(2S,4S)-2-[4-(Allyloxycarbonylamino-methyl)-phenyl]-4-mercapto-pyrrolidine-1-carboxylic acid allyl ester | 262846-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2S,4S)-2-[4-(Allyloxycarbonylamino-methyl)-phenyl]-4-mercapto-pyrrolidine-1-carboxylic acid allyl ester
• CAS: 262846-09-3
• 化学式: C₁₉H₂₄N₂O₄S
• 分子量: 376.477
• InChiKey: DALXJQMSTBEHLO-IRXDYDNUSA-N

物化性质

• 沸点：
  540.7±50.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.47
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  67.87
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (2S,4S)-2-[4-(Allyloxycarbonylamino-methyl)-phenyl]-4-mercapto-pyrrolidine-1-carboxylic acid allyl ester 在 bis-triphenylphosphine-palladium(II) chloride 三正丁基氢锡 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 (1R,5S,6S)-2-[(3S,5S)-5-(4-aminomthylphenyl)pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride
  参考文献：
  名称：

  Discovery of novel trans -3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems

  摘要：

  Novel trans-3,5-disubstituted pyrrolidinylthio-1 beta-methylcarbapenems were designed and synthesized to provide J-111,347 (la) as the first example of an exceptionally broad-spectrum antibiotic, showing activity against methicillin-resistant Sta-phyloccocus aureus (MRSA) phyloccocus aureus (MRSA) as well as Pseudomonas aeruginosa. Further derivation of 1a afforded J-111,225 (2a), J-114,870 (3a), and J-114,871 (3b), which showed improved safety profiles and retained broad-spectrum antibacterial activities. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00125-5
• 作为产物：
  描述：

  1-溴-4-叔丁基二甲基硅烷氧甲基苯 在 咪唑 、 盐酸 、 sodium hydroxide 、 正丁基锂 、 sodium azide 、 TEA 、 potassium tert-butylate 、 四丁基氟化铵 、 水 、 对甲苯磺酸 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,4S)-2-[4-(Allyloxycarbonylamino-methyl)-phenyl]-4-mercapto-pyrrolidine-1-carboxylic acid allyl ester
  参考文献：
  名称：

  反式-3,5-二取代的吡咯烷基硫基-1β-甲基卡巴培南的结构-活性关系。第1部分：J-111,347和相关化合物。

  摘要：

  设计并合成了在C-2处具有各种3,5-二取代的吡咯烷基硫基侧链的1-甲基-碳烯酮。对它们的抗菌活性的评估表明，J-111,347（1a）是极宽谱抗生素的第一个实例，显示出对耐甲氧西林的金黄色葡萄球菌（MRSA）以及铜绿假单胞菌的活性。

  DOI：

  10.1016/s0960-894x(99)00657-5

文献信息

• Structure–Activity Relationships of 1β-Methyl-2-(5-phenylpyrrolidin-3-ylthio)carbapenems
  作者：Hiroki Sato、Hiroki Sakoh、Takashi Hashihayata、Hideaki Imamura、Norikazu Ohtake、Aya Shimizu、Yuichi Sugimoto、Shunji Sakuraba、Rie Bamba-Nagano、Koji Yamada、Terutaka Hashizume、Hajime Morishima

  DOI：10.1016/s0968-0896(01)00430-8

  日期：2002.5

  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.