(2R,3S,5R)-2-(((3-(benzhydryloxy)-1,1,1,5,5,5-hexamethyltrisiloxan-3-yl)oxy)methyl)-5-(6-oxo-2-((tris(4-methoxyphenyl)methyl)amino)-1,6-dihydro-9H-purin-9-yl)tetrahydrofuran-3-yl methyl diisopropylphosphoramidite | 950202-99-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3S,5R)-2-(((3-(benzhydryloxy)-1,1,1,5,5,5-hexamethyltrisiloxan-3-yl)oxy)methyl)-5-(6-oxo-2-((tris(4-methoxyphenyl)methyl)amino)-1,6-dihydro-9H-purin-9-yl)tetrahydrofuran-3-yl methyl diisopropylphosphoramidite
• CAS: 950202-99-0
• 化学式: C₅₈H₇₇N₆O₁₁PSi₃
• 分子量: 1149.51
• InChiKey: QOVMUWGOOANSEY-IOBBNVBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.18
• 重原子数：
  79.0
• 可旋转键数：
  26.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  171.14
• 氢给体数：
  2.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  、 、 (2R,3S,5R)-2-(((3-(benzhydryloxy)-1,1,1,5,5,5-hexamethyltrisiloxan-3-yl)oxy)methyl)-5-(2-oxo-4-((tris(4-methoxyphenyl)methyl)amino)pyrimidin-1(2H)-yl)tetrahydrofuran-3-yl methyl diisopropylphosphoramidite 、 (2R,3S,5R)-2-(((3-(benzhydryloxy)-1,1,1,5,5,5-hexamethyltrisiloxan-3-yl)oxy)methyl)-5-(6-((bis(4-methoxyphenyl)(phenyl)methyl)amino)-9H-purin-9-yl)tetrahydrofuran-3-yl methyl diisopropylphosphoramidite 、 (2R,3S,5R)-2-(((3-(benzhydryloxy)-1,1,1,5,5,5-hexamethyltrisiloxan-3-yl)oxy)methyl)-5-(6-oxo-2-((tris(4-methoxyphenyl)methyl)amino)-1,6-dihydro-9H-purin-9-yl)tetrahydrofuran-3-yl methyl diisopropylphosphoramidite 在 四氮唑 、 borane tetrahydrofuran 作用下， 以 乙腈 、 四氢呋喃 为溶剂， 反应 0.03h， 生成 d(T_bC_bT_bT_bA_bC_bT_bG_bA_bT) boranephosphonate oligo-2'-deoxyribonucleotide
  参考文献：
  名称：

  新型寡核苷酸类似物的合成及生化活性

  摘要：

  硼烷膦酸酯脱氧寡核苷酸由 5'-O-benzhydroxybis(trimethylsilyloxy)silyl-2'-deoxynucleoside-3'-phosphoramidites 合成。腺嘌呤和胞嘧啶的环外胺分别用二甲氧基三苯甲基和三甲氧基三苯甲基保护，而鸟嘌呤用 N2-（9-芴基甲氧基羰基）或 N2-三甲氧基三苯甲基保护。胸腺嘧啶用 N3-苯甲酰基保护。使用这些合成子并在标准条件下通过四唑活化，观察到超过 99% 的缩合。用 THF·BH3 或过氧阴离子溶液氧化，然后用氟化物裂解甲硅烷基醚完成一个循环。在合成合适的低聚物后，依次使用乙酸、二硫醇盐和氢氧化铵去除保护基团。

  DOI：

  10.1080/10426500701734745
• 作为产物：
  描述：

  二苯甲基氧基双(三甲基甲硅烷基氧基)氯硅烷 在 咪唑 、 5-甲硫基四氮唑 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (2R,3S,5R)-2-(((3-(benzhydryloxy)-1,1,1,5,5,5-hexamethyltrisiloxan-3-yl)oxy)methyl)-5-(6-oxo-2-((tris(4-methoxyphenyl)methyl)amino)-1,6-dihydro-9H-purin-9-yl)tetrahydrofuran-3-yl methyl diisopropylphosphoramidite
  参考文献：
  名称：

  Solid-Phase Synthesis, Thermal Denaturation Studies, Nuclease Resistance, and Cellular Uptake of (Oligodeoxyribonucleoside)methylborane Phosphine–DNA Chimeras

