(1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(5-iodoracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane | 1202937-23-2

• 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: (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(5-iodoracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: 1-[(1R,3R,4R,7S)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-5-iodopyrimidine-2,4-dione
• CAS: 1202937-23-2
• 化学式: C₃₁H₂₉IN₂O₈
• 分子量: 684.484
• InChiKey: GUNSOPLNNQVGJE-GGLVTHGASA-N

物化性质

• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(5-iodoracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 copper(l) iodide 、 四(三苯基膦)钯 、 四丁基氟化铵 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (1R,3R,4R,7S)-7-[2-cyanoethoxy(diisopropylamino)phosphinoxy]-1-(4,4′-dimethoxytrityloxymethyl)-3-(5-ethynyluracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

  摘要：

  Oligonucleotides modified with conformationally restricted nucleotides such as locked nucleic acid (LNA) monomers are used extensively in molecular biology and medicinal chemistry to modulate gene expression at the RNA level. Major efforts have been devoted to the design of LNA derivatives that induce even higher binding affinity and specificity, greater enzymatic stability, and more desirable pharmacokinetic profiles. Most of this work has focused on modifications of LNA's oxymethylene bridge. Here, we describe an alternative approach for modulation of the properties of LNA: i.e., through functionalization of LNA nucleobases. Twelve structurally diverse CS-functionalized LNA uridine (U) phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides (ONs), which were then characterized with respect to thermal denaturation, enzymatic stability, and fluorescence properties. ONs modified with monomers that are conjugated to small alkynes display significantly improved target affinity, binding specificity, and protection against 3'-exonucleases relative to regular LNA. In contrast, ONs modified with monomers that are conjugated to bulky hydrophobic alkynes display lower target affinity yet much greater 3'-exonuclease resistance. ONs modified with C5-fluorophore-functionalized LNA-U monomers enable fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs). In concert, these properties render C5-functionalized LNA as a promising class of building blocks for RNA-targeting applications and nucleic acid diagnostics.

  DOI：

  10.1021/jo500614a
• 作为产物：
  描述：

  1-(2’-O,4-C-甲桥-BETA-D-呋喃核糖基)尿苷 在 吡啶 、 ammonium cerium (IV) nitrate 、 碘 作用下， 以 溶剂黄146 为溶剂， 反应 16.67h， 生成 (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(5-iodoracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

  摘要：

  Oligonucleotides modified with conformationally restricted nucleotides such as locked nucleic acid (LNA) monomers are used extensively in molecular biology and medicinal chemistry to modulate gene expression at the RNA level. Major efforts have been devoted to the design of LNA derivatives that induce even higher binding affinity and specificity, greater enzymatic stability, and more desirable pharmacokinetic profiles. Most of this work has focused on modifications of LNA's oxymethylene bridge. Here, we describe an alternative approach for modulation of the properties of LNA: i.e., through functionalization of LNA nucleobases. Twelve structurally diverse CS-functionalized LNA uridine (U) phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides (ONs), which were then characterized with respect to thermal denaturation, enzymatic stability, and fluorescence properties. ONs modified with monomers that are conjugated to small alkynes display significantly improved target affinity, binding specificity, and protection against 3'-exonucleases relative to regular LNA. In contrast, ONs modified with monomers that are conjugated to bulky hydrophobic alkynes display lower target affinity yet much greater 3'-exonuclease resistance. ONs modified with C5-fluorophore-functionalized LNA-U monomers enable fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs). In concert, these properties render C5-functionalized LNA as a promising class of building blocks for RNA-targeting applications and nucleic acid diagnostics.

  DOI：

  10.1021/jo500614a

文献信息

• Optimized DNA-targeting using triplex forming C5-alkynyl functionalized LNA
  作者：Sujay P. Sau、Pawan Kumar、Brooke A. Anderson、Michael E. Østergaard、Lee Deobald、Andrzej Paszczynski、Pawan K. Sharma、Patrick J. Hrdlicka

  DOI：10.1039/b917312a

  日期：——

  Triplex forming oligonucleotides (TFOs) modified with C5-alkynyl functionalized LNA (locked nucleic acid) monomers display extraordinary thermal affinity toward double stranded DNA targets, excellent discrimination of Hoogsteen-mismatched targets, and high stability against 3′-exonucleases.

