1,2,3,4-tetrahydro-1-(2',3'-O-isopropylidenethymidyl)-quinoline | 149204-06-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1,2,3,4-tetrahydro-1-(2',3'-O-isopropylidenethymidyl)-quinoline
• 英文别名: 1,2,3,4-tetrahydro-1-(2',3'-O-isopropylidenethymidyl)quinoline；1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-5-(3,4-dihydro-2H-quinolin-1-ylmethyl)pyrimidine-2,4-dione
• CAS: 149204-06-8
• 化学式: C₂₂H₂₇N₃O₆
• 分子量: 429.473
• InChiKey: RWSXFXGTPHMECY-SOAMZJECSA-N

物化性质

• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,2,3,4-tetrahydro-1-(2',3'-O-isopropylidenethymidyl)-quinoline 在 palladium on activated charcoal 盐酸 、 氢氧化钾 、 氢气 作用下， 以 丙酮 为溶剂， 25.0~200.0 ℃ 、344.73 kPa 条件下， 反应 7.0h， 生成 2',3'-O,O-isopropylidene-5-methyluridine
  参考文献：
  名称：

  Insight into the Chemical Mechanism of Thymidylate Synthase-Catalyzed Reaction Through the Evaluation of Chemical Models: The Role of C6 Sulfhydryl Addition During the Reductive Elimination Step of the Reaction1

  摘要：

  Thymidylate synthase catalyzes the last step of the de novo synthesis of thymidine-5'-monophosphate (TMP), which has long been a target for the development of effective anticancer agents. Model compounds (15, 16, 17) were used to study the effect of C6 nucleophilic addition on the reductive elimination step of the TS-catalyzed reaction. Results suggest that C6 addition facilitates the reductive elimination of the H(2)folate moiety of the ternary intermediate (3). Therefore, the reaction pathway (pathway (b)) with the participation of C6 sulfhydryl addition during the reductive elimination process is the energetically favored process. Consequently, the elimination of the cysteine sulfhydryl group from the C6 position is the last step of the reaction before the dissociation of the products from the enzyme. (C) 1994 Academic Press, Inc.

  DOI：

  10.1006/bioo.1994.1034
• 作为产物：
  描述：

  1,2,3,4-四氢喹啉 、 5-formyl-2',3'-O-isopropylideneuridine 在 sodium cyanoborohydride 、 zinc(II) chloride 作用下， 以 甲醇 为溶剂， 反应 36.0h， 以84%的产率得到1,2,3,4-tetrahydro-1-(2',3'-O-isopropylidenethymidyl)-quinoline
  参考文献：
  名称：

  A chemical model for the fragmentation reaction in thymidylate synthase catalysis. Synthesis and evaluation of a 5-methylene-1-(1,2,3,4-tetrahydroquinolyl)-6-allyluridine

  摘要：

  Compounds 5 and 6 were synthesized as models to investigate the reactivity of proposed intermediate 2 in thymidylate synthase (TS) catalysis as it fragments to form dTMP. The mechanism of the fragmentation (homolytic or heterolytic) of model 6 was determined via subsequent interaction of the fragmented center with the C6 allyl substituent. The results were consistent with an ionic fragmentation of 6, followed by loss of an allylic proton, and subsequent thermal electrocyclic or Diels-Alder reactions of the resulting trienes 13 and 14, respectively. Independent generation of radicals analogous to that produced from a radical fragmentation of model 6 did not result in formation of trienes 13 and 14.

  DOI：

  10.1021/jo00062a014

文献信息

• A chemical model for the fragmentation reaction in thymidylate synthase catalysis. Synthesis and evaluation of a 5-methylene-1-(1,2,3,4-tetrahydroquinolyl)-6-allyluridine
  作者：John R. Kagel、Binghe Wang、Mathias P. Mertes

  DOI：10.1021/jo00062a014

  日期：1993.5

  Compounds 5 and 6 were synthesized as models to investigate the reactivity of proposed intermediate 2 in thymidylate synthase (TS) catalysis as it fragments to form dTMP. The mechanism of the fragmentation (homolytic or heterolytic) of model 6 was determined via subsequent interaction of the fragmented center with the C6 allyl substituent. The results were consistent with an ionic fragmentation of 6, followed by loss of an allylic proton, and subsequent thermal electrocyclic or Diels-Alder reactions of the resulting trienes 13 and 14, respectively. Independent generation of radicals analogous to that produced from a radical fragmentation of model 6 did not result in formation of trienes 13 and 14.
• Insight into the Chemical Mechanism of Thymidylate Synthase-Catalyzed Reaction Through the Evaluation of Chemical Models: The Role of C6 Sulfhydryl Addition During the Reductive Elimination Step of the Reaction1
  作者：B.H. Wang、J.R. Kagel、M.P. Mertes、K. Bowmanjames

  DOI：10.1006/bioo.1994.1034

  日期：1994.12

  Thymidylate synthase catalyzes the last step of the de novo synthesis of thymidine-5'-monophosphate (TMP), which has long been a target for the development of effective anticancer agents. Model compounds (15, 16, 17) were used to study the effect of C6 nucleophilic addition on the reductive elimination step of the TS-catalyzed reaction. Results suggest that C6 addition facilitates the reductive elimination of the H(2)folate moiety of the ternary intermediate (3). Therefore, the reaction pathway (pathway (b)) with the participation of C6 sulfhydryl addition during the reductive elimination process is the energetically favored process. Consequently, the elimination of the cysteine sulfhydryl group from the C6 position is the last step of the reaction before the dissociation of the products from the enzyme. (C) 1994 Academic Press, Inc.