((2R,5S)-5-(4-acetamido-2-oxopyrimidin-1(2H)-yl)-1,3-oxathiolan-2-yl)methyl benzoate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: ((2R,5S)-5-(4-acetamido-2-oxopyrimidin-1(2H)-yl)-1,3-oxathiolan-2-yl)methyl benzoate
• 英文别名: (2R,5S)-5-(4'-acetamido-2'-oxo-pyrimidin-1'-yl)-1,3-oxathiolane-2-methyl benzoate；[(2R,5S)-5-(4-acetamido-2-oxopyrimidin-1-yl)-1,3-oxathiolan-2-yl]methyl benzoate
• 化学式: C₁₇H₁₇N₃O₅S
• 分子量: 375.405
• InChiKey: MKSGJSLVQHXINJ-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ((2R,5S)-5-(4-acetamido-2-oxopyrimidin-1(2H)-yl)-1,3-oxathiolan-2-yl)methyl benzoate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 14.0h， 以89%的产率得到拉米夫定
  参考文献：
  名称：

  通过酶动力学动力学拆分有效的不对称合成拉米夫定。

  摘要：

  通过新型表面活性剂处理的枯草杆菌蛋白酶嘉士伯催化的动态动力学拆分方案，仅在三个步骤中不对称合成了抗HIV核苷拉米夫定。拉米夫定的对映体也可以使用由南极假丝酵母脂肪酶B催化的相同方案获得。

  DOI：

  10.1039/c3cc45551c
• 作为产物：
  描述：

  N4-乙酰胞嘧啶 在 碘代三甲硅烷 作用下， 以 乙腈 为溶剂， 反应 4.25h， 生成 ((2R,5S)-5-(4-acetamido-2-oxopyrimidin-1(2H)-yl)-1,3-oxathiolan-2-yl)methyl benzoate
  参考文献：
  名称：

  通过酶动力学动力学拆分有效的不对称合成拉米夫定。

  摘要：

  通过新型表面活性剂处理的枯草杆菌蛋白酶嘉士伯催化的动态动力学拆分方案，仅在三个步骤中不对称合成了抗HIV核苷拉米夫定。拉米夫定的对映体也可以使用由南极假丝酵母脂肪酶B催化的相同方案获得。

  DOI：

  10.1039/c3cc45551c

文献信息

• 2-Substituted-4-substituted-1,3-dioxolanes and use thereof
  申请人：Biochem Pharma Inc.

  公开号：US06350753B1

  公开（公告）日：2002-02-26

  Nucleoside analogues containing a 1,3-dioxolane structure are suitable antiviral agents, particulary for the treatment of the HIV infections in mammals, especially humans. Examples of the nucleoside analogues include: cis-2-acetoxymethyl-4-(thymin-1′-yl)-1,3,-dioxolane, cis-2-hydroxymethyl-4-(thymin-1′-yl)-1,3-dioxolane, cis-2-benzoyloxymethyl-4-(cytosin-1′-yl)-1,3-dioxolane, and cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-dioxolane. These compounds can be in the form of their racemates or their separate enantiomers.

  含有1,3-二氧杂环戊烷结构的核苷类似物是适用的抗病毒药物，特别适用于治疗哺乳动物，尤其是人类的HIV感染。核苷类似物的例子包括：顺式-2-乙酰氧甲基-4-(胸腺嘧啶-1'-基)-1,3-二氧杂环戊烷，顺式-2-羟甲基-4-(胸腺嘧啶-1'-基)-1,3-二氧杂环戊烷，顺式-2-苯甲酰氧甲基-4-(胞嘧啶-1'-基)-1,3-二氧杂环戊烷，以及顺式-2-羟甲基-4-(胞嘧啶-1'-基)-1,3-二氧杂环戊烷。这些化合物可以是它们的外消旋体或它们的单独对映体形式。
• Enantioselective enzymatic synthesis of the anti-viral agent lamivudine (3TC™)
  作者：John Milton、Stephen Brand、Martin F. Jones、Christopher M. Rayner

  DOI：10.1016/0040-4039(95)01380-z

  日期：1995.9

  A novel enzymatic resolution of alpha-acetoxysulfides has been used as the key step in the synthesis of the important antiviral nucleoside analogue lamivudine. The synthesis proceeds via a configurationally stable hemithioacetal which cyclises in situ to form the required oxathiolane nucleus, which can then be converted into the target nucleoside in 4 steps.
• Synthesis and Biological Evaluation of a New N⁴-(N-Formyl Peptide)- 2′,3′-Dideoxy-3′-Thiacytidine as Anti-Hiv Prodrug
  作者：Michel Camplo、Philippe Faury、Anne-Sophie Charvet、Florence Lederer、Jean-Claude Chermann、Jean-Louis Kraus

  DOI：10.1080/07328319308019017

  日期：1993.7

  The synthesis of a new analogue of 2,3'-dideoxy-3'-thiacytidine 9 covalently linked to an N-formyl methionyl leucyl phenylalanine peptide is described. This new prodrug analogue has been tested on the one hand as activator of human polymorphonuclear leukocytes (an EC50 value of 1.8 10(-5) M was determined from dose-response curve for superoxide production) and on the other hand as inhibitor Of the syncitium formation caused by HIV-1 in MT4-cells (IC50 = 8.0 +/- 0.8 muM). In so far as this new prodrug possesses these two biological properties, it represents a useful ''chemical-head' capable of targeting specific receptors located on leukocytes membranes.
• A PROCESS FOR STEREOSELECTIVE SYNTHESIS OF LAMIVUDINE
  申请人：Shanghai Desano Pharmaceutical Holding Co., Ltd.

  公开号：EP2161267B1

  公开（公告）日：2014-04-30
• Efficient asymmetric synthesis of lamivudine <i>via</i> enzymatic dynamic kinetic resolution
  作者：Lei Hu、Fredrik Schaufelberger、Yan Zhang、Olof Ramström

  DOI：10.1039/c3cc45551c

  日期：——

  lamivudine was asymmetrically synthesized in only three steps via a novel surfactant-treated subtilisin Carlsberg-catalyzed dynamic kinetic resolution protocol. The enantiomer of lamivudine could also be accessed using the same protocol catalyzed by Candida antarctica lipase B.

  通过新型表面活性剂处理的枯草杆菌蛋白酶嘉士伯催化的动态动力学拆分方案，仅在三个步骤中不对称合成了抗HIV核苷拉米夫定。拉米夫定的对映体也可以使用由南极假丝酵母脂肪酶B催化的相同方案获得。