1-[2,5-脱水-4-C-(羟甲基)-alpha-L-阿拉伯呋喃糖基]-2,4(1H,3H)-嘧啶二酮 | 1328937-93-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-[2,5-脱水-4-C-(羟甲基)-alpha-L-阿拉伯呋喃糖基]-2,4(1H,3H)-嘧啶二酮
• 英文名称: 2′-O,4′-C-methylenexylouridine
• 英文别名: 1-(2'O,4'C-methylene-β-D-xylofuranosyl)uracil；1-((1S,3R,4R,7R)-7-Hydroxy-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)pyrimidine-2,4(1H,3H)-dione；1-[(1S,3R,4R,7R)-7-hydroxy-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl]pyrimidine-2,4-dione
• CAS: 1328937-93-4
• 化学式: C₁₀H₁₂N₂O₆
• 分子量: 256.215
• InChiKey: KNLNWXXWKDEEFW-DQUBFYRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2',3',5'-tri-O-acetyl-4-C-p-toluenesulfonyloxymethyl-β-D-xylofuranosyluracil 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以95%的产率得到1-[2,5-脱水-4-C-(羟甲基)-alpha-L-阿拉伯呋喃糖基]-2,4(1H,3H)-嘧啶二酮
  参考文献：
  名称：

  酶促分离4-C-羟甲基化呋喃糖的异构体：双环核苷的合成。

  摘要：

  D-葡萄糖向4-C-羟甲基-1,2-O-异亚丙基-α-D-呋喃呋喃糖的转化是合成不同类型的双环/螺核苷的关键前体，导致了不可分离的形成所需产物与4-C-羟甲基-1，2-O-异亚丙基-α-D-木呋喃糖的1∶1混合物。已开发出一种方便环境的Novozyme®-435催化的选择性乙酰化方法，用于定量定量分离核糖基和木三羟基呋喃糖苷的差向异构体混合物。单乙酰化差向异构体的结构，即通过酶促乙酰化获得的5-O-乙酰基-4-C-羟甲基-1,2-O-异亚丙基-α-D-核糖-和木呋喃糖的结构已经通过X-确认。射线研究其相应的4-Cp-甲苯磺酰氧基甲基衍生物。此外，

  DOI：

  10.3762/bjoc.13.205

文献信息

• Xylo-LNA analogues
  申请人：——

  公开号：US20030082807A1

  公开（公告）日：2003-05-01

  Based on the above and on the remarkable properties of the 2 ′-O, 4 ′-C-methylene bridged LNA monomers it was decided to synthesise oligonucleotides comprising one or more 2 ′-O,′-C-methylene-&bgr;-D-xylofuranosyl nucleotide monomer(s) as the first stereoisomer of LNA modified oligonucleotides. Modelling clearly indicated the xylo-LNA monomers to be locked in an N-type furanose conformation. Whereas the parent 2 ′-deoxy-&bgr;-D-xylofuranosyl nucleosides were shown to adopt mainly an N-type furanose conformation, the furanose ring of the 2 ′-deoxy-&bgr;-D-xylofuranosyl monomers present in xylo-DNA were shown by conformational analysis and computer modelling to prefer an S-type conformation thereby minimising steric repulsion between the nucleobase and the 3 ′-O-phopshate group (Seela, F.; Wömer, Rosemeyer, H. Helv. Chem. Acta 1994, 77, 883 ). As no report on the hybridisation properties and binding mode of xylo-configurated oligonucleotides in an RNA context was believed to exist, it was the aim to synthesise 2 ′-O, 4 ′-C-methylene-&bgr;-D-xylofuranosyl nucleotide monomer and to study the thermal stability of oligonucleotides comprising this monomer. The results showed that fully modified or almost fully modified Xylo-LNA is useful for high-affinity targeting of complementary nucleic acids. When taking into consideration the inverted stereochemistry at C- 3 ′ this is a surprising fact. It is likely that Xylo-LNA monomers, in a sequence context of Xylo-DNA monomers, should have an affinity-increasing effect.

  基于上述和2′-O,4′-C-亚甲基桥联的LNA单体的显著特性，决定合成包含一个或多个2′-O,4′-C-亚甲基-&bgr;-D-木糖呋喃核苷单体的寡核苷酸，作为LNA修饰寡核苷酸的第一个立体异构体。建模清楚地表明，木糖-LNA单体被锁定在N-型呋喃糖环构象中。而父代2′-脱氧-&bgr;-D-木糖呋喃核苷被显示主要采用N-型呋喃糖环构象，通过构象分析和计算建模显示，存在于木糖-DNA中的2′-脱氧-&bgr;-D-木糖呋喃单体的呋喃环更倾向于S-型构象，从而最小化核碱基和3′-O-磷酸基团之间的立体排斥（Seela, F.; Wömer, Rosemeyer, H.Helv. Chem. Acta1994, 77, 883）。由于在RNA环境中对木糖构型的寡核苷酸的杂交性能和结合模式没有相关报告，因此旨在合成2′-O,4′-C-亚甲基-&bgr;-D-木糖呋喃核苷单体，并研究包含该单体的寡核苷酸的热稳定性。结果表明，完全修饰或几乎完全修饰的木糖-LNA对于高亲和力靶向互补核酸是有用的。考虑到C-3′的反向立体化学，这是一个令人惊讶的事实。很可能木糖-LNA单体在木糖-DNA单体序列环境中会具有增强亲和力的效果。
• Biocatalytic Deacylation Studies on Tetra-<i>O</i>-acyl-β-<scp>d</scp>-<i>xylo</i>furanosyl Nucleosides: Synthesis of <i>xylo</i>-LNA Monomers
  作者：Sunil K. Singh、Vivek K. Sharma、Kapil Bohra、Carl E. Olsen、Ashok K. Prasad

  DOI：10.1021/jo201060t

  日期：2011.9.16

  A Novozyme-435 catalytic methodology has been developed for selective deacylation of one of the acyloxy functions involving a primary -OH group over the other acyloxy functions involving primary and secondary -OH groups in 4'-C-acyloxymethyl-2',3',5'-tri-O-acyl-beta-D-xylofuranosyl nucleosides. Optimization of the biocatalytic reaction revealed that tetra-O-butanoyl-beta-D-xylofuranosyl nucleosides are the best substrates for the enzyme. The possibility of acyl migration during enzymatic deacylation reactions has been ruled out by carrying out biocatalytic deacylation reactions on mixed esters of 4'-C-hydroxymethyl-2',3',5'-tri-O-acetyl-beta-D-xylofuranosyl nucleosides. The developed methodology has been used for the efficient synthesis of xylo-LNA monomers T, U, A, and C in good yields.
• XYLO-LNA ANALOGUES
  申请人：Exiqon A/S

  公开号：EP1161439B1

  公开（公告）日：2010-04-21
• US7084125B2
  申请人：——

  公开号：US7084125B2

  公开（公告）日：2006-08-01