  摘要：

  The major hurdle associated with utilizing oligo-deoxyribonucleotides for therapeutic purposes is their poor delivery into cells coupled with high nuclease susceptibility. In an attempt to combine the nonionic nature and high nuclease stability of the P-C bond of methylphosphonates with the high membrane permeability, low toxicity, and improved gene silencing ability of borane phosphonates, we have focused our research on the relatively unexplored methylborane phosphine (Me-P-BH3) modification. This Article describes the automated solid-phase synthesis of mixed-backbone oligodeoxynu-cleotides (ODNs) consisting of methylborane phosphine and phosphate or thiophosphate linkages (16-mers). Nuclease stability assays show that methylborane phosphine ODNs are highly resistant to 5' and 3' exonucleases. When hybridized to a complementary strand, the ODN:RNA duplex was more stable than its corresponding ODN:DNA duplex. The binding affinity of ODNANA duplex increased at lower salt concentration and approached that of a native DNA:RNA duplex under conditions close to physiological saline, indicating that the Me-P-BH3 linkage is positively charged. Cellular uptake measurements indicate that these ODNs are efficiently taken up by cells even when the strand is 13% modified. Treatment of HeLa cells and WM-239A cells with fluorescently labeled ODNs shows significant cytoplasmic fluorescence when viewed under a microscope. Our results suggest that methylborane phosphine ODNs may prove very valuable as potential candidates in antisense research and RNAi.

  DOI：

  10.1021/ja201314q

文献信息

• Extended Length Borane Phosphonate Nucleic Acid Compounds
  申请人：McCuen Heather Brummel

  公开号：US20100010069A1

  公开（公告）日：2010-01-14

  The present invention provides a novel method for solid-phase phosphoramidite based synthesis of borane phosphonate DNA. Also provided are novel phosphoramidite molecules, novel extended length borane phosphonate nucleic acid compounds, and methods of use thereof.

  本发明提供了一种新颖的固相磷酰胺酯基合成硼磷酸酯DNA的方法。还提供了新颖的磷酰胺酯分子、新颖的扩展长度的硼磷酸酯核酸化合物以及其使用方法。
• Synthesis And Biological Activity of Borane Phosphonate DNA
  作者：Magdalena Olesiak、Angelika Krivenko、Heera Krishna、Marvin H. Caruthers

  DOI：10.1080/10426507.2010.538456

  日期：2011.3.31

  complete synthesis of the oligodeoxyribonucleotide phosphite triester, oxidation with THF·BH3 yields the oligodeoxyribonucleotide borane phosphonate. Further treatment with 80% aqueous acetic acid followed by disodium 2-carbamoyl-2-cyanoethylene-1,1-dithiolate removes trimethoxytrityl from the 2′-deoxyribonucleoside bases and the methyl protecting group from the internucleotide phosphate triester,

  摘要 硼烷膦酸酯寡脱氧核糖核苷酸由 5'-O-[苯羟基双（三甲基甲硅烷氧基）甲硅烷基]-2'-脱氧核糖核苷-3'-O-甲基亚磷酰胺合成。腺嘌呤、鸟嘌呤和胞嘧啶的环外胺功能受三甲氧基三苯甲基保护，而胸腺嘧啶不受保护。使用这些合成子并在标准条件下通过 S-乙基硫代四唑活化，高度交联的聚苯乙烯载体上的缩合超过 99%。在寡脱氧核糖核苷酸亚磷酸三酯完全合成后，用 THF·BH3 氧化产生寡脱氧核糖核苷酸硼烷膦酸酯。用 80% 乙酸水溶液进一步处理，然后用 2-氨基甲酰基-2-氰基乙烯-1 二钠处理，1-dithiolate 分别从 2'-脱氧核糖核苷碱基和核苷酸间磷酸三酯中的甲基保护基团中去除三甲氧基三苯甲基。用氢氧化铵从载体上裂解并通过反相 HPLC 纯化，得到纯的寡脱氧核糖核苷酸硼烷膦酸酯。这些寡聚体在没有阳离子脂质的情况下被细胞吸收，并将具有生物活性的干扰 RNA 转运到细胞中。