(R)-N-Fmoc-leucinal

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (R)-N-Fmoc-leucinal
• 英文别名: Fmoc-leucinal；D-Leu；Fmoc-D-Leu-H；9H-fluoren-9-ylmethyl N-[(2R)-4-methyl-1-oxopentan-2-yl]carbamate
• 化学式: C₂₁H₂₃NO₃
• 分子量: 337.419
• InChiKey: NTFTULBKHJJQAW-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-N-Fmoc-leucinal 在 吡啶 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.17h， 生成
  参考文献：
  名称：

  作为蛋白质-蛋白质相互作用的强效抑制剂的右手 d-Sulfono-γ-AApeptide 螺旋折叠体的合理设计和合成。

  摘要：

  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。

  DOI：

  10.1021/acs.joc.0c00996
• 作为产物：
  描述：

  Fmoc-D-亮氨酸 在 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (R)-N-Fmoc-leucinal
  参考文献：
  名称：

  Dynamic Control of Cyclic Peptide Assembly to Form Higher‐Order Assemblies

  摘要：

  摘要 手性校正、不对称、环链同分异构和分层组装是自然界的基本现象。它们与几何相关，可能会影响蛋白质或其他超分子的生物学作用。由于显示这些特征的复杂性，在人工系统中研究这些行为具有挑战性。在此，我们设计了一种交替的 D、L 肽，以重现并验证在水中环化之前自然发生的手性反转。由此产生的不对称环肽含有一个 4-咪唑烷酮环，为研究环链同分异构、纳米结构的热稳定性和动态组装提供了一个绝佳的平台。与传统的环状 D、L 肽不同，4-咪唑烷酮的形成促进了相互交织的纳米结构的形成。对纳米结构的分析证实了其左旋性，这代表了手性诱导的自组装。这证明了合理设计的多肽可以模拟多种自然现象，并能促进功能性生物材料、催化剂、抗生素和超分子的开发。

  DOI：

  10.1002/anie.202303455

文献信息

• Discovery of a Novel Class of Potent HCV NS4B Inhibitors: SAR Studies on Piperazinone Derivatives
  作者：Ramesh Kakarla、Jian Liu、Devan Naduthambi、Wonsuk Chang、Ralph T. Mosley、Donghui Bao、Holly M. Micolochick Steuer、Meg Keilman、Shalini Bansal、Angela M. Lam、William Seibel、Sandra Neilson、Phillip A. Furman、Michael J. Sofia

  DOI：10.1021/jm4012643

  日期：2014.3.13

  HTS screening identified compound 2a (piper-azinone derivative) as a low micromolar HCV genotype 1 (GT-1) inhibitor. Resistance mapping studies suggested that this piperazinone chemotype targets the HCV nonstructural protein NS4B. Extensive SAR studies were performed around 2a and the amide function and the C-3/C-6 cis stereochemistry of the piperazinone core were essential for HCV activity. A 10-fold increase in GT-1 potency was observed when the chiral phenylcyclopropyl amide side chain of 2a was replaced with p-fluorophenylisoxazole-carbonyl moiety (67). Replacing the C-6 nonpolar hydrophobic moiety of 67 with a phenyl moiety (95) did not diminish the GT-1 potency. A heterocyclic thiophene moiety (103) and an isoxazole moiety (108) were incorporated as isosteric replacements for the C-6 phenyl moiety (95), resulting in significant improvement in GT-1b and la potency. However, the piperazonone class of compounds lacks GT-2 activity and, consequently, were not pursued further into development.
• 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.
• Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3
  作者：Pijus K. Mandal、Zhiyong Ren、Xiaomin Chen、Chiyi Xiong、John S. McMurray

  DOI：10.1021/jm901105k

  日期：2009.10.8

  In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gin mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date.
• Probing the Physicochemical Boundaries of Cell Permeability and Oral Bioavailability in Lipophilic Macrocycles Inspired by Natural Products
  作者：Andrew T. Bockus、Katrina W. Lexa、Cameron R. Pye、Amit S. Kalgutkar、Jarret W. Gardner、Kathryn C. R. Hund、William M. Hewitt、Joshua A. Schwochert、Emerson Glassey、David A. Price、Alan M. Mathiowetz、Spiros Liras、Matthew P. Jacobson、R. Scott Lokey

  DOI：10.1021/acs.jmedchem.5b00128

  日期：2015.6.11

  Cyclic peptide natural products contain a variety of conserved, nonproteinogenic structural elements such as D-amino acids and amide N-methylation. In addition, many cyclic peptides incorporate gamma-amino acids and other elements derived from polyketide synthases. We hypothesized that the position and orientation Of these extended backbone elements impact the ADME properties of these hybrid molecules, especially their ability to cross cell membranes. and avoid metabolic degradation. Here we report the synthesis of cyclic hexapeptide diastereomers containing gamma-amino acids (e.g., statines) and systematically investigate their structure permeability relationships. These compounds were much more water-soluble and, in many cases, were both more membrane permeable and mote stable to liver microsomes than a similar non-statine-containing derivative. Permeability correlated well with the extent of intramolecular hydrogen bonding observed in the solution structures determined in the low-dielectric solvent CDCl3, and one compound showed an oral bioavailability of 21% in rat. Thus, the incorporation of gamma-amino acids offers a route to increase backbone diversity and improve ADME properties in cyclic peptide scaffolds.
• An enantio- and stereocontrolled route to epopromycin B via cinchona alkaloid-catalyzed Baylis–Hillman reaction
  作者：Yoshiharu Iwabuchi、Tatsuya Sugihara、Tomoyuki Esumi、Susumi Hatakeyama

  DOI：10.1016/s0040-4039(01)01676-8

  日期：2001.10

  An enantio- and stereocontrolled route to epopromycin B having the epoxy-beta -aminoketone pharmacophore is developed based on the cinchona alkaloid-catalyzed Baylis-Hillman reaction of N-Fmoc-leucinal. (C) 2001 Elsevier Science Ltd. All rights reserved.