(3R,4s)-1-boc-4-Fmoc-氨基-3-吡咯烷羧酸 | 267230-44-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (3R,4s)-1-boc-4-Fmoc-氨基-3-吡咯烷羧酸
• 中文别名: (3R,4S)-1-BOC-4-FMOC-氨基-3-吡咯烷羧酸
• 英文名称: Fmoc-(R,S)-3-amino-Boc-pyrrolidine-4-carboxylic acid
• 英文别名: Fmoc-APC(Boc)；(3S,4R)-1-(N-tert-butoxycarbonyl)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-hydroxycarbonylpyrrolidine；(3S,4R)-1-(N-tert-butoxycarbonyl)-3-(9H-fluoren-9-yl-methoxycarbonylamino)pyrrolidine-4-carboxylic acid；(3R,4S)-4-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-1-(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid；(3R,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-3-carboxylic acid
• CAS: 267230-44-4
• 化学式: C₂₅H₂₈N₂O₆
• 分子量: 452.507
• InChiKey: MDJLYIHNKUJSBA-TZIWHRDSSA-N

物化性质

• 沸点：
  650.2±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  三氟乙酸五氟苯酯 、 (3R,4s)-1-boc-4-Fmoc-氨基-3-吡咯烷羧酸 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以66%的产率得到(3S,4R)-1-(N-tert-butoxycarbonyl)-3-(9H-fluoren-9-yl-methoxycarbonylamino)pyrrolidine-4-carboxylic acid pentafluorophenyl ester
  参考文献：
  名称：

  3-Aminopyrrolidine-4-carboxylic acid as versatile handle for internal labeling of pyrrolidinyl PNA

  摘要：

  Conformationally restricted pyrrolidinyl PNAs with an alpha/beta-dipeptide backbone consisting of a nucleobase-modified proline and a cyclic five-membered amino acid spacer such as (1S,2S)-2-aminocyclopentanecarboxylic acid (ACPC) (acpcPNA) can form very stable hybrids with DNA with high Watson-Crick base pairing specificity. This work aims to explore the effect of incorporating 3-aminopyrrolidine-4-carboxylic acid (APC), which is isosteric to the ACPC spacer, into the acpcPNA. It is expected that the modification should not negatively affect the DNA binding properties, and that the additional nitrogen atom in the APC should provide a handle for internal modification. Orthogonally-protected (N-3-Fmoc/N-1-Boc and N-3-Fmoc/N-1-Tfa) APC monomers have been successfully synthesized and incorporated into the acpcPNA by Fmoc-solid-phase peptide synthesis. T-m, UV and CD spectroscopy confirmed that the (3R,4S)-APC could substitute the (1S,2S)-ACPC spacer in the acpcPNA with only slightly decreasing the stability of the hybrids formed between the modified acpc/apcPNA and DNA. In contrast, the (3S,4R) enantiomer of APC caused substantial destabilization of the hybrids. Furthermore, a successful on-solid-support internal labeling of the acpc/apcPNA via amide bond formation between pyrene-1-carboxylic acid or 4-(pyrene-1-yl) butyric acid and the pyrrolidine nitrogen atom of the APC spacer has been demonstrated. Fluorescence properties of the pyrene-labeled acpc/apcPNAs are sensitive to their hybridization states and can readily distinguish between complementary and single-mismatched DNA targets. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.079
• 作为产物：
  描述：

  在 盐酸 、 palladium on activated charcoal 、 水 、 氢气 、 sodium cyanoborohydride 、 碳酸氢钠 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 生成 (3R,4s)-1-boc-4-Fmoc-氨基-3-吡咯烷羧酸
  参考文献：
  名称：

  3-Aminopyrrolidine-4-carboxylic acid as versatile handle for internal labeling of pyrrolidinyl PNA

  摘要：

  Conformationally restricted pyrrolidinyl PNAs with an alpha/beta-dipeptide backbone consisting of a nucleobase-modified proline and a cyclic five-membered amino acid spacer such as (1S,2S)-2-aminocyclopentanecarboxylic acid (ACPC) (acpcPNA) can form very stable hybrids with DNA with high Watson-Crick base pairing specificity. This work aims to explore the effect of incorporating 3-aminopyrrolidine-4-carboxylic acid (APC), which is isosteric to the ACPC spacer, into the acpcPNA. It is expected that the modification should not negatively affect the DNA binding properties, and that the additional nitrogen atom in the APC should provide a handle for internal modification. Orthogonally-protected (N-3-Fmoc/N-1-Boc and N-3-Fmoc/N-1-Tfa) APC monomers have been successfully synthesized and incorporated into the acpcPNA by Fmoc-solid-phase peptide synthesis. T-m, UV and CD spectroscopy confirmed that the (3R,4S)-APC could substitute the (1S,2S)-ACPC spacer in the acpcPNA with only slightly decreasing the stability of the hybrids formed between the modified acpc/apcPNA and DNA. In contrast, the (3S,4R) enantiomer of APC caused substantial destabilization of the hybrids. Furthermore, a successful on-solid-support internal labeling of the acpc/apcPNA via amide bond formation between pyrene-1-carboxylic acid or 4-(pyrene-1-yl) butyric acid and the pyrrolidine nitrogen atom of the APC spacer has been demonstrated. Fluorescence properties of the pyrene-labeled acpc/apcPNAs are sensitive to their hybridization states and can readily distinguish between complementary and single-mismatched DNA targets. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.079

