(R)-N-(benzyloxycarbonyl)-2-(2'-propenyl)proline | 121773-05-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-N-(benzyloxycarbonyl)-2-(2'-propenyl)proline
• 英文别名: (R)-α-allyl-proline；(2R)-1-phenylmethoxycarbonyl-2-prop-2-enylpyrrolidine-2-carboxylic acid
• CAS: 121773-05-5
• 化学式: C₁₆H₁₉NO₄
• 分子量: 289.331
• InChiKey: YHEBDKBWVUFDPP-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  (R)-N-(benzyloxycarbonyl)-2-(2'-propenyl)proline 在 4-二甲氨基吡啶 、 platinum(IV) oxide 、 palladium on activated charcoal 硫酸 、 氢气 、 sodium carbonate 、 臭氧 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 (3R,6R)-3-(<(9H-fluoren-9-yl)methoxycarbonyl>amino)-2-oxo-1-azabicyclo<4.3.0>nonane-6-carboxylic acid
  参考文献：
  名称：

  Design and synthesis of a cis-gly-pro, type-VI turn, dipeptide mimetic and its use in fmoc-solid phase peptide synthesis

  摘要：

  The Fmoc-protected bicyclic molecules 7 and 8 have been produced as cis-Gly-Pro peptide mimetics in nine synthetic steps starting from optically pure (R)-2-allylproline. Their use in solid-phase peptide synthesis has been demonstrated by their incorporation into analogues of cis-Gly(6)-Pro(7)-bradykinin.

  DOI：

  10.1016/s0040-4039(00)75983-1
• 作为产物：
  描述：

  (2R,5R)-5-allyl-2-tert-butyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one 在 盐酸 、 三乙胺 作用下， 以 水 、 乙腈 为溶剂， 反应 96.0h， 生成 (R)-N-(benzyloxycarbonyl)-2-(2'-propenyl)proline
  参考文献：
  名称：

  Synthesis, conformational properties, and antibody recognition of peptides containing .beta.-turn mimetics based on .alpha.-alkylproline derivatives

  摘要：

  Peptide recognition by monoclonal antibodies may provide a useful model for drug development, in particular to test the effects of conformational restriction on ligand binding. We have tested the influence of novel peptide mimetics upon conformation and binding affinity for the case of monoclonal antibodies raised to a peptide antigen which displays a preference for a beta-turn conformation in aqueous solution. Two monoclonals were isolated that recognized the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala specifically at the beta-turn formed by Tyr-Pro-Tyr-Asp. Peptide analogues were then synthesized containing mimetics designed to stabilize this conformation. One, analogue (3), contained a spirocyclic gamma-lactam bridge between the alpha-position of proline-2 and the N atom of tyrosine-3, while another (2) contained (S)-alpha-methylproline at position 2. NMR spectroscopy and molecular modeling suggest that both analogues adopt reverse-turn conformations stabilized relative to that in the native sequence. For the (S)-alpha-methylproline analogue binding to both monoclonal antibodies was substantially improved, compared with the native antigen, whereas the gamma-lactam analogue (3) was not recognized by either antibody. Quantitative equilibrium ultrafiltration binding assays showed that the affinities of the (S)-alpha-methylproline analogue (2) for the two antibodies were improved over those measured with the native antigen by -2.3 and -0.65 kcal/mol. The origins of these free energy differences cannot be explained wholly on the basis of presumed extra hydrophobic contacts between the new methyl substituent and the antigen binding sites. We propose that the increased conformational stability of the analogue plays a decisive role, implying that the reverse turn detected in the native antigen, possibly a type-I turn, is important for recognition by the two antibodies.

  DOI：

  10.1021/jm00110a005

文献信息

• Design and Synthesis of Helical N-Terminal l-Prolyl Oligopeptides Possessing Hydrocarbon Stapling
  作者：Atsushi Ueda、Mei Higuchi、Kazuki Sato、Tomohiro Umeno、Masakazu Tanaka

  DOI：10.3390/molecules25204667

  日期：——

  We designed and synthesized helical short oligopeptides with an l-proline on the N-terminus and hydrocarbon stapling on the side chain. Side-chain stapling is a frequently used method for the development of biologically active peptides. Side-chain stapling can stabilize the secondary structures of peptides, and, therefore, stapled peptides may be applicable to peptide-based organocatalysts. Olefin-tethered

  我们设计并合成了N端有L-脯氨酸、侧链有碳氢化合物的螺旋短寡肽。侧链装订是开发生物活性肽的常用方法。侧链钉合可以稳定肽的二级结构，因此钉合肽可能适用于基于肽的有机催化剂。烯烃连接的顺式-4-羟基-L-脯氨酸1和L-丝氨酸2和8，以及(R)-α-烯丙基-脯氨酸18被用作交联基序并掺入螺旋肽序列中。分别观察到肽 3 和 11（i,i+1 系列）的闭环复分解反应具有 Z-和 E-选择性，而 19（i,i+ 系列）的闭环复分解反应没有观察到 E/Z-选择性。 3 系列）。装订肽 B' 催化 1-甲基吲哚与 α,β-不饱和醛的迈克尔加成反应，比未装订肽 B 快七倍。此外，即使在较低的催化剂负载量（5 mol %) 和较低的温度 (0 °C)。钉合肽B'的圆二色光谱显示出比未钉合肽B更高强度的右旋螺旋。这些结果表明侧链钉合的引入有利于增强短寡肽催化剂的催化活性。
• PEPTIDE DERIVATIVES
  申请人：——

  公开号：US20020103335A1

  公开（公告）日：2002-08-01

  The invention concerns pharmaceutically useful peptide derivatives of the formula (I), P-AA I -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -AA 7 -AA 8 -Q, in which P, AA 1, AA 2, AA 3 , AA 4, AA 5, AA 6, AA 7, AA 8, and Q have the various meanings defined herein and their pharmaceutically accentable salts, and pharmaceutical compositions containing them. The novel peptide derivatives are of value in treating MHC class II dependent T-cell mediated autoimmune or inflammatory diseases, such as rheumatoid arthritis. The invention further concerns processes for the manufacture of the novel peptide derivatives and the use of the compounds in medical treatment.

