allyl (1R,5S,6S)-2-[(3S,5R)-5-[4-(N-allyloxycarbonylaminomethyl)cyclohexyl]-1-allyloxycarbonylpyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate | 442887-37-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: allyl (1R,5S,6S)-2-[(3S,5R)-5-[4-(N-allyloxycarbonylaminomethyl)cyclohexyl]-1-allyloxycarbonylpyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate
• CAS: 442887-37-8
• 化学式: C₃₂H₄₅N₃O₈S
• 分子量: 631.791
• InChiKey: JMPRLZRDKLELND-GFAZMJTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.0
• 重原子数：
  44.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  134.71
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  allyl (1R,5S,6S)-2-[(3S,5R)-5-[4-(N-allyloxycarbonylaminomethyl)cyclohexyl]-1-allyloxycarbonylpyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 水 、 三正丁基氢锡 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以58.6%的产率得到(1R,5S,6S)-2-[(3S,5R)-5-[4-(aminomethyl)cyclohexyl]pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride
  参考文献：
  名称：

  Structure–Activity Relationships of 1β-Methyl-2-(5-phenylpyrrolidin-3-ylthio)carbapenems

  摘要：

  Structure-activity relationship studies of 1beta-methyl-2-[(3S,5R)-5-(4-aminomethylphenyl)pyrrolidin-3-ylthio]carbapenems, especially those pertaining to the relationship between antibacterial activity and side-chain structure were conducted. These studies suggested that the trans-(3S,5R)-5-phenylpyrrolidin-3-ylthio side-chain and the aminomethyl group at the 4-position of the phenyl ring play a key role in enhancing the antibacterial activity against the MRSA and Pseudomonas aeruginosa strains. In particular, the basicity of a substituent at the 4-position of the phenyl ring were shown to greatly contribute to the antibacterial activity against MRSA and methicillin-resistant Staphlyloccocus epidermidis strains. In contrast, the amidine group was shown to lead to potent antibacterial activity against P. aeruginosa strains comparable to that of imipenem, however, a good correlation between the basicity of the 4-substituent and antipseudomonal activity was not observed. In conclusion, the 4-aminomethyl or methylaminomethyl group on the phenyl ring was the best substituent for antipseudomonal activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00430-8
• 作为产物：
  描述：

  (2S,4S)-2-[4-(N-allyloxycarbonylaminomethyl)cyclohexyl]-1-allyloxycarbonyl-4-hydroxypyrrolidine 在 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 1.83h， 生成 allyl (1R,5S,6S)-2-[(3S,5R)-5-[4-(N-allyloxycarbonylaminomethyl)cyclohexyl]-1-allyloxycarbonylpyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate
  参考文献：
  名称：

  Structure–Activity Relationships of 1β-Methyl-2-(5-phenylpyrrolidin-3-ylthio)carbapenems

  摘要：

  Structure-activity relationship studies of 1beta-methyl-2-[(3S,5R)-5-(4-aminomethylphenyl)pyrrolidin-3-ylthio]carbapenems, especially those pertaining to the relationship between antibacterial activity and side-chain structure were conducted. These studies suggested that the trans-(3S,5R)-5-phenylpyrrolidin-3-ylthio side-chain and the aminomethyl group at the 4-position of the phenyl ring play a key role in enhancing the antibacterial activity against the MRSA and Pseudomonas aeruginosa strains. In particular, the basicity of a substituent at the 4-position of the phenyl ring were shown to greatly contribute to the antibacterial activity against MRSA and methicillin-resistant Staphlyloccocus epidermidis strains. In contrast, the amidine group was shown to lead to potent antibacterial activity against P. aeruginosa strains comparable to that of imipenem, however, a good correlation between the basicity of the 4-substituent and antipseudomonal activity was not observed. In conclusion, the 4-aminomethyl or methylaminomethyl group on the phenyl ring was the best substituent for antipseudomonal activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00430-8