Fmoc-Hyp-OBn | 134262-54-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Hyp-OBn
• 英文别名: 2-O-benzyl 1-O-(9H-fluoren-9-ylmethyl) (2S,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate
• CAS: 134262-54-7
• 化学式: C₂₇H₂₅NO₅
• 分子量: 443.499
• InChiKey: CVHUWFLTKKZKSQ-CLOONOSVSA-N

物化性质

• 沸点：
  621.0±55.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Fmoc-Hyp-OBn 在 copper(II) sulfate 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 3.42h， 生成 Fmoc-[(α,1-4)GlcNAc(OAc)₄]-Hyp-OBn
  参考文献：
  名称：

  Conformational Changes Associated with Post-Translational Modifications of Pro¹⁴³ in Skp1 of Dictyostelium—A Dipeptide Model System

  摘要：

  Prolyl hydroxylation and subsequent glycosylation of the E3(SCF) ubiquitin ligase subunit Skp1 affects its conformation and its interaction with F-box proteins and, ultimately, O-2-sensing in the organism. Taking a reductionist approach to understand the molecular basis for these effects, a series of end-capped Thr-Pro dipeptides was synthesized, tracking the sequential post-translational modifications that occur in the protein. The conformation of the pyrrolidine ring in each compound was gauged via coupling constants ((3)J(H alpha,H beta)) and the electronegativity of the C gamma-substituents by chemical shifts (C-13). The equilibrium between the cis-trans conformations about the central prolyl peptide bond was investigated by integration of signals corresponding to the two species in the H-1 NMR spectra over a range of temperatures. These studies revealed an increasing preference for the trans-conformation in the order Pro < Hyp < [alpha-(1,4)GlcNAc]Hyp. Rates for the forward and reverse reactions, determined by magnetization transfer experiments, demonstrated a reduced rate for the trans-to-cis conversion and a significant increase in the cis-to-trans conversion upon hydroxylation of the proline residue in the dipeptide. NOE experiments suggest that the Thr side chain pushes the sugar away from the pyrrolidine ring. These effects, which depended on the presence of the N-terminal Thr residue, offer a mechanism to explain altered properties of the corresponding full-length proteins.

  DOI：

  10.1021/ja5033277
• 作为产物：
  描述：

  (fluorenylmethyloxycarbonyl)-L-trans-4-hydroxyproline 、 溴甲苯 在 caesium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 以94%的产率得到Fmoc-Hyp-OBn
  参考文献：
  名称：

  化学合成的Skp1衍生的糖肽用于探测蛋白质特异性糖基化

  摘要：

  Skp1是一种胞质蛋白和核蛋白，最著名的是E3泛素连接酶SCF家族的一个衔接子，为蛋白质的降解标记。双歧杆菌中的Skp1由五糖在特定的羟脯氨酸（Hyp）残基上进行翻译后修饰，该五糖由Fucα1,2-Galβ-1,3-GlcNAcα核组成，并装饰有两个α-连接的Gal残基。制备了糖肽衍生形式Skp1，以表征介导α-Gal部分添加的α-半乳糖基转移酶（AgtA），并开发出适合追踪细胞中Skp1的三糖同工型的抗体。基于2-萘甲基（Nap）醚作为永久保护基团的使用，开发了一种合成三糖-Hyp核心的策略，以允许Hyp部分的后期安装。糖基供体和受体反应性的调节对于实现糖基化的高产率和异头选择性至关重要。利用微波辅助固相肽合成法将三糖-Hyp部分用于糖肽的制备。酶动力学研究表明，AgtA无法识别三糖-Hyp和三糖-肽，这表明天然Skp1蛋白提供的与活性位点结合的环境非常重要。三糖肽是一种有效的免疫原，能

  DOI：

  10.1002/chem.201501598

文献信息

• Synthesis and Conformational Properties of 3,4-Difluoro-<scp>l</scp>-prolines
  作者：Gert-Jan Hofman、Emile Ottoy、Mark E. Light、Bruno Kieffer、Jose C. Martins、Ilya Kuprov、Davy Sinnaeve、Bruno Linclau

  DOI：10.1021/acs.joc.8b02920

  日期：2019.3.15

  monofluorination at the proline 3- or 4-position, different effects on the conformational properties of proline (ring pucker, cis/trans isomerization) are introduced. With fluorination at both 3- and 4-positions, matching or mismatching effects can occur depending on the relative stereochemistry. Here we report, in full, the syntheses and conformational properties of three out of the four possible 3,4-difluoro-l-proline

  氟化脯氨酸衍生物在医学化学，结构生物化学到有机催化等领域都有广泛的应用。根据脯氨酸3-或4-位上单氟化的立体化学，引入了对脯氨酸构象性质的不同影响（环折叠，顺式/反式异构化）。在3位和4位氟化时，取决于相对的立体化学，会发生匹配或错配的作用。在这里，我们全面报告了四种可能的3,4-二氟-1-脯氨酸非对映异构体中的三种的合成和构象性质。（3 S，4 S）-和（3R，4 R）-二氟-1-脯氨酸，显示出与它们各自的单氟化祖细胞相同的数量级上的环褶皱和顺式/反式比例，尽管酰胺的顺式/反式异构化速率明显加快。因此，所报道的类似物扩展了可用的氟化脯氨酸类似物的范围，作为调整脯氨酸独特的构象和动力学性质的工具，从而可以探究其在例如蛋白质稳定性或折叠中的作用。
• Peptidomimetics of biologically active metallopeptides
  申请人：Palatin Technologies, Inc.

