5-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]oxolan-2-yl]-5-methylimidazolidine-2,4-dione | 153363-17-8

• 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: 5-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]oxolan-2-yl]-5-methylimidazolidine-2,4-dione
• CAS: 153363-17-8
• 化学式: C₂₉H₃₀N₂O₇
• 分子量: 518.566
• InChiKey: OOQFHXKDNDUBLM-DPUCTUKRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.74
• 重原子数：
  38.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  117.56
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  5-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]oxolan-2-yl]-5-methylimidazolidine-2,4-dione 在 ammonium hydroxide 、 溶剂黄146 作用下， 反应 4.5h， 生成 1-(2-deoxy-β-D-erythro-pentofuranosyl)-5(R)-hydroxy-5-methylhydantoin
  参考文献：
  名称：

  Repair and Coding Properties of 5-Hydroxy-5-methylhydantoin Nucleosides Inserted into DNA Oligomers

  摘要：

  1-(2-Deoxy-beta-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin (5-OH-5-Me-dHyd) (3) has been shown to be a major oxidation product of thymidine formed upon exposure of DNA to (OH)-O-.-radical and excited photosensitizers. To investigate the biological and structural significance of the 6-OH-5-Me-dHyd residue to DNA, the latter modified 2'-deoxyribonucleoside was chemically prepared and then site-specifically incorporated into oligo deoxyribonucleotides. This was efficiently achieved using the phosphoramidite approach that involved mild deprotection conditions. The purity and the integrity of the modified synthetic DNA fragments were checked using different complementary techniques such as HPLC and polyacrylamide gel electrophoresis, together with electrospray ionization and MALDI-TOF mass spectrometry. The piperidine test applied to 5-OH-5-Me-dHyd containing oligonucleotides showed a weak instability of hydantoin nucleoside inserted into the oligonucleotide chain. Several enzymatic experiments aimed at determining the biochemical features of such a DNA lesion were carried out. Thus, processing of 5-OH-5-Me-dHyd by nuclease P-1, snake venom phosphodiesterase, and calf spleen phosphodiesterase was investigated. The specificity and the mechanism of excision of the lesion by several bacterial and yeast DNA N-glycosylases, namely, endonuclease III (endo III), endonuclease VIII (endo VIII), formamidopyrimidine DNA N-glycosylase (Fpg), Ntg1 protein (Ntg1), Ntg2 protein (Ntg2), and Ogg1 protein (yOgg1), were also determined. These repair studies clearly showed that all these enzymes, with the exception of the yOgg1 protein, are able to recognize and remove 5-hydroxy-5-methylhydantoin from the double-stranded DNA fragment. Finally, a 22-mer DNA oligomer bearing a 5-OH-5-Me-dHyd residue was used as a template to study the in vitro nucleotide incorporation opposite the damage by the Klenow fragment of Escherichia coli polymerase I, Taq DNA polymerase, and DNA polymerase beta. Thus, it may be concluded that the oxidized thymine residue is a strongly blocking lesion for the three studied DNA polymerases.

  DOI：

  10.1021/tx000005+
• 作为产物：
  描述：

  5'-O-(4-monomethoxytrityl)-2'-deoxythymidine 在 lead(IV) acetate 、 potassium permanganate 、 camphor-10-sulfonic acid 作用下， 以 吡啶 为溶剂， 反应 4.0h， 以41%的产率得到5-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]oxolan-2-yl]-5-methylimidazolidine-2,4-dione
  参考文献：
  名称：

  The synthesis of 5-hydroxy-5-methylhydantoin nucleoside and its insertion into oligodeoxyribonucleotides

  摘要：

  5-hydroxy-5-methylbydantoin is a nucleobase lesion induced by the action of ionizing radiation on thymine residue in DNA. The protected nucleoside cyanoethyldiisopropylphosphoramidite has been synthesized and used to prepare chemical DNA fragments containing 5-hydroxy-5-methylhydantoin moieties.

  DOI：

  10.1016/s0040-4039(00)61462-4