(R)-diethyl 2-allyl-2-methyl-3-oxosuccinate | 1620219-02-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: (R)-diethyl 2-allyl-2-methyl-3-oxosuccinate
• CAS: 1620219-02-4
• 化学式: C₁₂H₁₈O₅
• 分子量: 242.272
• InChiKey: IMQPIIQJWMNHQI-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.26
• 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：
  0.58
• 拓扑面积：
  69.67
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R)-diethyl 2-allyl-2-methyl-3-oxosuccinate 在 lithium aluminium tetrahydride 、 camphor-10-sulfonic acid 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 ((4R,5S)-5-allyl-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)methanol
  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：

  (2S,3R)-3-allyl-3-methylaepfelsaeure-diethylester 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84%的产率得到(R)-diethyl 2-allyl-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

文献信息

• Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity
  作者：Annabelle Hoegl、Hamed Darabi、Elisa Tran、Emelia Awuah、Eleanor S.C. Kerdo、Eric Habib、Kevin J. Saliba、Karine Auclair

  DOI：10.1016/j.bmcl.2014.06.013

  日期：2014.8

  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.