cis-1-[2-(hydroxymethyl)-1,3-dioxan-5-yl]-5-methylpyrimidine-2,4(1H,3H)-dione | 191802-78-5

• 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: cis-1-[2-(hydroxymethyl)-1,3-dioxan-5-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
• CAS: 191802-78-5
• 化学式: C₁₀H₁₄N₂O₅
• 分子量: 242.232
• InChiKey: VZOFSMQVTSJKRB-OCAPTIKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.25
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.55
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  cis-1-[2-(hydroxymethyl)-1,3-dioxan-5-yl]-5-methylpyrimidine-2,4(1H,3H)-dione 在 三氟化硼乙醚 作用下， 以 氘代二甲亚砜 为溶剂， 生成 trans-1-[2-(hydroxymethyl)-1,3-dioxan-5-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Ring-Expanded Nucleoside Analogues. 1,3-Dioxan-5-yl Pyrimidines

  摘要：

  1,3-Dioxan-5-yl pyrimidine nucleoside analogues, higher homologues of antiviral and anticancer 1,3-dioxolanes, were prepared from bis-1,3-tritylglycerol and 3-benzoylated bases (uracil, 5-fluorouracil, thymine). Mitsunobu condensation, deprotection, and cycloacetalization gave cis/trans mixtures of 2,5-disubstituted-1,3-dioxanes in which the desired cis stereoisomers predominated. Cytosine derivatives could not be obtained in this manner; N-4-benzoylcytosine afforded an O-2 alkylated Mitsunobu product that rearranged to an O-2-(2,3-dihydroxypropyl)cytosine on detritylation with aqueous acetic acid. Cytosine and 5-fluorocytosine nucleosides were therefore prepared from the corresponding uracils via their 1,2,4-triazole derivatives. H-1 NMR data established the conformational preference for equatorial 2'-hydroxymethyl and axial 5'-base in the cis isomers; the trans compounds were diequatorial. Despite their conformations, the cis nucleosides showed no antiviral activity.

  DOI：

  10.1021/jo9715231
• 作为产物：
  描述：

  N-3-benzoylthymine 在 氨 、 对甲苯磺酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 80.0 ℃ 、266.64 Pa 条件下， 反应 26.5h， 生成 cis-1-[2-(hydroxymethyl)-1,3-dioxan-5-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Ring-Expanded Nucleoside Analogues. 1,3-Dioxan-5-yl Pyrimidines

  摘要：

  1,3-Dioxan-5-yl pyrimidine nucleoside analogues, higher homologues of antiviral and anticancer 1,3-dioxolanes, were prepared from bis-1,3-tritylglycerol and 3-benzoylated bases (uracil, 5-fluorouracil, thymine). Mitsunobu condensation, deprotection, and cycloacetalization gave cis/trans mixtures of 2,5-disubstituted-1,3-dioxanes in which the desired cis stereoisomers predominated. Cytosine derivatives could not be obtained in this manner; N-4-benzoylcytosine afforded an O-2 alkylated Mitsunobu product that rearranged to an O-2-(2,3-dihydroxypropyl)cytosine on detritylation with aqueous acetic acid. Cytosine and 5-fluorocytosine nucleosides were therefore prepared from the corresponding uracils via their 1,2,4-triazole derivatives. H-1 NMR data established the conformational preference for equatorial 2'-hydroxymethyl and axial 5'-base in the cis isomers; the trans compounds were diequatorial. Despite their conformations, the cis nucleosides showed no antiviral activity.

  DOI：

  10.1021/jo9715231

文献信息

• Synthesis of Six-Membered Nucleoside Analogs. Part 1: Pyrimidine Nucleosides Based on the 1,3-Dioxane Ring System
  作者：Daniel C. Capaldi、Alessandra Eleuteri、Qin Chen、Raymond F. Schinazi

  DOI：10.1080/07328319708001358

  日期：1997.4

  The synthesis of pyrimidine nucleosides, cis-N-1-[(2-hydroxymethyl)-1,3-dioxan-5-yl]uracil (4) cis-N-1-[(2-hydroxymethyl)-1,3-dioxan-5-yl]thymine (5) and cis-N-1-[(2-hydroxymethyl)-1,3-dioxan-5-yl]cytosine (6) and their corresponding trans isomers is described. Compound 4 showed modest, selective activity against human immunodeficiency virus in acutely infected primary human lymphocytes.
• A New and Versatile Synthesis of 1,3-Dioxan-5-yl-pyrimidine and Purine Nucleoside Analogues
  作者：Livio Brasili、Claudia Sorbi、Adolfo Prandi、Umberto Battisti、Silvia Franchini、Andrea Cornia、Jan Balzarini、Lak Jeong、Sang Lee、Jayoung Song

  DOI：10.1055/s-0034-1380112

  日期：——

  1,3-Dioxan-5-yl pyrimidine and purine nucleoside analogues were prepared following a new and versatile synthetic strategy. These analogues were synthesized via nucleophilic addition of the selected nucleobase to a 1,3-dioxane scaffold that presents an appropriate leaving group in position 5. In particular cis and trans isomers of purine/pyrimidine nucleosides and their halogenated homologues were obtained. NMR experiments, carried out on the cis isomers, led to assignment of an equatorial orientation to the 2-hydroxymethyl group and axial orientation to the nucleobase in position 5 of the 1,3-dioxane. The trans isomers showed a diequatorial orientation of these groups. These assignments were confirmed by X-ray crystallographic studies.