allyl (1R,5S,6S)-2-[(3S,5R)-1-allyloxycarbonyl-5-[4-(N-allyloxycarbonylaminomethyl)phenyl]pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate | 304655-63-8

• 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)-1-allyloxycarbonyl-5-[4-(N-allyloxycarbonylaminomethyl)phenyl]pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate
• 英文别名: allyl (1R,5S,6S)-2-[(3S,5R)-1-allyloxycarbonyl-5-[4-(N-allyloxycarbonylaminomthyl)phenyl]pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate
• CAS: 304655-63-8
• 化学式: C₃₂H₃₉N₃O₈S
• 分子量: 625.743
• InChiKey: XEUGESVXEMZGSD-FYCJBKCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 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：
  0.44
• 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)-1-allyloxycarbonyl-5-[4-(N-allyloxycarbonylaminomethyl)phenyl]pyrrolidin-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 0.33h， 以72.9%的产率得到(1R,5S,6S)-2-[(3S,5R)-5-(4-aminomethylphenyl)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：

  1-溴-4-叔丁基二甲基硅烷氧甲基苯 在 N-甲基吗啉 、 sodium hydroxide 、 sodium tetrahydroborate 、 正丁基锂 、 sodium azide 、 四丙基高钌酸铵 、 TEA 、 potassium tert-butylate 、 四丁基氟化铵 、 水 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 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 、 乙腈 为溶剂， 生成 allyl (1R,5S,6S)-2-[(3S,5R)-1-allyloxycarbonyl-5-[4-(N-allyloxycarbonylaminomethyl)phenyl]pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate
  参考文献：
  名称：

  Synthesis of J-111,347, a Novel 1.BETA.-Methylcarbapenem with Broad-spectrum Antibacterial Activity.

  摘要：

  J-111, 347 (1)是一种新型 1β-甲基碳青霉烯，具有广谱抗菌活性，包括抗耐甲氧西林金黄色葡萄球菌（MRSA）和铜绿假单胞菌，其合成是通过非对映选择性地从具有光学活性的 (R)-3，4-二羟基丁醛 4 中制备侧链硫醇 3 而实现的。

  DOI：

  10.1248/cpb.48.310

文献信息

• Structure–activity relationships of trans -3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems. Part 1: J-111,347 and related compounds
  作者：Hideaki Imamura、Norikazu Ohtake、Aya Shimizu、Hideki Jona、Hiroki Sato、Rie Nagano、Ryosuke Ushijima、Koji Yamada、Terutaka Hashizume、Hajime Morishima

  DOI：10.1016/s0960-894x(99)00657-5

  日期：2000.1

  1Beta-methylcarbapenems having various 3,5-disubstituted pyrrolidinylthio-side chains at C-2 were designed and synthesized. Evaluation of their antibacterial activities indicated that J-111,347 (1a) is the first example of an extremely broad spectrum antibiotic showing activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as Pseudomonas aeruginosa.

  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。
• Discovery of novel trans -3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems
  作者：Hideaki Imamura、Norikazu Ohtake、Aya Shimizu、Hiroki Sato、Yuichi Sugimoto、Shunji Sakuraba、Rie Nagano、Masato Nakano、Shinnosuke Abe、Chihiro Suzuki-Sato、Ikuko Nishimura、Hisaki Kojima、Yoshimi Tsuchiya、Koji Yamada、Terutaka Hashizume、Hajime Morishima

  DOI：10.1016/s0968-0896(00)00125-5

  日期：2000.8

  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.