(2R,4R)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-(4-formylphenyl)pyrrolidine | 228267-22-9

• 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-formylphenyl)pyrrolidine
• 英文别名: tert-butyl (2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-2-(4-formylphenyl)pyrrolidine-1-carboxylate
• CAS: 228267-22-9
• 化学式: C₂₂H₃₅NO₄Si
• 分子量: 405.61
• InChiKey: OGGCORAXQOJKGI-RTBURBONSA-N

物化性质

• 沸点：
  463.6±45.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.57
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 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-formylphenyl)pyrrolidine 在 palladium dihydroxide 正丁基锂 、 氢气 、 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 37.0h， 生成 (2R,4R)-4-tert-butyldimethylsiloxy-2-[4-[(S)-1-[(R)-(α-methoxy-α-trifluoromethyl)benzyl-carbonylamino]-2-ethoxycarbonylethyl]phenyl]pyrrolidine
  参考文献：
  名称：

  Stereoselective Synthesis of a Broad Spectrum 1β-Methylcarbapenem, J-114,870

  摘要：

  An ultra-broad spectrum carbapenem, J-114,870 (1), was synthesized from the corresponding C-2 side chain and 1 beta-methyl carbapenem enolphosphate. Synthesis of the C-2 side chain was accomplished by installation of the benzene part to (4R)-hydroxy-2-pyrrolidone 3, affording 2-phenylpyrrolidine 8a, and asymmetric Michael addition of chiral amine to alpha,beta-unsaturated ester derived from 8a. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00685-2
• 作为产物：
  描述：

  (2R,4R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-(4-dimethoxymethyl-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester 在 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以51 mg的产率得到(2R,4R)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-(4-formylphenyl)pyrrolidine
  参考文献：
  名称：

  Diastereoselective Synthesis of (2R,4R)-2-Aryl-4-hydroxypyrrolidine: Preparation of the Side Chain of Novel Carbapenem.

  摘要：

  通过立体选择性还原 1-芳基-1-丁酮衍生物 5 和所得手性醇 6 的连续分子内环化，改进了新型碳青霉烯 1 的反式 3,5-二取代吡咯烷-3-基硫基侧链的合成通过保护的4-羟基-2-吡咯烷酮与芳基格氏试剂的偶联反应得到1-芳基-1-丁酮衍生物5。

  DOI：

  10.1248/cpb.49.1500

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。
• Diastereoselective Allylation of a Chiral Imine with Allylzinc Reagents: Diastereoselective Synthesis of a Novel Broad Spectrum Carbapenem
  作者：Yuichi Sugimoto、Hideaki Imamura、Hiroki Sakoh、Koji Yamada、Hajime Morishima

  DOI：10.1055/s-2001-18100

  日期：——

  Diastereoselective allylation of chiral imine with allylmetal reagents was applied to prepare β-amino acid derivative as a key intermediate for the synthesis of a novel carbapenem 1. Combination of the allylzinc reagents and chiral imine, which was derived from l-valine methyl ester as a chiral auxiliary afforded a homoallylamine in good yield with excellent diastereoselectivity.

  应用烯丙基金属试剂对手性亚胺进行非对映选择性烯丙基化，制备出δ-氨基酸衍生物，作为合成新型碳青霉烯类 1 的关键中间体。将烯丙基锌试剂和手性亚胺（从 l-缬氨酸甲酯中提取）作为手性辅助剂结合在一起，就能以良好的非对映选择性获得均烯丙基胺。
• 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.
• Lipase-catalyzed kinetic resolution of ethyl 3-aryl-3-hydroxypropionate: preparation of the side chain of a novel carbapenem, J-114,870
  作者：Yuichi Sugimoto、Hideaki Imamura、Aya Shimizu、Masato Nakano、Shigeru Nakajima、Shinnosuke Abe、Koji Yamada、Hajime Morishima

  DOI：10.1016/s0957-4166(00)00326-8

  日期：2000.9

  An optically active 3-aryl-3-hydroxypropionate 3a was prepared by lipase-catalyzed kinetic hydrolysis of a diastereomeric mixture of 3-aryl-3-(alpha -chloroacetoxy)propionate 6 in good conversion yield with adequate purity (>95% de). This enzymatic reaction proceeded with great efficiency as measured by reaction rate, chemical yield and stereoselectivity. The compound 3a was converted to J-114,870 1a, a novel ultra-broad spectrum carbapenem without significant epimerization. (C) 2000 Elsevier Science Ltd. All rights reserved.
• 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：——