(R)-N-α-(fluorenylmethyloxycarbonyl)-N-ε-(tert-butyloxycarbonyl)-lysinal

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (R)-N-α-(fluorenylmethyloxycarbonyl)-N-ε-(tert-butyloxycarbonyl)-lysinal
• 英文别名: tert-butyl (R)-5-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-oxohexyl-carbamate；Fmoc-D-Lys(Boc)-Wang Resin (100-200mesh, 1% DVB)；tert-butyl N-[(5R)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-oxohexyl]carbamate
• 化学式: C₂₆H₃₂N₂O₅
• 分子量: 452.55
• InChiKey: APPXMECEIFEZAO-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N-α-(fluorenylmethyloxycarbonyl)-N-ε-(tert-butyloxycarbonyl)-lysinal 在 盐酸 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (R)-N-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-((tert-butoxycarbonyl)amino)hexyl)-N-(2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetyl)glycine
  参考文献：
  名称：

  Preparation and determination of optical purity of γ-lysine modified peptide nucleic acid analogues

  摘要：

  肽核酸（PNA）是一种 DNA 类似物，其中核酸骨架被假肽骨架取代，核碱基通过亚甲基羰基连接体连接到骨架上。-对 PNA 结构进行碳修饰可以获得性能更好的单体和低聚物。在这项研究中，我们报告了γ-赖氨酸修饰的嘧啶碱（胸腺嘧啶和胞嘧啶）PNA 单体的简便合成方法，其光学纯度高达 99.5%，并利用手性 HPLC 直接分离了γ-赖氨酸修饰的 PNA 类似物的对映体，从而确定了光学纯度。

  DOI：

  10.1007/s12272-012-0315-4
• 作为产物：
  描述：

  N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-D-赖氨酸 在 lithium aluminium tetrahydride 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-N-α-(fluorenylmethyloxycarbonyl)-N-ε-(tert-butyloxycarbonyl)-lysinal
  参考文献：
  名称：

  Preparation and determination of optical purity of γ-lysine modified peptide nucleic acid analogues

  摘要：

  肽核酸（PNA）是一种 DNA 类似物，其中核酸骨架被假肽骨架取代，核碱基通过亚甲基羰基连接体连接到骨架上。-对 PNA 结构进行碳修饰可以获得性能更好的单体和低聚物。在这项研究中，我们报告了γ-赖氨酸修饰的嘧啶碱（胸腺嘧啶和胞嘧啶）PNA 单体的简便合成方法，其光学纯度高达 99.5%，并利用手性 HPLC 直接分离了γ-赖氨酸修饰的 PNA 类似物的对映体，从而确定了光学纯度。

  DOI：

  10.1007/s12272-012-0315-4

文献信息

• Modular Solid-Phase Synthesis of Antiprotozoal Barnesin Derivatives
  作者：Dávid Roman、Luka Raguž、François Keiff、Florian Meyer、Fabian Barthels、Tanja Schirmeister、Florian Kloss、Christine Beemelmanns

  DOI：10.1021/acs.orglett.0c00723

  日期：2020.5.15

  ons reagent to prepare SP-bound vinylogous amino acids. Subsequent SP-based peptide synthesis, global deprotection, and chemical modifications yielded 14 lipodipeptides carrying vinylogous amino acids, including the natural product barnesin A (1). Biological evaluation revealed that several synthesized derivatives show micromolar to nanomolar inhibitory activity against papain-like cysteine proteases

  在这里，我们应用并优化了基于固体支持物（SP）的Horner-Wadsworth-Emmons试剂，以制备与SP结合的乙烯基氨基酸。随后的基于SP的肽合成，整体脱保护和化学修饰产生了14种带有乙烯基氨基酸的脂肽，包括天然产物Barnesin A（1）。生物学评估表明，几种合成的衍生物对木瓜蛋白酶样半胱氨酸蛋白酶，人组织蛋白酶L和罗德萨因表现出微摩尔至纳摩尔的抑制活性。
• DNA-Templated Polymerization of Side-Chain-Functionalized Peptide Nucleic Acid Aldehydes
  作者：Ralph E. Kleiner、Yevgeny Brudno、Michael E. Birnbaum、David R. Liu

