1-[(2R,4S,5S)-4-azido-5-[[(2S)-8-methyl-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione | 1270965-89-3

• 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: 1-[(2R,4S,5S)-4-azido-5-[[(2S)-8-methyl-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• 英文别名: 1-[(2R,4S,5S)-4-azido-5-[[(2S)-8-methyl-2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-2-yl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1270965-89-3
• 化学式: C₁₈H₂₀N₅O₇P
• 分子量: 449.36
• InChiKey: NENSOAFAVKYDHT-KBVPZCQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-甲基水杨酸 在 lithium aluminium tetrahydride 、 N,N-双(苯基亚甲基)-1,2-乙二胺 、 copper(II) bis(trifluoromethanesulfonate) 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.5h， 生成 1-[(2R,4S,5S)-4-azido-5-[[(2S)-8-methyl-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  Diastereoselective Synthesis of cycloSaligenyl-Nucleosyl-Phosphotriesters

  摘要：

  AbstractA diastereoselective synthesis of cycloSal‐phosphotriesters (cycloSal=cycloSaligenyl) based on chiral auxiliaries has been developed that allows the synthesis of single diastereomers of the cycloSal‐pronucleotides. In previously described synthesis routes, the cycloSal‐compounds were always obtained as 1:1 diastereomeric mixtures that could be separated in only rare cases. However, it was shown that the diastereomers have different antiviral activity, toxicity, and hydrolysis stabilities. Here, first a chiral thiazoline derivative was used to prepare nonsubstituted and 5‐methyl‐cycloSal‐phosphotriesters in 48 and ≥95 % de (de=diastereomeric excess). However, this approach failed to give the important group of 3‐substituted cycloSal‐nucleotides. Therefore, two other chiral groups were discovered that allowed the synthesis of (RP)‐ and (SP)‐3‐methyl‐cycloSal‐phosphotriesters as well. The antiviral activity was found to be five‐ to 20‐fold different between the two individual diastereomers, which proved the importance of this approach.

  DOI：

  10.1002/chem.201002657

文献信息

• Diastereoselective Synthesis of cycloSaligenyl-Nucleosyl-Phosphotriesters
  作者：Edwuin H. Rios Morales、Jan Balzarini、Chris Meier

  DOI：10.1002/chem.201002657

  日期：2011.2.1

  AbstractA diastereoselective synthesis of cycloSal‐phosphotriesters (cycloSal=cycloSaligenyl) based on chiral auxiliaries has been developed that allows the synthesis of single diastereomers of the cycloSal‐pronucleotides. In previously described synthesis routes, the cycloSal‐compounds were always obtained as 1:1 diastereomeric mixtures that could be separated in only rare cases. However, it was shown that the diastereomers have different antiviral activity, toxicity, and hydrolysis stabilities. Here, first a chiral thiazoline derivative was used to prepare nonsubstituted and 5‐methyl‐cycloSal‐phosphotriesters in 48 and ≥95 % de (de=diastereomeric excess). However, this approach failed to give the important group of 3‐substituted cycloSal‐nucleotides. Therefore, two other chiral groups were discovered that allowed the synthesis of (RP)‐ and (SP)‐3‐methyl‐cycloSal‐phosphotriesters as well. The antiviral activity was found to be five‐ to 20‐fold different between the two individual diastereomers, which proved the importance of this approach.