(2R,3S)-diethyl 3-hydroxy-2-isobutyl-2-methylsuccinate | 1620219-10-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2R,3S)-diethyl 3-hydroxy-2-isobutyl-2-methylsuccinate
• CAS: 1620219-10-4
• 化学式: C₁₃H₂₄O₅
• 分子量: 260.331
• InChiKey: IEUTZWXRPICNJW-ZWNOBZJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.53
• 重原子数：
  18.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  72.83
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (2R,3S)-diethyl 3-hydroxy-2-isobutyl-2-methylsuccinate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 以81%的产率得到(R)-diethyl 2-isobutyl-2-methyl-3-oxosuccinate
  参考文献：
  名称：

  Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity

  摘要：

  Pantothenamides are N-substituted pantothenate derivatives which are known to exert antimicrobial activity through interference with coenzyme A (CoA) biosynthesis or downstream CoA-utilizing proteins. A previous report has shown that replacement of the ProR methyl group of the benchmark N-pentylpantothenamide with an allyl group (R-anti configuration) yielded one of the most potent antibacterial pantothenamides reported so far (MIC of 3.2 mu M for both sensitive and resistant Staphylococcus aureus). We describe herein a synthetic route for accessing the corresponding R-syn diastereomer using a key diastereoselective reduction with Baker's yeast, and report on the scope of this reaction for modified systems. Interestingly, whilst the R-anti diastereomer is the only one to show antibacterial activity, the R-syn isomer proved to be significantly more potent against the malaria parasite (IC50 of 2.4 +/- 0.2 mu M). Our research underlines the striking influence that stereochemistry has on the biological activity of pantothenamides, and may find utility in the study of various CoA-utilizing systems. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.06.013
• 作为产物：
  描述：

  碘代异丁烷 、 diethyl (2S,3SR)-3-methylmalate 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以81%的产率得到(2R,3S)-diethyl 3-hydroxy-2-isobutyl-2-methylsuccinate
  参考文献：
  名称：

  Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity

  摘要：

  Pantothenamides are N-substituted pantothenate derivatives which are known to exert antimicrobial activity through interference with coenzyme A (CoA) biosynthesis or downstream CoA-utilizing proteins. A previous report has shown that replacement of the ProR methyl group of the benchmark N-pentylpantothenamide with an allyl group (R-anti configuration) yielded one of the most potent antibacterial pantothenamides reported so far (MIC of 3.2 mu M for both sensitive and resistant Staphylococcus aureus). We describe herein a synthetic route for accessing the corresponding R-syn diastereomer using a key diastereoselective reduction with Baker's yeast, and report on the scope of this reaction for modified systems. Interestingly, whilst the R-anti diastereomer is the only one to show antibacterial activity, the R-syn isomer proved to be significantly more potent against the malaria parasite (IC50 of 2.4 +/- 0.2 mu M). Our research underlines the striking influence that stereochemistry has on the biological activity of pantothenamides, and may find utility in the study of various CoA-utilizing systems. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.06.013