1-[3-O-benzyl-2,5-di-O-(methylsulfonyl)-4-C-(methylsulfonyloxymethyl)-α-L-threo-pentofuranosyl]thymine | 296253-28-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[3-O-benzyl-2,5-di-O-(methylsulfonyl)-4-C-(methylsulfonyloxymethyl)-α-L-threo-pentofuranosyl]thymine
• 英文别名: 1-(3-O-benzyl-2,5-di-O-methanesulfonyl-4-C-(methanesulfonyloxymethyl)-β-D-xylofuranosyl)thymine；1-(3-O-benzyl-2,5-di-O-methanesulfonyl-4-C-(methansulfonyloxymethyl)-α-L-threo-pentofuranosyl)thymine；1-(3-O-Benzyl-2,5di-O-methanesulfonyl-4-C-(methanesulfonyloxymethyl)-β-D-xylofuranosyl)thymine；1-(3-O-Benzyl-2,5di-O-methanesulfonyl-4-C-(methanesulfonyloxymethyl)-beta-D-xylofuranosyl)thymine；[(3R,4R,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-methylsulfonyloxy-2-(methylsulfonyloxymethyl)-3-phenylmethoxyoxolan-2-yl]methyl methanesulfonate
• CAS: 296253-28-6
• 化学式: C₂₁H₂₈N₂O₁₃S₃
• 分子量: 612.657
• InChiKey: FGZFFVCJLAVVJY-ZHALLVOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  223
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  1-[3-O-benzyl-2,5-di-O-(methylsulfonyl)-4-C-(methylsulfonyloxymethyl)-α-L-threo-pentofuranosyl]thymine 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 15-冠醚-5 、 硫酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三甲基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 18.0h， 生成 (1R,3R,4R,7R)-1-(benzoyloxymethyl)-7-benzyloxy-3-(thymin-1-yl)-2-oxa-5-azabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Xylo-Configured oligonucleotides (XNA, xylo nucleic acid): synthesis of conformationally restricted derivatives and hybridization towards DNA and RNA complements

  摘要：

  Xylo-Configured oligonucleotides (XNA) containing a novel conformationally restricted 2'-deoxy-2'-fluoro-beta-D-xylofuranosyl nucleotide monomer, a novel conformationally locked 2'-amino-2'-deoxy-2'-N,4'-C-methylene-beta-D-xylofuranosyl nucleotide monomer. and a known 2'-deoxy-beta-D-xylofuranosyl nucleotide monomer (XNA monomers) have been synthesized and their hybridization towards DNA and RNA complements studied. Thermal denaturation studies of nine-mer mixed-base sequences composed of a mixture of XNA monomers and DNA monomers revealed preferential hybridization towards RNA complements relative to DNA complements. For 14-mer homo-thymine XNAs containing thirteen XNA monomers, stable complexes towards single-stranded DNA and RNA were formed at pH 7. Gel-shift experiments revealed these complexes to involve at least two XNA strands per DNA or RNA target strand. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00441-4
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 吡啶 、 三氟甲磺酸三甲基硅酯 、 氨 作用下， 以 甲醇 为溶剂， 生成 1-[3-O-benzyl-2,5-di-O-(methylsulfonyl)-4-C-(methylsulfonyloxymethyl)-α-L-threo-pentofuranosyl]thymine
  参考文献：
  名称：

  Xylo-Configured oligonucleotides (XNA, xylo nucleic acid): synthesis of conformationally restricted derivatives and hybridization towards DNA and RNA complements

  摘要：

  Xylo-Configured oligonucleotides (XNA) containing a novel conformationally restricted 2'-deoxy-2'-fluoro-beta-D-xylofuranosyl nucleotide monomer, a novel conformationally locked 2'-amino-2'-deoxy-2'-N,4'-C-methylene-beta-D-xylofuranosyl nucleotide monomer. and a known 2'-deoxy-beta-D-xylofuranosyl nucleotide monomer (XNA monomers) have been synthesized and their hybridization towards DNA and RNA complements studied. Thermal denaturation studies of nine-mer mixed-base sequences composed of a mixture of XNA monomers and DNA monomers revealed preferential hybridization towards RNA complements relative to DNA complements. For 14-mer homo-thymine XNAs containing thirteen XNA monomers, stable complexes towards single-stranded DNA and RNA were formed at pH 7. Gel-shift experiments revealed these complexes to involve at least two XNA strands per DNA or RNA target strand. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00441-4

文献信息

• Synthesis of locked nucleic acid derivatives
  申请人：——

  公开号：US20040014959A1

  公开（公告）日：2004-01-22

  The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as &agr;-L-oxy-LNA, amino-LNA, &agr;-L-amino-LNA, thio-LNA, &agr;-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues. 1

  该发明涉及一种用于合成锁定核酸衍生物的新策略，例如α-L-氧基-LNA、氨基-LNA、α-L-氨基-LNA、硫基-LNA、α-L-硫基-LNA、硒基-LNA和亚甲基-LNA，该策略利用中间体进行可扩展的高产率反应，这些中间体还可以产生其他LNA类似物，如氧基-LNA。另外，公式X的化合物是重要的中间体，可以与多种亲核试剂反应，生成各种LNA类似物。
• XNA (xylo Nucleic Acid): A Summary and New Derivatives
  作者：B. Ravindra Babu、Raunak、Nicolai E. Poopeiko、Martin Juhl、Andrew D. Bond、Virinder S. Parmar、Jesper Wengel

  DOI：10.1002/ejoc.200500023

  日期：2005.6

  furanose conformation. Besides, an efficient synthesis of known xylo-LNA phosphoramidite 19, required for the incorporation of 1-(2'-O,4'-C-methylene-β-D-xylofuranosyl)thymine (monomer L) is described. For comparison, hydridization data of various XNAs reported in the literature are included in the discussion section. The thermal denaturation studies show that XNAs containing conformationally locked

  完全修饰的同型嘧啶 2'-脱氧-木核酸 (dXNA) 与互补的 DNA/RNA 形成三螺旋，其热稳定性与相应的 DNA:DNA 和 DNA:RNA 双链体的热稳定性相当。然而，在 DNA 链中插入单个或几个 dXNA 单体会显着降低双链体的稳定性。已知 dXNA 单体在溶液中主要采用 N 型呋喃糖构象。为了提高结合亲和力，已经合成了七种糖修饰的 XNA 单体（H、F、N、M、K、P 和 Q），并研究了它们对 DNA 和 RNA 互补物杂交的影响。预计引入 2'-氟和 2'-羟基取代基会导致对衍生自 1-(2'-deoxy-2' 的单体 F 的 C3'-内型呋喃糖构象的构象限制 -氟-β-D-呋喃木糖基）胸腺嘧啶和衍生自 1-（β-D-呋喃木糖基）胸腺嘧啶的单体 H。存在面向小沟的官能团，如 1-(2'-amino-2'-deoxy-2'-N,4'-C-methylene-β-D-xylofuranosyl)thymine
• 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）。
• L-Ribo-LNA analogues
  申请人：——

  公开号：US20030087230A1

  公开（公告）日：2003-05-08

  Provided are L-ribo bicyclic nucleotide compounds as well as syntheses of such compounds The nucleoside compounds of the invention are useful in forming oligonucleotides that can produce nucleobase specific duplexes with complementary single stranded and double stranded nucleic acids.

  提供L-核苷酸双环化合物及其合成方法。本发明的核苷酸化合物可用于形成寡核苷酸，可与互补的单链和双链核酸产生核碱基特异性的双链。