5'-O-[benzhydryloxy-bis(trimethylsilyloxy)silyl]-N4-(4,4',4"-trimethoxytrityl)-2'-deoxycytidine | 904291-41-4

• 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-[benzhydryloxy-bis(trimethylsilyloxy)silyl]-N4-(4,4',4"-trimethoxytrityl)-2'-deoxycytidine
• 英文别名: 5'-O-[benzhydroxy-bis(trimethylsilyloxy)silyl]-N4-(4,4',4''-trimethoxytrityl)-2'-deoxycytidine；benzhydryl [(2R,3S,5R)-3-hydroxy-5-[2-oxo-4-[tris(4-methoxyphenyl)methylamino]pyrimidin-1-yl]oxolan-2-yl]methyl bis(trimethylsilyl) silicate
• CAS: 904291-41-4
• 化学式: C₅₀H₆₁N₃O₁₀Si₃
• 分子量: 948.305
• InChiKey: XOUKGSIYLKBATF-QSQYQKHJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.28
• 重原子数：
  66
• 可旋转键数：
  20
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5'-O-[benzhydryloxy-bis(trimethylsilyloxy)silyl]-N4-(4,4',4"-trimethoxytrityl)-2'-deoxycytidine 、 bis(diisopropylamino)(methyl)phosphine 在 4,5-二氰基咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以45%的产率得到
  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
• 作为产物：
  描述：

  4-Amino-1-((2R,4S,5R)-4-trimethylsilanyloxy-5-trimethylsilanyloxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one 在 吡啶 、 咪唑 、 ammonium hydroxide 、 水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 5'-O-[benzhydryloxy-bis(trimethylsilyloxy)silyl]-N4-(4,4',4"-trimethoxytrityl)-2'-deoxycytidine
  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

• Synthesis and Biochemical Activity of New Oligonucleotide Analogs
  作者：Heather Brummel McCuen、Mary S. Noe、Magdalena Olesiak、Agnieszka B. Sierzchala、Marvin H. Caruthers、Adrian P. Higson

  DOI：10.1080/10426500701734745

  日期：2008.1.14

  tetrazole, condensations in excess of 99% are observed. Oxidation with either THF·BH3 or a peroxyanion solution followed by cleavage of the silyl ether with fluoride completes a cycle. Following synthesis of an appropriate oligomer, protecting groups are removed using sequentially acetic acid, a dithiolate and ammonium hydroxide. Oligodeoxynucleotide 10 mers and 12 mers having any combination of borane

  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。
• 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。
• Solid-Phase Synthesis, Thermal Denaturation Studies, Nuclease Resistance, and Cellular Uptake of (Oligodeoxyribonucleoside)methylborane Phosphine–DNA Chimeras
  作者：Heera Krishna、Marvin H. Caruthers

  DOI：10.1021/ja201314q

  日期：2011.6.29

  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.