((4R,5S)-5-allyl-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)methanol | 1620219-04-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ((4R,5S)-5-allyl-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)methanol
• CAS: 1620219-04-6
• 化学式: C₁₆H₂₂O₄
• 分子量: 278.348
• InChiKey: MLLBMFDGCYIFGS-AQOJYXMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.92
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ((4R,5S)-5-allyl-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)methanol 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 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 19.0h， 生成 (4R,5S)-5-allyl-2-(4-methoxyphenyl)-5-methyl-N-(3-oxo-3-(pentylamino)propyl)-1,3-dioxane-4-carboxamide
  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：

  (2R,3R)-diethyl 2-allyl-3-hydroxy-2-methylsuccinate 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 18.0h， 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