methyl (3R,4S,5R)-3-azido-4,5-dihydroxy-cyclohex-1-en-1-carboxylate | 179927-12-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (3R,4S,5R)-3-azido-4,5-dihydroxy-cyclohex-1-en-1-carboxylate
• 英文别名: methyl (3R,4R,5R)-3-azido-4,5-dihydroxycyclohexene-1-carboxylate
• CAS: 179927-12-9
• 化学式: C₈H₁₁N₃O₄
• 分子量: 213.193
• InChiKey: CBLCRGITIHNWRN-FSDSQADBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (3R,4S,5R)-3-azido-4,5-dihydroxy-cyclohex-1-en-1-carboxylate 在 sodium hydroxide 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3(R)-aminoshikimic acid
  参考文献：
  名称：

  Synthesis of (−)-3(R)-amino-4(R),5(R)-dihydroxy-1-cyclohexene-1-carboxylic acid: The 3(R)-amino analogue of (−)-shikimic acid

  摘要：

  (-)-3(R)-氨基-4(R),5(R)-二羟基-1-环己烯-1-羧酸（即 (-)-地衣壳素酸的 3(R)-氨基类似物）已从 (-)-地衣壳素酸在七步反应中成功合成。

  DOI：

  10.1016/0960-894x(96)00011-x
• 作为产物：
  描述：

  莽草酸 在 迭氮酸 、 偶氮二甲酸二异丙酯 、 硫酸 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 、 对硝基苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 48.0h， 生成 methyl (3R,4S,5R)-3-azido-4,5-dihydroxy-cyclohex-1-en-1-carboxylate
  参考文献：
  名称：

  Mycobacterium tuberculosis Shikimate Kinase Inhibitors: Design and Simulation Studies of the Catalytic Turnover

  摘要：

  Shikimate kinase (SK) is an essential enzyme in several pathogenic bacteria and does not have any counterpart in human cells, thus making it an attractive target for the development of new antibiotics. The key interactions of the substrate and product binding and the enzyme movements that are essential for catalytic turnover of the Mycobacterium tuberculosis shikimate kinase enzyme (Mt-SK) have been investigated by structural and computational studies. Based on these studies several substrate analogs were designed and assayed. The crystal structure of Mt-SK in complex with ADP and one of the most potent inhibitors has been solved at 2.15 angstrom. These studies reveal that the fixation of the diaxial conformation of the C4 and C5 hydroxyl groups recognized by the enzyme or the replacement of the C3 hydroxyl group in the natural substrate by an amino group is a promising strategy for inhibition because it causes a dramatic reduction of the flexibility of the LID and shikimic acid binding domains. Molecular dynamics simulation studies showed that the product is expelled from the active site by three arginines (Arg117, Arg136, and Arg58). This finding represents a previously unknown key role of these conserved residues. These studies highlight the key role of the shikimic acid binding domain in the catalysis and provide guidance for future inhibitor designs.

  DOI：

  10.1021/ja405853p

文献信息

• An efficient transformation of quinic acid to shikimic acid derivatives
  作者：Cristina Alves、M.Teresa Barros、Christopher D. Maycock、M.Rita Ventura

  DOI：10.1016/s0040-4020(99)00431-7

  日期：1999.7

  The synthesis of (−)-methyl shikimate and (−)-methyl 3-epi-shikimate and the 3-aminoshikimate derivative have been achieved via short and efficient routes from quinic acid.

  （-）- sh草酸甲酯和（-）-3-表-shi草酸酯和3-氨基shi草酸酯衍生物的合成已经通过短而有效的途径由奎宁酸实现。
• The shikimate pathway. Part 8. Synthesis of (−)-3(R)-amino-4(R),5(R)-dihydroxy-1-cyclohexene-1-carboxylic acid: The 3(R)-amino analogue of (−)-shikimic acid
  作者：Harry Adams、Neil A. Bailey、Roger Brettle、Richard Cross、Martyn Frederickson、Edwin Haslam、Fiona S. MacBeath、Gareth M. Davies

  DOI：10.1016/0040-4020(96)00398-5

  日期：1996.6

  The first successful method for the introduction of nitrogenous functionality at C-3 of the shikimate nucleus has been developed and has allowed the synthesis of (−)-3(R)-amino-4(R),5(R)-dihydroxy-1-cyclohexene-1-carboxylic acid [the 3(R)-amino analogue of (−)-shikimic acid] in seven steps from the parent acid.

  已经开发出第一种成功的方法，用于在sh草酸核的C-3处引入含氮官能团，并允许合成（-）-3（R）-氨基-4（R），5（R）-二羟基- 1-环己烯-1-羧酸[ （-）-草酸的3（R）-氨基类似物]从母体酸起经过七个步骤。