6-N-benzoyl-9-(3,5-O-bis-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl)adenine | 82434-61-5

• 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: 6-N-benzoyl-9-(3,5-O-bis-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl)adenine
• 英文别名: N-[9-[(2R,3R,4S,5R)-4-[bis(4-methoxyphenyl)-phenylmethoxy]-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-hydroxyoxolan-2-yl]purin-6-yl]benzamide
• CAS: 82434-61-5
• 化学式: C₅₉H₅₃N₅O₉
• 分子量: 976.098
• InChiKey: LQQDJZDHCHXYDI-QUHJFTIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  73
• 可旋转键数：
  18
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  6-N-benzoyl-9-(3,5-O-bis-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl)adenine 在 吡啶 、 sodium hydride 、 溶剂黄146 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 diisopropyl [3-O-benzoyl-1-(6-N-benzoyladenin-9-yl)-5-O-(4,4'-dimethoxytrityl)-β-D-ribofuranos-2-O-yl]methylphosphonate
  参考文献：
  名称：

  Activation of Murine RNase L by Isopolar 2‘-Phosphonate Analogues of 2‘,5‘ Oligoadenylates

  摘要：

  To determine the influence of methylene group insertion in the internucleotide linkage on the binding process of 2', 5'-oligoadenylates to RNase L, a series of 2'-phosphonate-modified trimers and tetramers were synthesized from appropriate monomeric units and evaluated for their ability to bind to murine RNase L. Tetramers pAAXA modified by ribo-, arabino-, or xylo-2'-phosphonate unit X in the third position were capable of binding to RNase L in nanomolar concentrations. The replacement of the first residue ( pXAAA), or both the first and the third residues ( pXAXA), was also tolerated by the enzyme. In contrast, in all cases, the replacement of the second residue ( pAXAA) resulted in the significant decrease of binding ability. Additionally, no more than two phosphonate modifications in the tetramer were allowed to retain the binding affinity to the enzyme. Although all three tetramers pAAXA were found to be potent enzyme binders, only tetramers modified by ribo- and xylo-2'-phosphonate unit X activated the RNase L-catalyzed cleavage of the RNA substrate. Surprisingly, tetramer pAAXA, modified by arabino-2'-phosphonate unit X, did not activate the enzyme and can be considered a potent antagonist. In comparison with their natural counterpart, the phosphonate analogues of the pA(4) exhibit superior resistance toward nucleases present in the murine spleen homogenate.

  DOI：

  10.1021/jm050401v
• 作为产物：
  描述：

  4,4'-双甲氧基三苯甲基氯 、 N6-苯甲酰基腺苷 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 生成 6-N-benzoyl-9-(3,5-O-bis-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  Ribo-,Xylo-, andArabino-Configured Adenine-Based Nucleoside Phosphonates: Synthesis of Monomers for Solid-Phase Oligonucleotide Assembly

  摘要：

  Adenine-based, regioisomeric nucleoside phosphonates with ribo, xylo and arabino configuration were synthesized in the protected form suitable for the phosphotriester-like, solid-phase synthesis of oligonucleotides. Phosphonate moiety was protected by 4-methoxy-1-oxido-2-picolyl group and the furanose hydroxyl by the dimethoxytrityl group.

  DOI：

  10.1081/ncn-120022734

文献信息

• New catalysts and procedures for the dimethoxytritylation and selective silylation of ribonucleosides
  作者：Gholam H. Hakimelahi、Zbigniew A. Proba、Kelvin K. Ogilvie

  DOI：10.1139/v82-165

  日期：1982.5.1

  Procedures have been developed for the selective formation of (a) 2′,5′-silylated ribonucleosides and (b) 3′,5′-silylated ribonucleosides. These procedures also permit the selective silylation at either the 2′- or 3′-position of dimethoxytritylated ribonucleosides. The procedures involve nitrate or perchlorate ion catalysis for selective reaction at 2′-positions and a combination of silver ion and DABCO or 4-nitropyridine N-oxide for selective reaction at the 3′-position. During the course of this work a general and rapid procedure was developed for the preparation and isolation of the 5′-dimethoxytrityl derivatives of the four common ribonucleosides. Silver ion was found to have a marked effect on dimethoxytritylation reactions.

  已开发出用于选择性形成2′,5′-硅烷基化核糖核苷和3′,5′-硅烷基化核糖核苷的程序。这些程序还允许在二甲氧基三苯甲基化核糖核苷的2′-或3′-位置进行选择性硅烷基化。这些程序涉及硝酸盐或高氯酸盐离子催化，用于在2′-位置进行选择性反应，以及银离子和DABCO或4-硝基吡啶-N-氧化物的组合，用于在3′-位置进行选择性反应。在这项工作过程中，开发了一种用于制备和分离四种常见核糖核苷的5′-二甲氧基三苯甲基衍生物的通用和快速程序。发现银离子对二甲氧基三苯甲基化反应有显着影响。
• Lekschas, Joerg; Cech, Dieter; Rosenthal, Andre, Zeitschrift fur Chemie, 1984, vol. 24, # 9, p. 329 - 330
  作者：Lekschas, Joerg、Cech, Dieter、Rosenthal, Andre

  DOI：——

  日期：——
• <i>Ribo</i>-,<i>Xylo</i>-, and<i>Arabino</i>-Configured Adenine-Based Nucleoside Phosphonates: Synthesis of Monomers for Solid-Phase Oligonucleotide Assembly
  作者：Ondřej Páv、Miloš Buděšínský、Ivan Rosenberg

  DOI：10.1081/ncn-120022734

  日期：2003.10

  Adenine-based, regioisomeric nucleoside phosphonates with ribo, xylo and arabino configuration were synthesized in the protected form suitable for the phosphotriester-like, solid-phase synthesis of oligonucleotides. Phosphonate moiety was protected by 4-methoxy-1-oxido-2-picolyl group and the furanose hydroxyl by the dimethoxytrityl group.
• Activation of Murine RNase L by Isopolar 2‘-Phosphonate Analogues of 2‘,5‘ Oligoadenylates
  作者：Ondrej Pav、Eva Protivinska、Martina Pressova、Michaela Collinsova、Jiri Jiracek、Jan Snasel、Milena Masojidkova、Milos Budesinsky、Ivan Rosenberg

  DOI：10.1021/jm050401v

  日期：2006.6.1

  To determine the influence of methylene group insertion in the internucleotide linkage on the binding process of 2', 5'-oligoadenylates to RNase L, a series of 2'-phosphonate-modified trimers and tetramers were synthesized from appropriate monomeric units and evaluated for their ability to bind to murine RNase L. Tetramers pAAXA modified by ribo-, arabino-, or xylo-2'-phosphonate unit X in the third position were capable of binding to RNase L in nanomolar concentrations. The replacement of the first residue ( pXAAA), or both the first and the third residues ( pXAXA), was also tolerated by the enzyme. In contrast, in all cases, the replacement of the second residue ( pAXAA) resulted in the significant decrease of binding ability. Additionally, no more than two phosphonate modifications in the tetramer were allowed to retain the binding affinity to the enzyme. Although all three tetramers pAAXA were found to be potent enzyme binders, only tetramers modified by ribo- and xylo-2'-phosphonate unit X activated the RNase L-catalyzed cleavage of the RNA substrate. Surprisingly, tetramer pAAXA, modified by arabino-2'-phosphonate unit X, did not activate the enzyme and can be considered a potent antagonist. In comparison with their natural counterpart, the phosphonate analogues of the pA(4) exhibit superior resistance toward nucleases present in the murine spleen homogenate.