(1S,3R,4S,7R)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptane | 245366-58-9

• 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: (1S,3R,4S,7R)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: 1-[(1S,3R,4S,7R)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-5-methylpyrimidine-2,4-dione
• CAS: 245366-58-9
• 化学式: C₃₂H₃₂N₂O₈
• 分子量: 572.615
• InChiKey: LRHODMQLNIWFSL-SDSXRCECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 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：

  (1S,3R,4S,7R)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 吡啶 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 1-[3-O-acetyl-5-O-(4,4'-dimethoxytrityl)-2-O,4-C-methylene-α-L-ribofuranosyl]-5-methyl-4-(1,2,4-triazol-1-yl)-2-oxypyrimidine
  参考文献：
  名称：

  Conformationally restricted triplex-forming oligonucleotides (TFOs). Binding properties of α-l-LNA and introduction of the N7-glycosylated LNA-guanosine

  摘要：

  The method for scaled-up production of alpha-L-LNA phosphoramidite building blocks containing thymine and 5-methylcytosine nucleobases is described. Binding properties of pyrimidine TFOs modified with alpha-L-LNA are reported. In contrast to LNA TFOs, the fully modified a-L-LNA forms a stable triplex with a model DNA duplex. Pyrimidine DNA/LNA/alpha-L-LNA chimeras also efficiently hybridize with a model DNA duplex in the parallel mode. LNA nucleoside containing unnatural N-7-glycosylated guanine (LNA-(7) G) was synthesized by a convergent method and incorporated into LNA oligonucleotides. The triplex-forming alternating DNA/LNA oligonucleotides containing a single LNA-(7) G modification instead of internal LNA-mC demonstrate improved pH-dependent properties. The single LNA-(7) G modification can also discriminatively reduce competitive binding of TFOs to natural nucleic acids in the antiparallel duplex mode. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.04.016
• 作为产物：
  描述：

  3-O-benzyl-5-O-(methanesulfonyl)-4-C-[[(methanesulfonyl)oxy]methyl]-1,2-O-isopropylidene-β-L-threo-pentofuranose 在 palladium dihydroxide 吡啶 、 盐酸 、 sodium hydroxide 、 N,O-双三甲硅基乙酰胺 、 硫酸 、 甲酸铵 、 溶剂黄146 、 苯甲醇钠 作用下， 以 1,4-二氧六环 、 甲醇 、 二甲基亚砜 、 乙腈 为溶剂， 反应 56.0h， 生成 (1S,3R,4S,7R)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Conformationally restricted triplex-forming oligonucleotides (TFOs). Binding properties of α-l-LNA and introduction of the N7-glycosylated LNA-guanosine

  摘要：

  The method for scaled-up production of alpha-L-LNA phosphoramidite building blocks containing thymine and 5-methylcytosine nucleobases is described. Binding properties of pyrimidine TFOs modified with alpha-L-LNA are reported. In contrast to LNA TFOs, the fully modified a-L-LNA forms a stable triplex with a model DNA duplex. Pyrimidine DNA/LNA/alpha-L-LNA chimeras also efficiently hybridize with a model DNA duplex in the parallel mode. LNA nucleoside containing unnatural N-7-glycosylated guanine (LNA-(7) G) was synthesized by a convergent method and incorporated into LNA oligonucleotides. The triplex-forming alternating DNA/LNA oligonucleotides containing a single LNA-(7) G modification instead of internal LNA-mC demonstrate improved pH-dependent properties. The single LNA-(7) G modification can also discriminatively reduce competitive binding of TFOs to natural nucleic acids in the antiparallel duplex mode. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.04.016

文献信息

• Preparation of LNA Phosphoramidites
  作者：Daniel Sejer Pedersen、Christoph Rosenbohm、Troels Koch

  DOI：10.1055/s-2002-25756

  日期：——

  A highly efficient method for the preparation of LNA (Locked Nucleic Acid) phosphoramidite monomers with 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite and 4,5-dicyanoimidazole has been devised. The quality of the phosphoramidites prepared in this manner is equal to HPLC purified phosphoramidites and can easily be used for oligonucleotide synthesis without further purification. In addition the possibility of using 4,5-dicyanoimidazole in catalytic amounts has been investigated and showed optimum results when 0.7 equivalent was used, and that reducing the amount further leads to undesired phosphitylation of the nucleobase.Furthermore it is demonstrated that LNA phosphoramidite monomers are exceedingly stable in acetonitrile solution thereby prolonging the effective lifetime of the reagent significantly.

