(Sp)-cycloSal-3'-O-acetylthymidine monophosphste | 1190113-51-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: (Sp)-cycloSal-3'-O-acetylthymidine monophosphste
• CAS: 1190113-51-9
• 化学式: C₁₉H₂₁N₂O₉P
• 分子量: 452.357
• InChiKey: TUXJVBVBHLQSST-CGRDTMOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  135.15
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  2-chloro-4H-benzo[d][1,3,2]dioxaphosphinine 2-oxide 在 N,N-双(苯基亚甲基)-1,2-乙二胺 、 copper(II) bis(trifluoromethanesulfonate) 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 199.5h， 生成 (Sp)-cycloSal-3'-O-acetylthymidine monophosphste
  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

• Linear Synthesis of Chiral cycloSal-Pronucleotides
  作者：Edwuin Hander Rios Morales、Cristina Arbelo Román、Jens Oliver Thomann、Chris Meier

  DOI：10.1002/ejoc.201100334

  日期：2011.8

  antivirally active nucleoside analogues. Until recently, the synthesis of these compounds always gave diastereoisomeric mixtures. Then, a convergent route for the stereospecific synthesis of cycloSal-triesters was described to give isomerically pure cycloSal-prodrugs for the treatment of viral diseases. Here, the development of a stereoselective synthesis of these pronucleotides using various chiral auxiliaries

  CycloSal-核苷-磷酸三酯是一类已知的具有抗病毒活性的核苷类似物的高效核苷酸前药（前核苷酸）。直到最近，这些化合物的合成总是得到非对映异构体混合物。然后，描述了一种立体有择合成环三酯的收敛途径，以提供用于治疗病毒性疾病的异构纯环萨尔前药。在这里，描述了使用各种手性助剂对这些核苷酸前体进行立体选择性合成的发展。与吡咯烷-或吡咯烷酮衍生物相比，发现衍生自缬氨醇的噻唑烷满足充当合适手性部分的所有三个要求，允许：(i) 强手性转移，(ii) 形成可分离的非对映异构中间体，(iii) 合适的离去基团，允许在温和的反应条件下在最后一步中引入核苷类似物（例如，d4T）。以超过 95% 的非常高的非对映异构体过量获得标题化合物。
• METHOD FOR THE STEREOSELECTIVE SYNTHESIS OF PHOSPHORUS COMPOUNDS
  申请人：Meier Chris

  公开号：US20110028705A1

  公开（公告）日：2011-02-03

  The present invention relates to a method for stereoselective synthesis of phosphorus compounds, whereby in the first reaction step a chiral auxiliary on the phosphorus atom of phosphoryl chloride, thiophosphoryl chloride or phosphorus trichloride is covalently bonded, the product from the first reaction step is reacted in the following step with an alcohol, thiol, or amine as the nucleophile in the presence of a base, and in the last step the chiral auxiliary is displaced from the product of the following step by a nucleophile.

  本发明涉及一种手性选择性合成磷化合物的方法，其中在第一反应步骤中，将手性辅助基共价键结到磷酰氯化物、硫代磷酰氯或三氯化磷的磷原子上，第一反应步骤的产物在下一步中与醇、硫醇或胺作为亲核试剂在碱存在下反应，最后一步中通过亲核试剂从下一步反应产物中取代手性辅助基。