  DOI：10.1021/ja0753997

  日期：2008.4.1

  The DNA-templated polymerization of synthetic building blocks provides a potential route to the laboratory evolution of sequence-defined polymers with structures and properties not necessarily limited to those of natural biopolymers. We previously reported the efficient and sequence-specific DNA-templated polymerization of peptide nucleic acid (PNA) aldehydes. Here, we report the enzyme-free, DNA-templated polymerization of side-chain-functionalized PNA tetramer and pentamer aldehydes. We observed that polymerization of tetramer and pentamer PNA building blocks with a single lysine-based side chain at various positions in the building block could proceed efficiently and sequence specifically. In addition, DNA-templated polymerization also proceeded efficiently and in a sequence-specific manner with pentamer PNA aldehydes containing two or three lysine side chains in a single building block to generate more densely functionalized polymers. To further our understanding of side-chain compatibility and expand the capabilities of this system, we also examined the polymerization efficiencies of 20 pentamer building blocks each containing one of five different side-chain groups and four different side-chain regio- and stereochemistries. Polymerization reactions were efficient for all five different side-chain groups and for three of the four combinations of side-chain regio- and stereochemistries. Differences in the efficiency and initial rate of polymerization correlate with the apparent melting temperature of each building block, which is dependent on side-chain regio- and stereochemistry but relatively insensitive to side-chain structure among the substrates tested. Our findings represent a significant step toward the evolution of sequence-defined synthetic polymers and also demonstrate that enzyme-free nucleic acid-templated polymerization can occur efficiently using substrates with a wide range of side-chain structures, functionalization positions within each building block, and functionalization densities.
• A Solid-Phase Approach to Mouse Melanocortin Receptor Agonists Derived from a Novel Thioether Cyclized Peptidomimetic Scaffold
  作者：Jon Bondebjerg、Zhimin Xiang、Rayna M. Bauzo、Carrie Haskell-Luevano、Morten Meldal

  DOI：10.1021/ja0123913

  日期：2002.9.1

  The solid-phase synthesis of a novel thioether cyclized peptidomimetic scaffold, displaying functionality at the i to i+3 positions, is reported. The thioether bridge is formed on-bead by an intramolecular reaction between a chloroacetylated reduced peptide bond and the free thiol from a cysteine. The crude products were obtained in moderate to very high purity. A series of 19 compounds were prepared and tested for agonist activity at the mouse melanocortin receptors 1, 3, 4, and 5 (mMC1-5R). From these results, several compounds were identified as having low micromolar agonist activity at the mMC1R and mMC4R. The former is involved in skin pigmentation and animal coat coloration. The latter is involved in the regulation of appetite and food intake and is currently a drug target for potential treatment of obesity. The most potent compound 1n with the pharmacophore motif "His-DPhe-Arg-Trp" was identified as having an EC50 value of 165 nM at mMC1R, 7600 nM at mMC3R, 650 nM at mMC4R, and 335 nM at mMC5R. In addition, some of the compounds showed moderate selectivity for the mMC1R.
• Rational Design and Synthesis of Right-Handed <scp>d</scp>-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein–Protein Interactions
  作者：Peng Sang、Yan Shi、Pirada Higbee、Minghui Wang、Sami Abdulkadir、Junhao Lu、Gary Daughdrill、Jiandong Chen、Jianfeng Cai

  DOI：10.1021/acs.joc.0c00996

  日期：2020.8.21

  right-handed d-sulfono-γ-AApeptides reveal much-enhanced binding affinity compared to the p53 peptide. The design of d-sulfono-γ-AApeptides may provide a new and alternative strategy to modulate protein–protein interactions.

  已经有效地设计和合成了前所未有的新型螺旋折叠器。均质右旋d-磺基-γ-AApeptides代表了新一代非天然螺旋肽模拟物，其具有与α-肽相似的折叠构象，使其成为设计α-螺旋模拟物的理想分子支架。正如 p53-MDM2 PPI 作为模型应用所证明的那样，与 p53 肽相比，右手d-磺基-γ-AApeptides 显示出大大增强的结合亲和力。d-磺基-γ-AApeptides的设计可能为调节蛋白质-蛋白质相互作用提供一种新的替代策略。
• Preparation and determination of optical purity of γ-lysine modified peptide nucleic acid analogues
  作者：Hu Huang、Goon Ho Joe、Sung Rok Choi、Su Nam Kim、Yong Tae Kim、Hwang Siek Pak、Sung Kee Kim、Joon Hee Hong、Hyo-Kyung Han、Jong Seong Kang、Wonjae Lee

  DOI：10.1007/s12272-012-0315-4

  日期：2012.3

  Peptide nucleic acids (PNAs) are DNA analogues in which the nucleic acid backbone is replaced by a pseudopeptide backbone and nucleobases are attached to the backbone by methylene carbonyl linkers. -Carbon modification of the PNA structure allows monomers, and subsequently oligomers, with improved properties to be obtained. In this study, we report the convenient synthesis of γ-lysine-modified PNA monomers for pyrimidine bases (thymine and cytosine) with high optical purity (> 99.5%) and direct enantiomer separation of γ-lysine-modified PNA analogs, using chiral HPLC to determine the optical purity.

  肽核酸（PNA）是一种 DNA 类似物，其中核酸骨架被假肽骨架取代，核碱基通过亚甲基羰基连接体连接到骨架上。-对 PNA 结构进行碳修饰可以获得性能更好的单体和低聚物。在这项研究中，我们报告了γ-赖氨酸修饰的嘧啶碱（胸腺嘧啶和胞嘧啶）PNA 单体的简便合成方法，其光学纯度高达 99.5%，并利用手性 HPLC 直接分离了γ-赖氨酸修饰的 PNA 类似物的对映体，从而确定了光学纯度。