diisopropyl [1-(6-N-benzoyladenin-9-yl)-β-D-ribofuranos-2-O-yl]methylphosphonate | 903882-56-4

• 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: diisopropyl [1-(6-N-benzoyladenin-9-yl)-β-D-ribofuranos-2-O-yl]methylphosphonate
• 英文别名: N-[9-[(2R,3R,4R,5R)-3-[di(propan-2-yloxy)phosphorylmethoxy]-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]benzamide
• CAS: 903882-56-4
• 化学式: C₂₄H₃₂N₅O₈P
• 分子量: 549.521
• InChiKey: BEVXLRTUYHHZRW-AGFSROSKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  167
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  diisopropyl [1-(6-N-benzoyladenin-9-yl)-β-D-ribofuranos-2-O-yl]methylphosphonate 在 吡啶 、 三乙胺 作用下， 以 乙腈 为溶剂， 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：

  (二异丙氧基磷酰)甲基对甲苯磺酸酯 在 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 diisopropyl [1-(6-N-benzoyladenin-9-yl)-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

文献信息

• <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.