(S)-1-(2,3-dihydroxypropyl)cytosine | 55559-70-1

• 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: (S)-1-(2,3-dihydroxypropyl)cytosine
• 英文别名: 1-(S)-(2,3-dihydroxypropyl)cytosine；4-amino-1-(2,3-dihydroxy-propyl)-1H-pyrimidin-2-one；(S)-N1-[(2,3-dihydroxy)propyl]cytosine；(S)-1-(2',3'-Dihydroxypropyl)-cytosin；Fpc5GG9hdk；4-amino-1-[(2S)-2,3-dihydroxypropyl]pyrimidin-2-one
• CAS: 55559-70-1
• 化学式: C₇H₁₁N₃O₃
• 分子量: 185.183
• InChiKey: LTTDCEYZEHQDGW-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  99.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-1-(2,3-dihydroxypropyl)cytosine 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 作用下， 以 吡啶 、 甲醇 、 氯仿 、 水 为溶剂， 反应 3.75h， 生成 环-1-(3-羟基-2-膦酰基甲氧基丙基)胞嘧啶
  参考文献：
  名称：

  Holy, Antonin; Rosenberg, Ivan; Dvorakova, Hana, Collection of Czechoslovak Chemical Communications, 1989, vol. 54, # 9, p. 2470 - 2501

  摘要：

  DOI：
• 作为产物：
  描述：

  1-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-4-methoxy-1H-pyrimidin-2-one 在 硫酸 、 氨 作用下， 以 水 为溶剂， 反应 8.0h， 生成 (S)-1-(2,3-dihydroxypropyl)cytosine
  参考文献：
  名称：

  Holy, Antonin; Rosenberg, Ivan; Dvorakova, Hana, Collection of Czechoslovak Chemical Communications, 1989, vol. 54, # 9, p. 2470 - 2501

  摘要：

  DOI：

文献信息

• Syntheses of Enantiomeric N-(3-Hydroxy-2-phosphonomethoxypropyl) Derivatives of Purine and Pyrimidine Bases
  作者：Antonín Holý

  DOI：10.1135/cccc19930649

  日期：——

  Methods of preparation of N-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) derivatives of (2S)- and (2R)-configuration (compounds I and XXVII, respectively) are described. The general method starts from the corresponding N-(2,3-dihydroxypropyl) derivatives which were converted either into the (R)-enantiomers XIII by reaction of the base with (R)-glycidol butyrate (XII) in the presence of cesium carbonate and subsequent methanolysis, or into the (S)-enantiomers XI by alkylation of the base with (R)-2,2-dimethyl-4-tosyloxymethyl-1,3-dioxolane (V) in the presence of the same reagent. The amino groups on the heterocyclic base in compounds XI and XIII were benzoylated by silylation followed by reaction with benzoyl chloride and the obtained N-benzoates XV and XVII on reaction with trityl chloride afforded the corresponding 3'-O-trityl derivatives XVI and XVIII. These compounds were condensed with bis(2-propyl) p-sulfonyloxymethylphosphonate (XXIII) in dimethylformamide in the presence of sodium hydride to give the fully protected diesters XXIV and XXVIII. These compounds could be selectively acid-hydrolyzed to remove the trityl group only under formation of compounds XXXV, or methanolyzed and then acid-hydrolyzed to remove the trityl and N-benzoyl groups and lead to compounds XXVI and XXX, or treated with bromotrimethylsilane to remove the trityl and 2-propyl group to give phosphonates of the type XXXI. All the three types of compounds were then converted into free phosphonates of the (S)-series (I) and the (R)-series (XXVII). Derivatives of cytosine (Ia, XXVIIa), adenine (Ib, XXVIIb), 2,6-diaminopurine (Ic, XXVIIc) and guanine (Id, XXVIId) were prepared. Condensation of the partially blocked adenine deriavtive XXXV with the tosyl derivative XXIII and subsequent deprotection afforded 9-(S)-(2,3-diphosphonomethoxy propyl)adenine (XLIII). Reaction of the same compound XXXV or its (R)-enantiomer XXXVIII with diethyl phosphonate , followed by deblocking, afforded 3'-O-phosphoryl derivatives (S)-HPMPA (XXXVII) and (R)-HPMPA (XL).

