(R)-2-[(R)-1-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-oxo-ethoxy]-3-[(4-methoxy-phenyl)-diphenyl-methoxy]-propionaldehyde | 537041-04-6

• 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: (R)-2-[(R)-1-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-oxo-ethoxy]-3-[(4-methoxy-phenyl)-diphenyl-methoxy]-propionaldehyde
• 英文别名: (2R)-2-[(1R)-1-(2,4-dioxopyrimidin-1-yl)-2-oxoethoxy]-3-[(4-methoxyphenyl)-diphenylmethoxy]propanal
• CAS: 537041-04-6
• 化学式: C₂₉H₂₆N₂O₇
• 分子量: 514.535
• InChiKey: HLDQDSWAQAXAMS-AHKZPQOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-2-[(R)-1-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-oxo-ethoxy]-3-[(4-methoxy-phenyl)-diphenyl-methoxy]-propionaldehyde 在 甲醇 、 tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene](benzylidene)Ru(II) dichloride 、 正丁基锂 、 12-冠醚-4 、 Dowex 50W 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 52.0h， 生成 2’,3’-二脱氢-2’,3’-二脱氧尿苷
  参考文献：
  名称：

  通过烯烃复分解反应通过 2',3'-Diyne seco 类似物直接合成标记和未标记的嘧啶 d4Ns

  摘要：

  从核苷合成双脱氧核苷 (ddNs) 或双脱氢-双脱氧核苷 (d4Ns) 已被广泛审查。虽然之前描述的方法是基于完整核糖部分的 2'-和/或 3'-OH 基团的修饰，但使用闭环复分解 (RCM) 来形成核苷的不饱和环状系统可以是 d4Ns 的直接方法。因此，作为我们药物标签计划的一部分，本文报告了 2',3'-didehydro-2',3'-dideoxyuridine (d4U) 和 [1',2',3',4',5 '-13C5,6-13C,1,3-15N2]d4T 使用 RCM 协议。本文讨论了核苷二烯的制备和钌基复分解催化剂的活性。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

  DOI：

  10.1002/ejoc.200390107
• 作为产物：
  描述：

  5'-O-monomethoxytrityluridine 在 sodium periodate 作用下， 以 1,4-二氧六环 为溶剂， 生成 (R)-2-[(R)-1-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-oxo-ethoxy]-3-[(4-methoxy-phenyl)-diphenyl-methoxy]-propionaldehyde
  参考文献：
  名称：

  Efficient RNase H-Directed Cleavage of RNA Promoted by Antisense DNA or 2‘F-ANA Constructs Containing Acyclic Nucleotide Inserts

  摘要：

  The ability of modified antisense oligonucleotides (AONs) containing acyclic interresidue units to support RNase H-promoted cleavage of complementary RNA is described. Manipulation of the backbone and sugar geometries in these conformationally labile monomers shows great benefits in the enzymatic recognition of the nucleic acid hybrids, while highlighting the importance of local strand conformation on the hydrolytic efficiency of the enzyme more conclusively. Our results demonstrate that the duplexes support remarkably high levels of enzymatic degradation when treated with human RNase Hit, making them efficient mimics of the native substrates. Furthermore, interesting linker-dependent modulation of enzymatic activity is observed during in vitro assays, suggesting a potential role for this AON class in an RNase H-dependent pathway of controlling RNA expression, Additionally, the butyl-modified 2'F-ANA AONs described in this work constitute the first examples of a nucleic acid species capable of eliciting high RNase H activity while possessing a highly flexible molecular architecture at predetermined sites along the AON.

  DOI：

  10.1021/ja025557o

文献信息

• Efficient RNase H-Directed Cleavage of RNA Promoted by Antisense DNA or 2‘F-ANA Constructs Containing Acyclic Nucleotide Inserts
  作者：Maria M. Mangos、Kyung-Lyum Min、Ekaterina Viazovkina、Annie Galarneau、Mohamed I. Elzagheid、Michael A. Parniak、Masad J. Damha

  DOI：10.1021/ja025557o

  日期：2003.1.1

  The ability of modified antisense oligonucleotides (AONs) containing acyclic interresidue units to support RNase H-promoted cleavage of complementary RNA is described. Manipulation of the backbone and sugar geometries in these conformationally labile monomers shows great benefits in the enzymatic recognition of the nucleic acid hybrids, while highlighting the importance of local strand conformation on the hydrolytic efficiency of the enzyme more conclusively. Our results demonstrate that the duplexes support remarkably high levels of enzymatic degradation when treated with human RNase Hit, making them efficient mimics of the native substrates. Furthermore, interesting linker-dependent modulation of enzymatic activity is observed during in vitro assays, suggesting a potential role for this AON class in an RNase H-dependent pathway of controlling RNA expression, Additionally, the butyl-modified 2'F-ANA AONs described in this work constitute the first examples of a nucleic acid species capable of eliciting high RNase H activity while possessing a highly flexible molecular architecture at predetermined sites along the AON.
• Straightforward Synthesis of Labeled and Unlabeled Pyrimidine d4Ns via 2′,3′-Diyne seco Analogues through Olefin Metathesis Reactions
  作者：Isabelle Gillaizeau、Irene M. Lagoja、Steve P. Nolan、Vincent Aucagne、Jef Rozenski、Piet Herdewijn、Luigi A. Agrofoglio

  DOI：10.1002/ejoc.200390107

  日期：2003.2

  The synthesis of dideoxynucleosides (ddNs) or didehydro-dideoxynucleosides (d4Ns) from nucleosides has been extensively reviewed. While previously described methods are based on the modification of the 2′- and/or 3′-OH group of the intact ribose moiety, the use of a ring-closing metathesis (RCM) for the formation of the unsaturated cyclic system of nucleosides could be a straightforward approach to

  从核苷合成双脱氧核苷 (ddNs) 或双脱氢-双脱氧核苷 (d4Ns) 已被广泛审查。虽然之前描述的方法是基于完整核糖部分的 2'-和/或 3'-OH 基团的修饰，但使用闭环复分解 (RCM) 来形成核苷的不饱和环状系统可以是 d4Ns 的直接方法。因此，作为我们药物标签计划的一部分，本文报告了 2',3'-didehydro-2',3'-dideoxyuridine (d4U) 和 [1',2',3',4',5 '-13C5,6-13C,1,3-15N2]d4T 使用 RCM 协议。本文讨论了核苷二烯的制备和钌基复分解催化剂的活性。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)