(2R,4R)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-[4-(hydroxymethyl)phenyl]pyrrolidine | 228267-23-0

• 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: (2R,4R)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-[4-(hydroxymethyl)phenyl]pyrrolidine
• 英文别名: tert-butyl (2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-2-[4-(hydroxymethyl)phenyl]pyrrolidine-1-carboxylate
• CAS: 228267-23-0
• 化学式: C₂₂H₃₇NO₄Si
• 分子量: 407.626
• InChiKey: HQCQKKNKUPECIN-RTBURBONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,4R)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-[4-(hydroxymethyl)phenyl]pyrrolidine 在 TEA 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.75h， 生成 tert-butyl (2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-2-[4-(methylaminomethyl)phenyl]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Practical Synthesis of a 1.BETA.-Methylcarbapenem, J-111,225, Using 4-Mercapto-2-[4-(N-methylaminomethyl)phenyl] pyrrolidine as a Precursor.

  摘要：

  成功开发了一种高效且实用的J-111、225 (1)合成方法，这是一种新的1β-甲基碳青霉烯。该方法以4-巯基-2-[4-(N-甲基氨基甲基)苯基]吡咯烷 (2a)为前体，通过2a与对硝基苄基 (PNB)保护的1β-甲基碳青霉烯烯醇磷酸酯3a的耦合反应，并随后移除PNB基团，与使用带有氨基保护基团的C-2侧链硫醇的常规方法相比，显著提高了J-111、225 (1)的产率。

  DOI：

  10.1248/cpb.49.476
• 作为产物：
  描述：

  (2R,4R)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-(4-formylphenyl)pyrrolidine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以91.1%的产率得到(2R,4R)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-[4-(hydroxymethyl)phenyl]pyrrolidine
  参考文献：
  名称：

  Practical Synthesis of a 1.BETA.-Methylcarbapenem, J-111,225, Using 4-Mercapto-2-[4-(N-methylaminomethyl)phenyl] pyrrolidine as a Precursor.

  摘要：

  成功开发了一种高效且实用的J-111、225 (1)合成方法，这是一种新的1β-甲基碳青霉烯。该方法以4-巯基-2-[4-(N-甲基氨基甲基)苯基]吡咯烷 (2a)为前体，通过2a与对硝基苄基 (PNB)保护的1β-甲基碳青霉烯烯醇磷酸酯3a的耦合反应，并随后移除PNB基团，与使用带有氨基保护基团的C-2侧链硫醇的常规方法相比，显著提高了J-111、225 (1)的产率。

  DOI：

  10.1248/cpb.49.476

文献信息

• Practical Synthesis of a 1.BETA.-Methylcarbapenem, J-111,225, Using 4-Mercapto-2-[4-(N-methylaminomethyl)phenyl] pyrrolidine as a Precursor.
  作者：Hideaki IMAMURA、Aya SHIMIZU、Hiroki SATO、Yuichi SUGIMOTO、Shunji SAKURABA、Koji YAMADA、Hajime MORISHIMA

  DOI：10.1248/cpb.49.476

  日期：——

  An effective and practical procedure for the synthesis of J-111, 225 (1), a new 1β-methylcarbapenem, was developed using 4-mercapto-2-[4-(N-methylaminomethyl)phenyl]pyrrolidine (2a) as a precursor. The coupling reaction of 2a with p-nitrobenzyl (PNB)-protected 1β-methylcarbapenem enolphosphate 3a and successive removal of PNB group afforded J-111, 225 (1) in significantly increased yield compared to the ordinary procedure using a C-2 side-chain thiol with amino-protective groups.

  成功开发了一种高效且实用的J-111、225 (1)合成方法，这是一种新的1β-甲基碳青霉烯。该方法以4-巯基-2-[4-(N-甲基氨基甲基)苯基]吡咯烷 (2a)为前体，通过2a与对硝基苄基 (PNB)保护的1β-甲基碳青霉烯烯醇磷酸酯3a的耦合反应，并随后移除PNB基团，与使用带有氨基保护基团的C-2侧链硫醇的常规方法相比，显著提高了J-111、225 (1)的产率。
• A Novel 1.BETA.-Methylcarbapenem, J-111,225: Effects of the C-3 and C-5 Stereochemistry of the Pyrrolidinylthio Side Chain on Antibacterial Activities.
  作者：HIDEAKI IMAMURA、AYA SHIMIZU、HIROKI SATO、YUICHI SUGIMOTO、SHUNJI SAKURABA、RIE NAGANO、KOJI YAMADA、TERUTAKA HASHIZUME、HAJIME MORISHIMA

  DOI：10.7164/antibiotics.53.314

  日期：——
• 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.