  描述了制备N-(3-羟基-2-膦甲氧基丙基)（HPMP）衍生物的方法，其中包括（2S）-和（2R）-构型的化合物I和XXVII。一般方法始于相应的N-(2,3-二羟基丙基)衍生物，通过将其转化为（R）-对映体XIII（通过碱与（R）-环氧丙酯（XII）在碳酸铯存在下的反应和随后的甲醇解）或通过在相同试剂存在下，通过碱与（R）-2,2-二甲基-4-对甲苯磺酰氧甲基-1,3-二氧兰（V）烷基化，将其转化为（S）-对映体XI。化合物XI和XIII中的杂环碱基上的氨基被硅烷化后与苯甲酰氯反应，得到的N-苯甲酸酯XV和XVII在与三苯甲基氯反应时生成相应的3'-O-三苯甲基衍生物XVI和XVIII。这些化合物与双(2-丙基)对磺酸氧甲基膦酸酯（XXIII）在二甲基甲酰胺中与氢化钠存在下反应，得到完全保护的二酯体XXIV和XXVIII。这些化合物可以选择性地酸水解以去除三苯甲基基团，仅形成化合物XXXV，或者经甲醇解然后酸水解以去除三苯甲基和N-苯甲酰基团，并导致化合物XXVI和XXX，或者经溴三甲基硅烷处理以去除三苯甲基和2-丙基基团，形成XXXI型膦酸酯。然后将这三种类型的化合物转化为（S）-系列（I）和（R）-系列（XXVII）的自由膦酸酯。制备了胞嘧啶（Ia、XXVIIa）、腺嘌呤（Ib、XXVIIb）、2,6-二氨基嘌呤（Ic、XXVIIc）和鸟嘌呤（Id、XXVIId）的衍生物。部分阻塞的腺嘌呤衍生物XXXV与甲磺酰衍生物XXIII进行缩合反应，随后去保护作用，得到9-(S)-(2,3-二磷酸甲氧基丙基)腺嘌呤（XLIII）。将相同化合物XXXV或其（R）-对映体XXXVIII与二乙基膦酸酯反应，随后去保护，得到3'-O-磷酰化衍生物（S）-HPMPA（XXXVII）和（R）-HPMPA（XL）。
• Synthesis of propane-2,3-diol combinatorial monomers
  作者：Oscar L. Acevedo、Robert S. Andrews

  DOI：10.1016/0040-4039(96)00745-9

  日期：1996.6

  es. A dimethoxytrityl-glycidol is reacted with alkyl or aryl Grignard reagents and then phosphitylated to yield 1-O-dimethoxytrityl-2-phosphoramidites. These compounds can be used for combinatorial oligomer synthesis.

  杂环碱与R-（+）-缩水甘油的碱催化反应得到杂芳基丙烷-2,3-二醇，其被官能化为3-O-二甲氧基三苯甲基-2-O-亚磷酰胺。使二甲氧基三苯甲基-缩水甘油与烷基或芳基格氏试剂反应，然后磷酸化以产生1-O-二甲氧基三苯甲基-2-亚磷酰胺。这些化合物可用于组合低聚物合成。
• Insight into the High Duplex Stability of the Simplified Nucleic Acid GNA
  作者：Mark K. Schlegel、Xiulan Xie、Lilu Zhang、Eric Meggers

  DOI：10.1002/anie.200803472

  日期：2009.1.19

  preorganized zipper: The entropic penalty for duplex formation is significantly smaller for the backbone‐simplified nucleic acid analogue GNA (glycol nucleic acid) than for DNA. This finding is consistent with a conformational preorganization of the single strands in combination with especially favorable stacking interactions in the corresponding GNA duplex (see picture).

  预先组织的拉链：骨架简化的核酸类似物GNA（乙二醇核酸）对双链体形成的熵损失明显小于DNA。这一发现与单链的构象预组织相结合，并与相应的GNA双链体中特别有利的堆积相互作用相结合（参见图片）。
• Process for the preparation of nucleotides
  申请人：Institute of Organic Chemistry and Biochemistry of the Academy of

  公开号：US05476938A1

  公开（公告）日：1995-12-19

  The present invention relates to a novel and economical process for the synthesis of HPMP-substituted nucleotide antiviral compounds. Also disclosed are novel intermediates produced in the process for the preparation of HPMPC.

  本发明涉及一种用于合成HPMP取代核苷酸抗病毒化合物的新颖且经济的方法。还揭示了在制备HPMPC过程中产生的新颖中间体。
• 9-(2-phosphonylmethoxyethyl) guanine
  申请人：Institute of Organic Chemistry and Biochemistry of the Academy of

  公开号：US05869467A1

  公开（公告）日：1999-02-09

  This invention relates to new nucleotide analogues and solves the technical problem of their use as biologically active compounds. The subject of this invention are N-(2-phosphonylmethoxyethyl) and N-(3-hydroxy-2-phosphonylmethoxypropyl) derivatives of pyrimidine and purine bases, easily accessible from heterocyolic bases and their N-(2-hydroxyethyl) or N-(2,3-dihydroxypropyl) derivatives. Some of the compounds, according to this invention, exhibit a marked antiviral activity or can be converted into such active compounds by chemical transformations.

  本发明涉及新的核苷酸类似物，并解决了它们作为生物活性化合物的使用的技术问题。本发明的主题是嘧啶和嘌呤碱基的N-（2-磷酸甲氧基乙基）和N-（3-羟基-2-磷酸甲氧基丙基）衍生物，这些衍生物容易从杂环碱基及其N-（2-羟乙基）或N-（2,3-二羟基丙基）衍生物中获得。根据本发明，其中一些化合物表现出显着的抗病毒活性或可以通过化学转化转化为这种活性化合物。