1-[3-O-benzyl-5-O-(methylsulfonyl)-4-C-(methylsulfonyloxymethyl)-α-L-erythro-pentofuranosyl]thymine | 601512-84-9

• 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-5-O-(methylsulfonyl)-4-C-(methylsulfonyloxymethyl)-α-L-erythro-pentofuranosyl]thymine
• 英文别名: [(3R,4S,5R)-4-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-(methylsulfonyloxymethyl)-3-phenylmethoxyoxolan-2-yl]methyl methanesulfonate
• CAS: 601512-84-9
• 化学式: C₂₀H₂₆N₂O₁₁S₂
• 分子量: 534.565
• InChiKey: KGOUDEBGIAOXFH-LZLYRXPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  192
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1-[3-O-benzyl-5-O-(methylsulfonyl)-4-C-(methylsulfonyloxymethyl)-α-L-erythro-pentofuranosyl]thymine 在 palladium dihydroxide 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 7.0h， 以92%的产率得到1-[5'-O-methanesulfonyl-4'-C-methanesulfonyloxymethyl-α-L-erythro-pentofuranosyl]thymine
  参考文献：
  名称：

  构象受限的3'-O，4'-C-亚甲基连接的α-1-核糖核苷酸的合成，核酸杂交性质和分子模型研究

  摘要：

  具有构象受限的碳水化合物环的核苷酸，例如锁核酸（LNA），α-L-LNA或2'，5'-连接的3'-O，4'-C-甲基核糖核苷酸，具有显着的潜力，可作为抗原和反义策略的基础。2'，5'-连接的α-L-核糖构型的单体X（称为α-L-ONA）被设计为α-L-LNA的潜在结构模拟物。从容易获得的胸腺嘧啶衍生物1中，以五个步骤（总收率10％）获得了相应的单体X的亚磷酰胺结构单元。将单体X掺入寡脱氧核糖核苷酸（ONs）中会使DNA / RNA补体（DeltaTm /与未修改的参考ON相比，mod = -11.5到-17.0摄氏度）。下降幅度较小（DeltaTm / mod = -4.5至-8。当将单体X掺入形成三链体的ONs中并靶向双链DNA（平行取向，嘧啶基序）时，观察到5摄氏度）。该生物物理数据以及建模研究表明，与2'，5'相连的α-L-ONA不能很好地模拟α-L-LNA。

  DOI：

  10.1016/j.carres.2006.04.010
• 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 、 硫酸 、 氨 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 丙酮 、 乙腈 为溶剂， 生成 1-[3-O-benzyl-5-O-(methylsulfonyl)-4-C-(methylsulfonyloxymethyl)-α-L-erythro-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

• 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
• Xylo-Configured oligonucleotides (XNA, xylo nucleic acid): synthesis of conformationally restricted derivatives and hybridization towards DNA and RNA complements
  作者：Nicolai E. Poopeiko、Martin Juhl、Birte Vester、Mads D. Sørensen、Jesper Wengel

  DOI：10.1016/s0960-894x(03)00441-4

  日期：2003.7

  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.
• Synthesis, nucleic acid hybridization properties and molecular modelling studies of conformationally restricted 3′-O,4′-C-methylene-linked α-l-ribonucleotides
  作者：Andreas S. Madsen、Patrick J. Hrdlicka、T. Santhosh Kumar、Jesper Wengel

  DOI：10.1016/j.carres.2006.04.010

  日期：2006.7

  des exhibit significant potential as building blocks for antigene and antisense strategies. 2',5'-Linked alpha-L-ribo configured monomer X (termed alpha-L-ONA) was designed as a potential structural mimic of alpha-L-LNA. The corresponding phosphoramidite building block of monomer X was obtained in five steps (10% overall yield) from the easily obtainable thymine derivative 1. Incorporation of monomer

  具有构象受限的碳水化合物环的核苷酸，例如锁核酸（LNA），α-L-LNA或2'，5'-连接的3'-O，4'-C-甲基核糖核苷酸，具有显着的潜力，可作为抗原和反义策略的基础。2'，5'-连接的α-L-核糖构型的单体X（称为α-L-ONA）被设计为α-L-LNA的潜在结构模拟物。从容易获得的胸腺嘧啶衍生物1中，以五个步骤（总收率10％）获得了相应的单体X的亚磷酰胺结构单元。将单体X掺入寡脱氧核糖核苷酸（ONs）中会使DNA / RNA补体（DeltaTm /与未修改的参考ON相比，mod = -11.5到-17.0摄氏度）。下降幅度较小（DeltaTm / mod = -4.5至-8。当将单体X掺入形成三链体的ONs中并靶向双链DNA（平行取向，嘧啶基序）时，观察到5摄氏度）。该生物物理数据以及建模研究表明，与2'，5'相连的α-L-ONA不能很好地模拟α-L-LNA。