5-氟嘧啶-2-酮 beta-呋喃核糖苷 | 64967-16-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 5-氟嘧啶-2-酮 beta-呋喃核糖苷
• 中文别名: 5-氟嘧啶-2-酮beta-呋喃核糖苷
• 英文名称: 1-β-D-ribofuranosyl-5-fluoropyrimidin-2(1H)-one
• 英文别名: 5-Fluorozebularine；5-fluoro-1-β-D-ribofuranosyl-1H-pyrimidin-2-one；1-(β-D-Ribofuranosyl)-5-fluor-2-pyrimidinon；1beta-D-Ribofuranosyl-5-fluoropyrimidin-2(1H)-one；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-fluoropyrimidin-2-one
• CAS: 64967-16-4
• 化学式: C₉H₁₁FN₂O₅
• 分子量: 246.195
• InChiKey: BISROEGZKWHITE-WCTZXXKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  17
• 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：
  6

反应信息

• 作为反应物：
  描述：

  5-氟嘧啶-2-酮 beta-呋喃核糖苷 在 sodium hydroxide 作用下， 反应 0.03h， 生成 1--β-D-ribofuranose
  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
• 作为产物：
  描述：

  1-乙酰氧基-2,3,5-三苯甲酰氧基-1-beta-D-呋喃核糖 在 氨 、 四氯化锡 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 5-氟嘧啶-2-酮 beta-呋喃核糖苷
  参考文献：
  名称：

  2（1H）-嘧啶酮核糖苷（zebularine）及其氟化类似物的抗肿瘤特性。

  摘要：

  已合成2（1H）-嘧啶酮核糖苷（zebularine，1b）及其5-氟（6b）和2'-ara-氟（7b）类似物，并在体内作为抗肿瘤药进行了评估。Zebularine可延长ca的寿命（ILS）值。70％抵抗腹膜内（ip）鼠B16黑色素瘤，50％抵抗P388白血病。腹膜内或口服给药时，该化合物对经腹膜内或皮下植入的L1210白血病具有活性，在400 mg / kg的最佳剂量下产生的ILS值约为100％。1b对抗ara C的L1210也有活性（60％ILS）。类似的未取代的嘌呤核糖苷核苷（2）对P388白血病（60％ILS）的活性中等。尽管高剂量的2'-ara-fluorozebularine（7b）对L1210白血病的活性很小（40％ILS），但5-氟类似物6b的活性比zebularine高，并且大约为5。强效100倍。尽管6b的活性与1b的抗P388白血病的活性大致相同，但在该模型中也实现了

  DOI：

  10.1021/jm00115a017