  该发明涉及公式(I)的药用肽衍生物，P-AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -AA 7 -AA 8 -Q，其中P，AA 1，AA 2，AA 3，AA 4，AA 5，AA 6，AA 7，AA 8和Q具有本文中定义的各种含义及其药用盐，以及含有它们的药物组合物。这些新型肽衍生物对于治疗MHC II类依赖性T细胞介导的自身免疫或炎症性疾病，如类风湿性关节炎，具有价值。该发明还涉及新型肽衍生物的制造过程以及化合物在医学治疗中的使用。
• Novel Bicyclic Lactams as XaaPro Type VI β Turn Mimics:  Design, Synthesis, and Evaluation
  作者：Kyonghee Kim、Jean-philippe Dumas、Juris P. Germanas

  DOI：10.1021/jo960012w

  日期：1996.1.1

  The design, enantioselective synthesis, and structural characterization of novel bicyclic lactams as peptide mimics of the type VI beta turn is described. The mimics duplicate the conformation of the backbone and disposition of the side-chain atoms of the central two residues of the turn. The Gly L-Pro mimic, lactam 6, was prepared in good overall yield starting from (S)-2-(2'-propenyl)proline. (1)H

  描述了新型双环内酰胺作为VIβ型转弯肽模拟物的设计，对映选择性合成和结构表征。该模拟物复制了骨架的构型和该匝的中心两个残基的侧链原子的布置。从（S）-2-（2'-丙烯基）脯氨酸开始，以良好的总收率制备了Gly L-Pro模拟物内酰胺6。（1）1 H NMR光谱确定了内酰胺六元环的取代基的相对立体化学和构象特征；X射线晶体学分析证实了构象和立体化学分配。对内酰胺6的晶体结构的检查表明，中央酰胺键明显扭曲出平面度。酰胺键的扭曲归因于在两个环的交界处存在sp（2）-杂化氮原子而导致的角度应变。内酰胺6的N，N-二甲基甲am衍生物的烯醇化物与苄基溴的烷基化选择性地提供了甲am11，其为VI-turn构型的L-Phe L-Pro二肽的模拟物。高度合成的模拟肽（例如11）的有效合成途径将在肽结构功能研究中被证明非常有用。
• Design and synthesis of a novel peptide β-turn mimetic
  作者：Mark G. Hinds、Nigel G. J. Richards、John A. Robinson

  DOI：10.1039/c39880001447

  日期：——

  The stereospecific synthesis of the novel spirocyclic unit (7), and its use in the construction by solid phase methods, of a conformationally locked analogue of the immunodominant nonapeptide (1) is described.

  描述了新型螺环单元（7）的立体定向合成及其在固相方法中的结构，该结构为免疫显性九肽（1）的构象锁定类似物。
• Synthesis of a Type-VI?-Turn Peptide Mimetic and Its Incorporation into a High-Affinity Somatostatin Receptor Ligand
  作者：Dieter Gramberg、Christoph Weber、Reto Beeli、Janice Inglis、Christian Bruns、John A. Robinson

  DOI：10.1002/hlca.19950780614

  日期：1995.9.20

  synthesis of a cis-Phe-Pro dipeptide mimetic is described, which adopts a type-VIβ-turn conformation. In this mimetic, the α-positions of Phe and Pro are joined by a CH2CH2 bridge, thereby forming a fused bicyclic system, and fixing a geometry similar to that seen in cis-Phe-Pro units in protein crystal structures. The dipeptide mimetic 20 was synthesized in optically pure form starting from (R)-α-allylproline

  描述了顺式-Phe-Pro二肽模拟物的合成，其采用VIβ-转角构象。在该模拟物中，Phe和Pro的α-位置通过CH 2 CH 2桥连接，从而形成稠合的双环系统，并固定了类似于在蛋白质晶体结构中的顺式-Phe-Pro单元中所见的几何形状。从（R）-α-烯丙基脯氨酸（6 ;方案1，3和4开始）以光学纯净的形式合成二肽模拟物20。），游离羧酸和Fmoc保护的N末端，从而允许使用标准固相方法将其掺入线性和环状肽中。将模拟物20并入环状生长抑素类似物环（-Phe ＝ Pro-Phe-D-Trp-Lys-Thr-），其中Phe ＝ Pro代表模拟物。该类似物显示出高亲和力（p IC 508.6）用于大鼠脑皮质膜上的生长抑素受体。根据水溶液中的NMR研究，可使用受限的动态模拟退火推论出该类似物可能的低能构象。发现的构象，包括在D-Trp-Lys处扭曲的II'型拐点，类似于在其他地方推导的环（-Phe-P