(3aR,4R,6S,7aR)-4-((R)-2-Amino-1-hydroxy-ethyl)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyran-6-carboxylic acid methyl ester | 118715-03-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aR,4R,6S,7aR)-4-((R)-2-Amino-1-hydroxy-ethyl)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyran-6-carboxylic acid methyl ester
• CAS: 118715-03-0
• 化学式: C₁₂H₂₁NO₆
• 分子量: 275.302
• InChiKey: BMFBOAJDAYGGAU-HOTMZDKISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.84
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  100.24
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (3aR,4R,6S,7aR)-4-((R)-2-Amino-1-hydroxy-ethyl)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyran-6-carboxylic acid methyl ester 在 lithium hydroxide 、 N,N-bis[2-oxo-3-oxazolidinyl]phosphorodiamidic chloride 、 4-甲基苯磺酸吡啶 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 101.0h， 生成 <8-(methyldithio)-1-naphthyl>methyl 8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonate
  参考文献：
  名称：

  A novel prodrug of an impermeant inhibitor of 3-deoxy-D-manno-2-octulosonate cytidylyltransferase has antibacterial activity

  摘要：

  Although 8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonic acid (2) is a potent inhibitor of 3-deoxy-D-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase), it is unable to reach its cytoplasmic target and is therefore inactive as an antibacterial agent. However, esterification of 2 with 8-(hydroxymethyl)-1-naphthyl methyl disulfide (8) generates a prodrug (12), which gains entry into bacterial cells. Intracellular reduction of the disulfide leads to a rapid, intramolecular, displacement of the acid 2, which then inhibits the growth of Gram-negative bacteria by interfering with the biosynthesis of lipopolysaccharide.

  DOI：

  10.1021/jm00123a021
• 作为产物：
  描述：

  (3aR,4R,6S,7aR)-4-((R)-2-Azido-1-hydroxy-ethyl)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyran-6-carboxylic acid methyl ester 在 palladium on activated charcoal 氢气 作用下， 反应 3.0h， 以100%的产率得到(3aR,4R,6S,7aR)-4-((R)-2-Amino-1-hydroxy-ethyl)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyran-6-carboxylic acid methyl ester
  参考文献：
  名称：

  A novel prodrug of an impermeant inhibitor of 3-deoxy-D-manno-2-octulosonate cytidylyltransferase has antibacterial activity

  摘要：

  Although 8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonic acid (2) is a potent inhibitor of 3-deoxy-D-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase), it is unable to reach its cytoplasmic target and is therefore inactive as an antibacterial agent. However, esterification of 2 with 8-(hydroxymethyl)-1-naphthyl methyl disulfide (8) generates a prodrug (12), which gains entry into bacterial cells. Intracellular reduction of the disulfide leads to a rapid, intramolecular, displacement of the acid 2, which then inhibits the growth of Gram-negative bacteria by interfering with the biosynthesis of lipopolysaccharide.

  DOI：

  10.1021/jm00123a021