3'-O-(N,N-diisopropylamino-2-cyanoethoxyphosphinyl)-5-(1-phenyl-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine | 1050649-10-9

• 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: 3'-O-(N,N-diisopropylamino-2-cyanoethoxyphosphinyl)-5-(1-phenyl-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine
• 英文别名: 3'-O-(P-2-cyanoethyl-N,N-diisopropylaminophosphinyl)-5'-O-(4,4′-dimethoxytrityl)-5-(1-phenyl-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine；3-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-[2,4-dioxo-5-(1-phenyltriazol-4-yl)pyrimidin-1-yl]oxolan-3-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• CAS: 1050649-10-9
• 化学式: C₄₇H₅₂N₇O₈P
• 分子量: 873.946
• InChiKey: CFBTYDQUQNUZHF-FNVIBMMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  63
• 可旋转键数：
  19
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  163
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2'-deoxy-5'-O-(4,4'-dimethoxytrityl)-5-ethynyluridine 在 吡啶 、 copper(ll) sulfate pentahydrate 、 二异丙基铵盐四氮唑 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 、 1,2-二氯乙烷 、 叔丁醇 为溶剂， 反应 19.0h， 生成 3'-O-(N,N-diisopropylamino-2-cyanoethoxyphosphinyl)-5-(1-phenyl-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine
  参考文献：
  名称：

  Increasing the Stability of DNA:RNA Duplexes by Introducing Stacking Phenyl-Substituted Pyrazole, Furan, and Triazole Moieties in the Major Groove

  摘要：

  Consecutive incorporations of our previously published thymidine analogue, 5-(1-pheny1-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W in oligonudeotides, has demonstrated significant duplex-stabilizing properties due to its efficient staking properties in the major groove of DNA:RNA duplexes. The corresponding 2'-deoxycytidine analogue is not as well-accommodated in duplexes, however, due to its clear preference for the ring-flipped coplanar conformation. In our present work, we have used oh initio calculations to design two new building blocks, 5-(5-phenylfuran-2-yl)-2'-deoxycytidine monomer Y and 5-(1-phenyl-1H-pyrazol-3-yl)-2'-deoxycytidine monomer Z, that emulate the conformation of W. These monomers were synthesized by Suzuki-Miyaura couplings, and the pyrazole moiety was obtained in a cycloaddition from N-phenylsydnone. We show that the novel analogues Y and Z engage in efficient stacking either with themselves or with W due to a better overlap of the aromatic moieties. Importantly, we demonstrate that this translates into very thermally stable DNA:RNA duplexes, thus making Y and especially Z good candidates for improving the binding affinities of oligonudeotide-based therapeutics. Since we now have both efficiently stacking T and C analogues in hand, any purine rich stretch can be effectively targeted using these simple analogues. Notably, we show that the introduction of the aromatic rings in the major groove does not significantly change the helical geometry.

  DOI：

  10.1021/acs.joc.5b01577

文献信息

• Synthesis and hybridization properties of oligonucleotides modified with 5-(1-aryl-1,2,3-triazol-4-yl)-2′-deoxyuridines
  作者：Mamta Kaura、Pawan Kumar、Patrick J. Hrdlicka

  DOI：10.1039/c2ob26717a

  日期：——

  Oligonucleotides modified with consecutive incorporations of 5-(1-aryl-1,2,3-triazol-4-yl)-2′-deoxyuridine monomers X–Z display strong thermal affinity and binding specificity toward RNA targets, due to formation of chromophore arrays in the major groove.

  连续掺入5-（1-芳基-1,2,3-三唑-4-基）-2'-脱氧尿苷单体X–Z修饰的寡核苷酸显示出很强的热亲和力和对RNA靶标的结合特异性，这是由于生色团的形成在主凹槽中排列。
• Efficient RNA-targeting by the introduction of aromatic stacking in the duplex major groove via 5-(1-phenyl-1,2,3-triazol-4-yl)-2′-deoxyuridines
  作者：Nicolai Krog Andersen、Navneet Chandak、Lucie Brulíková、Pawan Kumar、Michael Dalager Jensen、Frank Jensen、Pawan K. Sharma、Poul Nielsen

  DOI：10.1016/j.bmc.2010.05.019

  日期：2010.7

  Three pyrimidine nucleosides with differently substituted phenyltriazoles attached to the 5-position were prepared by Cu(I)-assisted azide-alkyne cycloadditions (CuAAC) and incorporated into oligonucleotides. Efficient pi-pi-stacking between two or more phenyltriazoles in the major groove was found to increase the thermal stability of a DNA: RNA duplex significantly. The best stacking, and most stable duplex, was obtained by a sulfonamide substituted derivative. (C) 2010 Elsevier Ltd. All rights reserved.
• Increasing the Stability of DNA:RNA Duplexes by Introducing Stacking Phenyl-Substituted Pyrazole, Furan, and Triazole Moieties in the Major Groove
  作者：Mick Hornum、Pawan Kumar、Patricia Podsiadly、Poul Nielsen

  DOI：10.1021/acs.joc.5b01577

  日期：2015.10.2

  Consecutive incorporations of our previously published thymidine analogue, 5-(1-pheny1-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W in oligonudeotides, has demonstrated significant duplex-stabilizing properties due to its efficient staking properties in the major groove of DNA:RNA duplexes. The corresponding 2'-deoxycytidine analogue is not as well-accommodated in duplexes, however, due to its clear preference for the ring-flipped coplanar conformation. In our present work, we have used oh initio calculations to design two new building blocks, 5-(5-phenylfuran-2-yl)-2'-deoxycytidine monomer Y and 5-(1-phenyl-1H-pyrazol-3-yl)-2'-deoxycytidine monomer Z, that emulate the conformation of W. These monomers were synthesized by Suzuki-Miyaura couplings, and the pyrazole moiety was obtained in a cycloaddition from N-phenylsydnone. We show that the novel analogues Y and Z engage in efficient stacking either with themselves or with W due to a better overlap of the aromatic moieties. Importantly, we demonstrate that this translates into very thermally stable DNA:RNA duplexes, thus making Y and especially Z good candidates for improving the binding affinities of oligonudeotide-based therapeutics. Since we now have both efficiently stacking T and C analogues in hand, any purine rich stretch can be effectively targeted using these simple analogues. Notably, we show that the introduction of the aromatic rings in the major groove does not significantly change the helical geometry.