  用 C5-炔基官能化 LNA（锁定核酸）单体修饰的三重形成寡核苷酸（TFO）对双链 DNA 靶标具有超强的热亲和力，对胡格氏错配靶标具有出色的识别能力，对 3′-外切酶具有高度稳定性。
• Increased duplex stabilization in porphyrin-LNA zipper arrays with structure dependent exciton coupling
  作者：Daniel G. Singleton、Rohanah Hussain、Giuliano Siligardi、Pawan Kumar、Patrick J. Hrdlicka、Nina Berova、Eugen Stulz

  DOI：10.1039/c5ob01681a

  日期：——

  LNA-porphyrin building blocks were used to create stable zipper-porphyrin DNA arrays, which were analysed in detail with CD spectroscopy and thermodynamic studies.

  使用LNA-卟啉建筑模块创建了稳定的拉链卟啉DNA阵列，并通过CD光谱和热力学研究进行了详细分析。
• C5‐Functionalized DNA, LNA, and α‐ <scp>L</scp> ‐LNA: Positional Control of Polarity‐Sensitive Fluorophores Leads to Improved SNP‐Typing
  作者：Michael E. Østergaard、Pawan Kumar、Bharat Baral、Dale C. Guenther、Brooke A. Anderson、F. Marty Ytreberg、Lee Deobald、Andrzej J. Paszczynski、Pawan K. Sharma、Patrick J. Hrdlicka

  DOI：10.1002/chem.201002109

  日期：2011.3.7

  detection of SNPs at non‐stringent conditions due to differential fluorescence emission of matched versus mismatched nucleic acid duplexes. Herein, the thermal denaturation and optical spectroscopic characteristics of monomer X are compared to the corresponding locked nucleic acid (LNA) and α‐L‐LNA monomers Y and Z. ONs modified with monomers Y or Z result in a) larger increases in fluorescence intensity

  单核苷酸多态性（SNP）是疾病遗传学和药物基因组学研究中的重要标志。由于匹配或错配核酸双链体的荧光发射差异，用5- [3-（1-吡喃羧酰胺基）丙炔基] -2 -'-脱氧尿苷单体X修饰的寡脱氧核糖核苷酸（ON）能够在非严格条件下检测SNP。在此，将单体X的热变性和光谱特性与相应的锁定核酸（LNA）和α‐ L ‐ LNA单体Y和Z进行比较。用单体Y或Z改性的ON导致）的荧光强度杂交时由于显着地较大的荧光发射量子产率（Φ较大增大到互补DNA，b）中形成更明亮的荧光双链体的˚F = 0.44-0.80）和芘消光系数，以及c）改进的光学歧视DNA靶标中的SNP数量。光谱学研究表明，单体X – Z的核碱基部分采用了反义和同义分别与匹配的和错配的靶杂交时的构象。因此，对极性敏感的1-吡喃并羧酰胺基荧光团位于极性大槽中或疏水双链体核心中，靠近淬灭的核碱基。计算表明，LNA和α‐ L ‐ LNA单体Y和Z的
• C5-azobenzene-functionalized locked nucleic acid uridine: isomerization properties, hybridization ability, and enzymatic stability
  作者：K. Morihiro、O. Hasegawa、S. Mori、S. Tsunoda、S. Obika

  DOI：10.1039/c5ob00477b

  日期：——

  C5-azobenzene-functionalized locked nucleic acid uridine (LNA-UAz) shows effective photo-isomerization properties, RNA-selective hybridization ability, and high enzymatic stability.

  C5-偶氮苯基化锁定核酸尿苷（LNA-UAz）表现出有效的光异构化性质、RNA选择性杂交能力和高酶稳定性。
• Carbohydrate-Functionalized Locked Nucleic Acids: Oligonucleotides with Extraordinary Binding Affinity, Target Specificity, and Enzymatic Stability
  作者：Mamta Kaura、Dale C. Guenther、Patrick J. Hrdlicka

  DOI：10.1021/ol501306u

  日期：2014.6.20

  Three different C5-carbohydrate-functionalized LNA uridine phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides. C5-Carbohydrate-functionalized LNA display higher affinity toward complementary DNA/RNA targets (ΔTm/modification up to +11.0 °C), more efficient discrimination of mismatched targets, and superior resistance against 3'-exonucleases compared to conventional LNA. These properties render C5-carbohydrate-functionalized LNAs as promising modifications in antisense technology and other nucleic acid targeting applications.