-[bis(4-methoxyphenyl)-phenylmethoxy]ethyl]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 189194-83-0
• 化学式: C₃₈H₄₈N₂O₇Si
• 分子量: 672.894
• InChiKey: CVOWXIGGXXRVGT-OUYGKKDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.94
• 重原子数：
  48.0
• 可旋转键数：
  12.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  101.01
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  1-[(2R,4S,5R)-5-{2-[Bis-(4-methoxy-phenyl)-phenyl-methoxy]-ethyl}-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-yl]-5-methyl-1H-pyrimidine-2,4-dione 在 四丁基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 Diisopropyl-phosphoramidous acid (2R,3R,5R)-2-{2-[bis-(4-methoxy-phenyl)-phenyl-methoxy]-ethyl}-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-ylmethyl ester 2-cyano-ethyl ester
  参考文献：
  名称：

  Oligodeoxynucleotides with Extended 3'- and 5'-Homologous Internucleotide Linkages.

  摘要：

  3'-Deoxy-3'-C-(hydroxymethyl)thymidine (3'-DHMT) and 5'-deoxy-5'-C-(hydroxymethyl)thymidine (5'-DHMT) have been prepared and used for the synthesis of novel oligodeoxynucleotides containing extended internucleotide linkages. Enzymatic stability toward exonuclease III degradation was studied and hybridization properties were tested, The extended 3'-homologous DNA causes complete cessation of exonuclease III degradation while the extended 5'-homologous DNA shows only same decrease in degradation. Duplexes having extended internucleotide linkages show a minor decrease in hybridization stability. Tripler formation with 20-mer duplexes at pH 5.5 and high salt concentration gave almost no decrease in binding affinity when compared with unmodified tripler formation. UV experiments were also performed with oligodeoxynucleotides containing hairpin structures and bulged bases, Extended linkages in the oligodeoxynucleotides gave a small increase in T-m with sequences containing a loop, but no change or only a small decrease was observed when an extra thymidine nucleotide was incorporated in the complementary strand.

  DOI：

  10.3891/acta.chem.scand.51-0318
• 作为产物：
  描述：

  5′-deoxy-5′-C-methenyl-3′-O-(tert-butyldimethylsilyl)thymidine 在 吡啶 、 sodium hydroxide 、 1,2-thioxane 、 BH₃*oxathiane 、 硼烷 作用下， 反应 3.25h， 生成 1-[(2R,4S,5R)-5-{2-[Bis-(4-methoxy-phenyl)-phenyl-methoxy]-ethyl}-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-yl]-5-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Oligodeoxynucleotides with Extended 3'- and 5'-Homologous Internucleotide Linkages.

  摘要：

  3'-Deoxy-3'-C-(hydroxymethyl)thymidine (3'-DHMT) and 5'-deoxy-5'-C-(hydroxymethyl)thymidine (5'-DHMT) have been prepared and used for the synthesis of novel oligodeoxynucleotides containing extended internucleotide linkages. Enzymatic stability toward exonuclease III degradation was studied and hybridization properties were tested, The extended 3'-homologous DNA causes complete cessation of exonuclease III degradation while the extended 5'-homologous DNA shows only same decrease in degradation. Duplexes having extended internucleotide linkages show a minor decrease in hybridization stability. Tripler formation with 20-mer duplexes at pH 5.5 and high salt concentration gave almost no decrease in binding affinity when compared with unmodified tripler formation. UV experiments were also performed with oligodeoxynucleotides containing hairpin structures and bulged bases, Extended linkages in the oligodeoxynucleotides gave a small increase in T-m with sequences containing a loop, but no change or only a small decrease was observed when an extra thymidine nucleotide was incorporated in the complementary strand.

  DOI：

  10.3891/acta.chem.scand.51-0318

文献信息

• Insertion of a methylene group into the backbone of an antisense oligonucleotide reveals the importance of deoxyribose recognition by RNase H
  作者：Yoshiaki Masaki、Ayano Tabira、Shihori Hattori、Shunsuke Wakatsuki、Kohji Seio

  DOI：10.1039/d2ob01667b

  日期：——

  the question of whether the interaction of phosphate groups or deoxyriboses is more important in the recognition of DNA/RNA duplex by RNase H. To answer this question, we investigated the effect of methylene group insertion at the 5′-upstream or 3′-downstream phosphorothioate groups on RNase H-mediated cleavage. By inserting a methylene group at the 5′-upside or 3′-downside, the distance between phosphates

  RNase H 作为反义寡核苷酸 (ASO) 基因敲低的关键效应子。尽管已经开发出各种化学修饰来调节 RNase H 介导的裂解，但尚未实现精确控制。在这项研究中，我们试图解决磷酸基团或脱氧核糖的相互作用在 RNase H 识别 DNA/RNA 双链体中是否更重要的问题。为了回答这个问题，我们研究了亚甲基插入在 5 RNase H 介导的裂解上的 '-上游或 3'-下游硫代磷酸酯基团。通过在 5'-上侧或 3'-下侧插入亚甲基，磷酸盐或脱氧核糖之间的距离可以以不同的方式改变。通过堆叠 RNase H 中的 W221 残基。这种效应在不同的序列以及错配的双链体中观察到，表明脱氧核糖环与 RNase H 的相互作用比磷酸基团的相互作用更重要。我们的结果将有助于设计进一步的分子修饰，提高 RNase H 介导的裂解反应的选择性，从而开发等位基因特异性 ASO。