(2R,3R)-diethyl 2-allyl-3-hydroxy-2-methylsuccinate | 1620219-03-5

• 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,3R)-diethyl 2-allyl-3-hydroxy-2-methylsuccinate
• CAS: 1620219-03-5
• 化学式: C₁₂H₂₀O₅
• 分子量: 244.288
• InChiKey: JZMBSEMISBGGRP-JOYOIKCWSA-N

物化性质

• 沸点：
  330.0±42.0 °C(predicted)
• 密度：
  1.077±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.06
• 重原子数：
  17.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 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,3R)-diethyl 2-allyl-3-hydroxy-2-methylsuccinate 在 sodium chlorite 、 sodium dihydrogenphosphate 、 lithium aluminium tetrahydride 、 2-甲基-2-丁烯 、 camphor-10-sulfonic acid 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 41.0h， 生成 (2R,3S)-2-hydroxy-3-(hydroxymethyl)-3-methyl-N-(3-oxo-3-(pentylamino)propyl)hex-5-enamide
  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：

  (R)-diethyl 2-allyl-2-methyl-3-oxosuccinate 在 丁烯酮 作用下， 以 水 为溶剂， 反应 24.0h， 以68%的产率得到(2R,3R)-diethyl 2-allyl-3-hydroxy-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