(5S,1'S)-1-(N-tert-butyloxycarbonylprolyl)-5-methylpyrrol-2(5H)-one | 174389-47-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (5S,1'S)-1-(N-tert-butyloxycarbonylprolyl)-5-methylpyrrol-2(5H)-one
• 英文别名: tert-butyl (2S)-2-[(2S)-2-methyl-5-oxo-2H-pyrrole-1-carbonyl]pyrrolidine-1-carboxylate
• CAS: 174389-47-0
• 化学式: C₁₅H₂₂N₂O₄
• 分子量: 294.351
• InChiKey: MFHWXYAYTUPKIU-QWRGUYRKSA-N

物化性质

• 沸点：
  434.7±45.0 °C(predicted)
• 密度：
  1.207±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5S,1'S)-1-(N-tert-butyloxycarbonylprolyl)-5-methylpyrrol-2(5H)-one 在 盐酸 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 Acetic acid (1R,2S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-1-methyl-2-(methyl-{(S)-2-methyl-1-[(S)-2-((S)-2-methyl-5-oxo-2,5-dihydro-pyrrole-1-carbonyl)-pyrrolidine-1-carbonyl]-propyl}-carbamoyl)-ethyl ester
  参考文献：
  名称：

  Developing microcolin A analogs as biological probes

  摘要：

  Three microcolin A and B analogs have been synthesized. Their biological activity profiles were evaluated against several cell lines, revealing the existence of a structural determinant whose role in mediating the antiproliferative effect of the microcolins has heretofore gone unrecognized. While previously described as potent immunosuppressive natural products, we found that these microcolin analogs possessed no selective cytotoxicity when comparing immune cell versus nonimmune cell proliferation. In addition, the amino-terminus of microcolin A has been modified to incorporate a biotinylated polyethylene glycol linker. The biological activity of this biotinylated microcolin A analog was determined. This affinity reagent was shown to retain limited biological activity and thus can serve as a useful probe for elucidating the mechanism of action of microcolin A. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.020
• 作为产物：
  描述：

  (S)-5-甲基吡咯烷-2-酮 在 palladium on activated charcoal 正丁基锂 、 苯基溴化硒 、 氢气 、 双氧水 、 溶剂黄146 、 lithium diisopropyl amide 作用下， 以 甲醇 为溶剂， 反应 5.92h， 生成 (5S,1'S)-1-(N-tert-butyloxycarbonylprolyl)-5-methylpyrrol-2(5H)-one
  参考文献：
  名称：

  Synthesis of Microcolin B, a Potent New Immunosuppressant Using an Efficient Mixed Imide Formation Reaction

  摘要：

  Microcolin B, a potent new immunosuppressant isolated from blue-green alga Lyngbya majuscula off the Venezuelan coast, has been made using a methyl-directed asymmetric hydrogenation reaction with rhodium on alumina catalyst on lactone 4 for the synthesis of the key (R,R)-2,4-dimethyloctanoic acid fragment 1. A new, direct mixed imide formation reaction was also developed for the production of the unusual prolylpyrrolen-2-one 2 portion of microcolin. The pentafluorophenyl ester of CBZ-proline 5 was reacted with the lithium imidate of lactam 6, providing the mixed imide in 80% yield. Coupling of acid 1 with the N-terminus of the tripeptide, followed by coupling with pyrrolylproline 2, gave microcolin B. The new mixed-imide forming reaction was also applied to a formal total synthesis of microcolin A. The pentafluorophenyl ester of TBS-protected cis-hydroxyproline was coupled with lactam 6, and the resultant imide was converted to the key pyrrolylproline made previously far microcolin A.

