1-β-D-arabinofuranosyl-1H-pyrimidin-4-one | 65025-03-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-β-D-arabinofuranosyl-1H-pyrimidin-4-one
• 英文别名: 1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• CAS: 65025-03-8
• 化学式: C₉H₁₂N₂O₅
• 分子量: 228.205
• InChiKey: RPQZTTQVRYEKCR-OOJXKGFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-β-D-arabinofuranosyl-1H-pyrimidin-4-one 在 sodium hydroxide 作用下， 反应 4.0h， 生成 1-Amino-(1,2-carbamoyl)-β-D-arabinofuranose
  参考文献：
  名称：

  The decomposition of 1-(.beta.-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) in alkali: mechanism and products

  摘要：

  The mechanism of the base-catalyzed degradation of 1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine, 1a) and closely related analogues was studied by NMR spectroscopy and GC-MS. Addition of sodium deuteroxide to a solution of 1a in D2O effected a rapid and irreversible reaction characterized by complete degradation of the heterocyclic pyrimidinone ring. H-1 NMR data suggested that 1a was initially converted to the labile aldehyde 10. This was later confirmed by similar degradation of the 5-fluoro analogue 1b to the more stable aldehyde 9. The alkaline degradation of 1a reaches an end point after 4 h at room temperature with one identifiable product being the anomerized alpha-N1-O2 cyclic carbamate 6. Compound 6 was formed by degradation of both 1a and 1b. The ara epimer 1c formed the beta-carbamate 8, and the 5'-O-methyl derivative 1d proceeded to the 5-O-methyl carbamate 7. An inventory of the remaining atoms yields a formula which suggested the complementary component of the degradation to be an immediate precursor to 1,3-propane dialdehyde (malondialdehyde, MDA). Support for this proposal was evident in both the H-1 and C-13 NMR spectra of the basic reaction mixture which showed resonances that corresponded closely with those published for authentic MDA at pH 9.6. The presence of MDA was unequivocally proven by derivatization of the acidified degradation mixture with hydrazinobenzothiazole (HBT) to give the known adduct 11. GC-MS analysis of the adduct obtained from HBT and the MDA formed during the decomposition reaction was identical to the adduct prepared from authentic MDA and HBT. Since the 5'-O-methyl derivative 1d yielded the same type of products as those analogues with the 5'-hydroxyl free, it was concluded that the 5'-OH was not essential for alkaline lability. This contradicts the original literature assumption that some type of cyclization of the carbohydrate with the pyrimidinone system may be a first step in the mechanism. The data herein suggest that the base-catalyzed decomposition begins with the preferential attack at the 6-position of 2-pyrimidinone nucleosides. The discovery that a known mutagen (MDA) is a product in the degradation of 1a suggests that a relationship could exist between the chemical susceptibility of 1a and its unique biological activity.

  DOI：

  10.1021/jo00028a026

文献信息

• US5641758A
  申请人：——

  公开号：US5641758A

  公开（公告）日：1997-06-24
• The decomposition of 1-(.beta.-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) in alkali: mechanism and products
  作者：Joseph J. Barchi、Steven Musser、Victor E. Marquez

  DOI：10.1021/jo00028a026

  日期：1992.1

  The mechanism of the base-catalyzed degradation of 1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine, 1a) and closely related analogues was studied by NMR spectroscopy and GC-MS. Addition of sodium deuteroxide to a solution of 1a in D2O effected a rapid and irreversible reaction characterized by complete degradation of the heterocyclic pyrimidinone ring. H-1 NMR data suggested that 1a was initially converted to the labile aldehyde 10. This was later confirmed by similar degradation of the 5-fluoro analogue 1b to the more stable aldehyde 9. The alkaline degradation of 1a reaches an end point after 4 h at room temperature with one identifiable product being the anomerized alpha-N1-O2 cyclic carbamate 6. Compound 6 was formed by degradation of both 1a and 1b. The ara epimer 1c formed the beta-carbamate 8, and the 5'-O-methyl derivative 1d proceeded to the 5-O-methyl carbamate 7. An inventory of the remaining atoms yields a formula which suggested the complementary component of the degradation to be an immediate precursor to 1,3-propane dialdehyde (malondialdehyde, MDA). Support for this proposal was evident in both the H-1 and C-13 NMR spectra of the basic reaction mixture which showed resonances that corresponded closely with those published for authentic MDA at pH 9.6. The presence of MDA was unequivocally proven by derivatization of the acidified degradation mixture with hydrazinobenzothiazole (HBT) to give the known adduct 11. GC-MS analysis of the adduct obtained from HBT and the MDA formed during the decomposition reaction was identical to the adduct prepared from authentic MDA and HBT. Since the 5'-O-methyl derivative 1d yielded the same type of products as those analogues with the 5'-hydroxyl free, it was concluded that the 5'-OH was not essential for alkaline lability. This contradicts the original literature assumption that some type of cyclization of the carbohydrate with the pyrimidinone system may be a first step in the mechanism. The data herein suggest that the base-catalyzed decomposition begins with the preferential attack at the 6-position of 2-pyrimidinone nucleosides. The discovery that a known mutagen (MDA) is a product in the degradation of 1a suggests that a relationship could exist between the chemical susceptibility of 1a and its unique biological activity.