Ac-Hyp-OBn

• 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: Ac-Hyp-OBn
• 英文别名: benzyl (2S,4R)-1-acetyl-4-hydroxypyrrolidine-2-carboxylate
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: GNIWKZNGRNOCGO-OLZOCXBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ac-Hyp-OBn 在 palladium 10% on activated carbon 、 氢气 、 copper(II) sulfate 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 0.25h， 生成
  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

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。
• [EN] BOROPEPTIDE INHIBITORS OF THROMBIN WHICH CONTAIN A SUBSTITUTED PYRROLIDINE RING<br/>[FR] INHIBITEURS BOROPEPTIDIQUES DE LA THROMBINE CONTENANT UN NOYAU DE PYRROLIDINE SUBSTITUE
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：WO1995009859A1

  公开（公告）日：1995-04-13

  (EN) This invention relates to the discovery of novel and useful $g(a)-amino acid analogs, and the pharmaceutically acceptable salts and prodrugs thereof, containing a disubstituted pyrrolidine ring conjugated to an $g(a)-amino acid, useful as inhibitors of thrombin.(FR) L'invention concerne la découverte de nouveaux analogues d'$g(a)-aminoacide, ainsi que leurs sels et promédicaments acceptables pharmaceutiquement, contenant un noyau de pyrrolidine disubstitué conjugué à un $g(a)-aminoacide, qui sont efficaces en tant qu'inhibiteurs de la thrombine.
• Conformational Changes Associated with Post-Translational Modifications of Pro¹⁴³ in Skp1 of <i>Dictyostelium</i>—A Dipeptide Model System
  作者：Chamini V. Karunaratne、Thomas K. Weldeghiorghis、Christopher M. West、Carol M. Taylor

  DOI：10.1021/ja5033277

  日期：2014.10.29

  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.