  DOI：

  10.1021/jo970387x

文献信息

• Synthesis of <scp>Anti‐Pancreatic</scp> Cancer Natural Product Majusculamide D and Analogues Reveals a Preliminary <scp>Structure‐Activity</scp> Relationships
  作者：Xiuhe Zhao、Mengxue Lv、Xiaonan Xi、Yaxin Lu、Liang Wang、Yue Chen

  DOI：10.1002/cjoc.202300526

  日期：2024.3.15

  The total synthesis of majusculamide D (1) was achieved from commercially available materials. In addition, we synthesized eight analogues including three stereoisomers of majusculamide D that differ in the fatty acid chain. Six analogues including a simplified analogue 29 exhibited significant nanomolar-level IC50 values against Panc-1 cells in MTT assays. A preliminary SAR analysis indicated that

  majusculamide D ( 1 )的全合成是由市售材料实现的。此外，我们还合成了八种类似物，包括三种脂肪酸链不同的 majusculamide D 立体异构体。在 MTT 测定中，包括简化类似物29在内的六种类似物对 Panc-1 细胞表现出显着的纳摩尔水平 IC 50值。初步的SAR分析表明majusculamide D的C 10 和C 2− C 3 不饱和双键上的羟基对于维持对Panc-1细胞的高活性以及C 40-Me 和C 42-Me基团的定向至关重要是可以忍受的。
• N-Benzyloxymalimide for an easy access to 5-alkyl-3-pyrrolin-2-ones: asymmetric synthesis of the mixed imide substructure of the potent immunosuppressant microcolin B
  作者：Zhao-Bao Ye、Jie Chen、Wei-Hua Meng、Pei-Qiang Huang

  DOI：10.1016/j.tetasy.2010.04.063

  日期：2010.4

  O-Benzyl-N-benzyloxymalimide 12 has been synthesized as a useful variant of the chiral building blocks 9. The advantage of the malimide 12 over 9 was demonstrated by mild and high-yielding reductive N-deprotection of N-benzyloxylactams 18a-i to give a series of (4R,5S)-5-alkyl-4-hydroxy-pyrrolidin-2-ones, which are key intermediates for the asymmetric synthesis of pyrrolidines, pyrrolizidines, and indolizidines, as well as beta-hydroxy gamma-amino acids. Lactam ent-11a has been applied to the synthesis of the mixed imide 25, a key intermediate for the total synthesis of microcolin B, which also demonstrated that lactam ent-11a or 11a can serve as a latent form of the 5-methyl-3-pyrrolin-2-one substructure of majusculamide D 4, deoxymajusculamide D, and the jamaicamides A-C. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of Microcolin B, a Potent New Immunosuppressant Using an Efficient Mixed Imide Formation Reaction
  作者：Merritt B. Andrus、Wenke Li、Robert F. Keyes

  DOI：10.1021/jo970387x

  日期：1997.8.1

  Microcolin B, a potent new immunosuppressant isolated from blue-green alga Lyngbya majuscula off the Venezuelan coast, has been made using a methyl-directed asymmetric hydrogenation reaction with rhodium on alumina catalyst on lactone 4 for the synthesis of the key (R,R)-2,4-dimethyloctanoic acid fragment 1. A new, direct mixed imide formation reaction was also developed for the production of the unusual prolylpyrrolen-2-one 2 portion of microcolin. The pentafluorophenyl ester of CBZ-proline 5 was reacted with the lithium imidate of lactam 6, providing the mixed imide in 80% yield. Coupling of acid 1 with the N-terminus of the tripeptide, followed by coupling with pyrrolylproline 2, gave microcolin B. The new mixed-imide forming reaction was also applied to a formal total synthesis of microcolin A. The pentafluorophenyl ester of TBS-protected cis-hydroxyproline was coupled with lactam 6, and the resultant imide was converted to the key pyrrolylproline made previously far microcolin A.
• Developing microcolin A analogs as biological probes
  作者：Amit K. Mandal、John Hines、Kouji Kuramochi、Craig M. Crews

  DOI：10.1016/j.bmcl.2005.06.020

  日期：2005.9

  Three microcolin A and B analogs have been synthesized. Their biological activity profiles were evaluated against several cell lines, revealing the existence of a structural determinant whose role in mediating the antiproliferative effect of the microcolins has heretofore gone unrecognized. While previously described as potent immunosuppressive natural products, we found that these microcolin analogs possessed no selective cytotoxicity when comparing immune cell versus nonimmune cell proliferation. In addition, the amino-terminus of microcolin A has been modified to incorporate a biotinylated polyethylene glycol linker. The biological activity of this biotinylated microcolin A analog was determined. This affinity reagent was shown to retain limited biological activity and thus can serve as a useful probe for elucidating the mechanism of action of microcolin A. (c) 2005 Elsevier Ltd. All rights reserved.