  已设计出一种高效制备LNA（锁核酸）磷酰胺单体的方法，该方法使用2-氰乙基-N,N,N',N'-四异丙基磷酸二酰胺和4,5-二氰基咪唑。以此方式制备的磷酰胺质量与HPLC纯化的磷酰胺相当，无需进一步纯化即可轻松用于寡核苷酸合成。此外，研究了使用催化量的4,5-二氰基咪唑的可能性，并发现当使用0.7当量时获得最佳结果，而进一步减少用量会导致核苷碱基的不希望的磷酸化。此外，实验证明LNA磷酰胺单体在乙腈溶液中极为稳定，从而显著延长了试剂的有效使用寿命。
• α-<scp>l</scp>-<i>ribo</i>-Configured Locked Nucleic Acid (α-L-LNA):  Synthesis and Properties
  作者：Mads D. Sørensen、Lisbet Kværnø、Torsten Bryld、Anders E. Håkansson、Birgit Verbeure、Gilles Gaubert、Piet Herdewijn、Jesper Wengel

  DOI：10.1021/ja0168763

  日期：2002.3.1

  The syntheses of monomeric nucleosides and 3‘-O-phosphoramidite building blocks en route to α-l-ribo-configured locked nucleic acids (α-L-LNA), composed entirely of α-L-LNA monomers (α-l-ribo configuration) or of a mixture of α-L-LNA and DNA monomers (β-d-ribo configuration), are described and the α-L-LNA oligomers are studied. Bicyclic 5-methylcytosin-1-yl and adenin-9-yl nucleoside derivatives have

  单体核苷和 3'-O-亚磷酰胺结构单元的合成在生成 α-l-核糖构型锁核酸 (α-L-LNA) 的过程中，完全由 α-L-LNA 单体（α-l-核糖核酸）组成构型）或 α-L-LNA 和 DNA 单体的混合物（β-d-核糖构型），进行了描述，并研究了 α-L-LNA 低聚物。已制备双环 5-甲基胞嘧啶-1-基和腺嘌呤-9-基核苷衍生物，亚磷酰胺方法已用于自动寡聚化，从而产生 α-L-LNA 寡聚体。结合研究表明可以非常有效地识别单链 DNA 和 RNA 靶寡核苷酸链。因此，包含 α-L-LNA 单体和 DNA 单体混合物（“mix-mer α-L-LNA”）的立体不规则 α-L-LNA 11-mers 显示每次修改的 ΔTm 值为 +1 至 +3 °C与相应的未修饰 DNA·DNA 和 DNA·RNA 参考双链体相比，DNA 和 +4 至 +5°C 的 RNA。立体规则 f 每次修改的相应
• Convenient Syntheses of 7-Hydroxy-1-(hydroxymethyl)- 3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptanes:  α-<scp>l</scp>-Ribo- and α-<scp>l</scp>-Xylo-Configured LNA Nucleosides
  作者：Anders E. Håkansson、Alexei A. Koshkin、Mads D. Sørensen、Jesper Wengel

  DOI：10.1021/jo000232g

  日期：2000.8.1

  Synthesis of the diastereoisomeric LNA (locked nucleic acid) nucleosides 1-(2-O,4-C-methylene-alpha-L-ribofuranosyl)thymine (6) and 1-(2-O,4-C-methylene-alpha-L-xylofuranosyl)thymine (13) are reported via convenient reaction cascades from di-O-p-toluenesulfonyl and tri-O-methanesulfonyl nucleoside derivatives 3, 7, and 10.

  非对映异构LNA（锁核酸）核苷1-（2-O，4-C-亚甲基-α-L-呋喃呋喃糖基）胸腺嘧啶（6）和1-（2-O，4-C-亚甲基-α-通过二-对-甲苯磺酰基和三-O-甲磺酰基核苷衍生物3、7和10的便捷反应级联报道了L-木呋喃糖基）胸腺嘧啶（13）。
• LNA stereoisomers: xylo-LNA (β-D-xylo configured locked nucleic acid) and α-L-LNA (α-L-ribo configured locked nucleic acid)
  作者：Vivek K. Rajwanshi、Anders E. Håkansson、Britta M. Dahl、Jesper Wengel

  DOI：10.1039/a903189h

  日期：——

  Synthesis of xylo-LNA containing one 2′-O,4′-C-methylene-β-D-xylofuranosyl thymine nucleotide monomer and α-L-LNAs containing one or four 2′-O,4′-C-methylene-α-L-ribofuranosyl thymine nucleotide monomer(s) has been accomplished using phosphoramidite chemistry with pyridine hydrochloride as activator; oligothymidylate α-L-LNA displays strongly enhanced affinity towards complementary RNA.

  以盐酸吡啶为活化剂，利用磷酰胺化学法合成了含有一个 2â²-O,4â²-C-亚甲基-δ-D-呋喃甲酰胸腺嘧啶核苷酸单体的 xylo-LNA 和含有一个或四个 2â²-O,4â²-C-亚甲基-δ-L-呋喃甲酰胸腺嘧啶核苷酸单体的 δ-LNA；寡胸苷酸δ±-L-LNA 对互补 RNA 的亲和力大大增强。