文献信息

• 12-Helix Formation in Aqueous Solution with Short β-Peptides Containing Pyrrolidine-Based Residues
  作者：Xifang Wang、Juan F. Espinosa、Samuel H. Gellman

  DOI：10.1021/ja000093k

  日期：2000.5.1

  carboxylic acid (ACPC) residue used previously.9 Scheme 1 outlines the synthesis of enantiomerically pure (R,S)-trans-3-aminopyrrolidine-4-carboxylic acid (APC) in a protected form, from a knownâ-ketoester. 10 The key step is Michael addition of ( R)-R-methylbenzylamine to the R,â-unsaturated ester. The desired ( R,S,R) isomer was readily isolated via chromatography, and the absolute stereochemistry

  近年来，具有明确定义和可预测构象的低聚物（“折叠体”）已成为广泛关注的主题。1,2 折叠策略可用于创建特定的分子形状或功能组的特定排列，这是许多设计目标所要求的。控制形状和表面功能的传统方法涉及通常是非周期性的小型刚性骨架。相比之下，低聚物显示出高主链周期性，侧链产生官能团多样性。相对于传统支架，低聚支架的使用可以证明是有利的，因为周期性结构没有固有的尺寸限制，并且因为骨架周期性和侧链变异的组合有利于通过组合变异和选择的循环来优化分子特性。然而，大多数已知的寡聚体在构象上具有很强的流动性，至少在较短的时候（<10 个残基），这种灵活性在许多设计目标的背景下是不利的。我们描述了一组 α-氨基酸寡聚体（“α-肽”1,3），它们在水溶液中采用特定的螺旋构象，只有四个残基。水溶液中的构象稳定性对于生物学应用很重要。在常规肽（R-氨基酸残基）中，在水中的构象稳定性通常低于其他常见溶剂。4 在水溶液中检测到的非天然折叠物相对较少，5
• Synthesis and 12-Helical Secondary Structure of β-Peptides Containing (2<i>R</i>,3<i>R</i>)-Aminoproline
  作者：Emilie A. Porter、Xifang Wang、Margaret A. Schmitt、Samuel H. Gellman

  DOI：10.1021/ol0266370

  日期：2002.9.1

  (2R,3R)-Aminoproline, A pyrrolidine-based beta-amino acid, was synthesized and incorporated into hexa-beta-peptide 4. This residue confers water solubility when the ring nitrogen is protonated and allows for 12-helix formation in aqueous solution. Circular dichroism spectra display the 12-helical signature, and 12-helical structure was confirmed by 2D NMR analysis.

  (2R,3R)-Aminoproline（一种基于吡咯啶的β-氨基酸）被合成并整合到六β-肽4中。该残基在环氮质子化时赋予水溶性，并允许在水溶液中形成12股螺旋结构。圆二色光谱显示了12股螺旋的特征，而12股螺旋结构通过二维核磁共振分析得到了确认。
• Beta-amino acids
  申请人：Gellman H. Samuel

  公开号：US20070123709A1

  公开（公告）日：2007-05-31

  Disclosed are β-amino acid monomers containing cylcoalkyl, cycloalkenyl, and heterocylic substituents which encompass the α and β carbons of the peptide backbone and β-polypeptides made from such monomers. Method of generating combinatorial libraries of polypeptides containing the β-peptide residues and libraries formed thereby are disclosed.

  本发明涉及包含环烷基、环烯基和杂环取代基的β-氨基酸单体，其包括肽骨架的α和β碳，以及由这样的单体制成的β-多肽。还公开了生成含β-肽残基的多肽组合库的方法以及由此形成的库。
• Beta-polypeptides that inhibit cytomegalovirus infection
  申请人：Compton Teresa

  公开号：US20070154882A1

  公开（公告）日：2007-07-05

  Disclosed are beta-polypeptides that mimic the coiled-coil regions of gB and gH by display of the key hydrophobic residues for coiled-coil packing along one face of beta-polypeptide 12-helix. The most potent inhibitor blocks infection of CMV with an IC 50 of approximately 20 m.

  本发明揭示了一种β-多肽，通过在β-多肽12-螺旋的一个面上展示螺旋结构的关键疏水残基，模拟gB和gH的螺旋卷曲区域。其中最有效的抑制剂能够以约20 m的IC50阻止CMV的感染。
• BETA-AMINO ACIDS
  申请人：Gellman Samuel H.

  公开号：US20130023644A1

  公开（公告）日：2013-01-24

  Disclosed are β-amino acid monomers containing cylcoalkyl, cycloalkenyl, and heterocylic substituents which encompass the α and β carbons of the peptide backbone and β-polypeptides made from such monomers. Method of generating combinatorial libraries of polypeptides containing the β-peptide residues and libraries formed thereby are disclosed.

  本发明公开了含有环烷基，环烯基和杂环基取代基的β-氨基酸单体，这些取代基包括多肽骨架的α和β碳，以及由这些单体制成的β-多肽。本发明还公开了生成含有β-肽残基的多肽组合库的方法以及由此形成的库。