  公开号：US20040171520A1

  公开（公告）日：2004-09-02

  The invention relates to a method of deriving a peptidomimetic of a biologically active metallopeptide, wherein the peptidomimetic includes at least one non-peptide ring structure defining a template space superimposable on a corresponding defined template space of the metallopeptide, and where the peptidomimetic further includes at least two elements independently including an amino acid residue, amino acid side chain moiety or derivative thereof, the elements defining and occupying a similar descriptor space as corresponding elements of the metallopeptide. The invention further relates to peptidomimetics with a template space heterocyclic ring structure, including 5-, 6- and 8-membered and 5-5- and 6-5-bicyclic fused ring structure melanocortin receptor-specific peptidomimetics.

  本发明涉及一种导出生物活性金属肽的肽类类似物的方法，其中该肽类类似物包括至少一个非肽环结构，该非肽环结构定义了一个模板空间，可以与金属肽的相应定义模板空间相重叠。肽类类似物还包括至少两个元素，这些元素独立地包括氨基酸残基、氨基酸侧链基团或其衍生物，这些元素定义并占据与金属肽的相应元素类似的描述符空间。本发明还涉及带有模板空间杂环环结构的肽类类似物，包括5、6和8个成员以及5-5-和6-5-融合环结构的黑素皮质素受体特异性肽类类似物。
• Chemical Synthesis of Glycopeptides containing <scp>l</scp>-Arabinosylated Hydroxyproline and Sulfated Tyrosine
  作者：Jasper W. van de Sande、Bauke Albada

  DOI：10.1021/acs.orglett.3c00411

  日期：2023.3.24

  the stereoselective total synthesis of β-1,2-linked l-arabinosylated Fmoc-protected hydroxyproline building blocks and their incorporation, together with sulfated tyrosine and hydroxyproline, into the plant peptide hormone PSY1. Clean glycopeptides were obtained by performing acetyl removal from the l-arabinose groups prior to deprotection of the neopentyl-protected sulfated tyrosine.

  翻译后修饰的肽是生物体的重要调节分子。在这里，我们报告了 β-1,2-连接的l-阿拉伯糖基化 Fmoc 保护的羟脯氨酸结构单元的立体选择性全合成及其与硫酸化酪氨酸和羟脯氨酸一起掺入植物肽激素 PSY1 中。在新戊基保护的硫酸化酪氨酸脱保护之前，通过从l-阿拉伯糖基团中去除乙酰基获得干净的糖肽。
• Pyrrolidine melanocortin-specific compounds
  申请人：Palatin Technologies, Inc.

  公开号：US20040167201A1

  公开（公告）日：2004-08-26

  Melanocortin receptor-specific pyrrolidine compounds having the structure: 1 and stereoisomer and pharmaceutically acceptable salts thereof, where R 1 , R 2 , and R 3 are as described in the specification, preferably where R 3 is a D-amino acid with at least one substituted or unsubstituted phenyl or naphthyl aromatic ring, and where R 3 optionally further includes an amine capping group or from one to three additional amino acid residues, optionally with an amine capping group, which compounds are agonists, antagonists or mixed agonists and antagonists at one or more melanocortin receptors, and having utility in the treatment of melanocortin receptor-related disorders and conditions. Methods of synthesis of compounds of structure (I), pharmaceutical compositions containing a compound of structure (I) and methods relating to the use thereof are also disclosed.

  具有以下结构的黑色素皮质素受体特异性吡咯烷化合物： 1 及其立体异构体和药学上可接受的盐类，其中 R 1 , R 2 和 R 3 如说明书所述，其中 R 3 是具有至少一个取代或未取代的苯基或萘基芳香环的 D-氨基酸，其中 R 3 可选地进一步包括一个胺封端基团或一至三个额外的氨基酸残基，可选地带有一个胺封端基团，这些化合物是一种或多种黑色素皮质素受体的激动剂、拮抗剂或混合激动剂和拮抗剂，在治疗黑色素皮质素受体相关疾病和病症方面具有实用性。此外，还公开了结构(I)化合物的合成方法、含有结构(I)化合物的药物组合物及其使用方法。
• Catalysis with Phosphine-Containing Amino Acids in Various “Turn” Motifs
  作者：Anton Agarkov、Scott J. Greenfield、Takahiro Ohishi、Scott E. Collibee、Scott R. Gilbertson

  DOI：10.1021/jo049103g

  日期：2004.11.1

  We have been actively involved in the development of parallel approaches for the discovery of phosphine ligands. Our approach has been based on the incorporation of phosphine-containing amino acids into peptide sequences that are designed to have stable secondary structures. We have examined helical and turn secondary structures and have reported that alkylation of cyclopentenyl acetate with dimethylmalonate can be catalyzed in high enantiomeric excess (ee) with a beta-turn-based ligand. The importance of the peptide secondary structure was demonstrated through the synthesis of a series of peptide ligands where the nature of the turn-forming residues was probed. Additionally, other turn-forming units and a variety of different phosphine-containing amino acids have been examined for their ability to control the selectivity of the allylation reaction. This paper reports the results obtained through the examination of different turn motifs as well as different phosphine substitutions on the "best" turn sequence, Pps-Pro-D-Xxx-Pps.