3,3-bis(hydroxymethyl)-5-methyl-(1H,3H,4H,7H)pyrimido[1,6-c][1,3]oxazine-6,8-dione | 139871-35-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3,3-bis(hydroxymethyl)-5-methyl-(1H,3H,4H,7H)pyrimido[1,6-c][1,3]oxazine-6,8-dione
• 英文别名: 3,3-Bis(hydroxymethyl)-5-methyl-1,4-dihydropyrimido[1,6-c][1,3]oxazine-6,8-dione
• CAS: 139871-35-5
• 化学式: C₁₀H₁₄N₂O₅
• 分子量: 242.232
• InChiKey: KEOYTEABZLMUAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,3-bis(hydroxymethyl)-5-methyl-(1H,3H,4H,7H)pyrimido[1,6-c][1,3]oxazine-6,8-dione 在 吡啶 、 四氮唑 、 ammonium hydroxide 、 乙醇 、 碘 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 24.0h， 生成 Phosphoric acid (2R,3S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-2-hydroxymethyl-tetrahydro-furan-3-yl ester (S)-3-hydroxymethyl-5-methyl-6,8-dioxo-4,6,7,8-tetrahydro-3H-pyrimido[1,6-c][1,3]oxazin-3-ylmethyl ester
  参考文献：
  名称：

  Synthesis and Enzymatic Stability of Acyclic Thymidine Dimer Analogues having a Constrained Anti-Glycosidic Conformation

  摘要：

  DOI：

  10.1080/07328319908044685
• 作为产物：
  描述：

  6-[2-[(1,3-bis-(tert-butyldiphenylsilyloxy)-2-methylthiomethyloxy)propyl]methyl]-2,4-dimethoxy-5-methylpyrimidine 在 sodium hydroxide 、 四丁基氟化铵 、 碘 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 66.0h， 生成 3,3-bis(hydroxymethyl)-5-methyl-(1H,3H,4H,7H)pyrimido[1,6-c][1,3]oxazine-6,8-dione
  参考文献：
  名称：

  抗构象约束无环核苷的改进合成制备

  摘要：

  通过将锂化的 2,4-二甲氧基-5,6-二甲基嘧啶与 1,3-双（叔丁基二苯基甲硅烷氧基）-丙烷-2-酮偶联，反构象限制性无环核苷的实际大规模合成已实现甲硫基甲基化、环化、水解和脱甲硅烷基化的顺序反应。

  DOI：

  10.1081/scc-100103324

文献信息

• Synthesis and Nuclease Stability of Dinucleotides Containing an<i>Anti</i>- conformationally Constrained Acyclic Thymidine
  作者：Ling-Yih Hsu、Kuo-Tsao Yang

  DOI：10.1080/07328319908044862

  日期：1999.9
• Synthesis of anti-restricted pyrimidine acyclic nucleosides
  作者：Ling Yih Hsu、Dean S. Wise、Louis S. Kucera、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jo00038a025

  日期：1992.6

  A number of pyrimidine acyclic nucleosides which are constrained in the anti conformation have been prepared via treatment of 5,6-dimethyl-2,4-dimethoxypyrimidine or 6-methyl-2,4-dimethoxypyrimidine with 1,3-bis-(benzyloxy)-2-propanone (3) to give 6-[[2-[1,3-bis(benzyloxy)-2-hydroxypropyl]]methyl]-2,4-dimethoxy-5-methylpyrimidine (5a) and 5b, respectively. Using acetic anhydride in DMSO, these compounds were converted to a 2-[[(methylthio)methyl]oxy] intermediate which was annulated to afford 2,2-bis[(benzyloxy)methyl]-8-methoxy-9-methyl-1H,2H,4H-pyrimido[1,6-c][1,3]oxazin-6-one (7a) and 7b, respectively, by using iodine in THF. Nucleophilic replacements at the 8-position and deblocking of 7a and 7b furnished the target compounds, 2,2-bis(hydroxymethyl)-9-methyl-(1H,4H,7H)-pyrimido[1,6-c][1,3]oxazine-6,8-dione (9a) and 9b, and the cytidine derivatives, 8-amino-2,2-bis(hydroxymethyl)-9-methyl-1H,4H-pyrimido[1,6-c][1,3]oxazin-6-one (12a) and 12b. Compounds 8b, 9a, 9b, 10b, 11b, 12a, and 12b were evaluated for activity against herpes viruses and human immunodeficiency virus (HIV). Compound 12a was slightly active against HIV at noncytotoxic concentrations. All other compounds were inactive at the highest concentration tested (100-mu-M).
• AN IMPROVED SYNTHETIC PREPARATION OF ANTI CONFORMATIONALLY CONSTRAINED ACYCLIC NUCLEOSIDES
  作者：Kuo-Tsao Yang、Ling-Yih Hsu

  DOI：10.1081/scc-100103324

  日期：2001.1

  Practical large-scale synthesis of anti conformationally constrained acyclic nucleosides has been attained from the coupling of lithiated 2,4-dimethoxy-5,6-dimethylpyrimidine with 1,3-bis(tert-butyldiphenylsilyloxy)-propan-2-one, followed by the sequential reactions of methylthiomethylation, ring cyclization, hydrolysis, and desilylation.

  通过将锂化的 2,4-二甲氧基-5,6-二甲基嘧啶与 1,3-双（叔丁基二苯基甲硅烷氧基）-丙烷-2-酮偶联，反构象限制性无环核苷的实际大规模合成已实现甲硫基甲基化、环化、水解和脱甲硅烷基化的顺序反应。
• Synthesis and Enzymatic Stability of Acyclic Thymidine Dimer Analogues having a Constrained Anti-Glycosidic Conformation
  作者：Ling-Yih Hsu、Kuo-Tsao Yang

  DOI：10.1080/07328319908044685

  日期：1999.6