N-carbobenzoxy-L-Phe-L-Pro-NH2 | 83871-06-1

• 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: N-carbobenzoxy-L-Phe-L-Pro-NH2
• 英文别名: Z-Phe-Pro-NH2；N-benzyloxycarbonyl-L-phenylalanyl-L-prolinamide；Z-L-Phg-Pro-NH2；Cbz-L-Phe-L-Pro-NH2；benzyl N-[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 83871-06-1
• 化学式: C₂₂H₂₅N₃O₄
• 分子量: 395.458
• InChiKey: GDTCWFSQUYMJAR-OALUTQOASA-N

物化性质

• 沸点：
  696.5±55.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-carbobenzoxy-L-Phe-L-Pro-NH2 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 12.0h， 生成 (S)-1-((S)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid amide
  参考文献：
  名称：

  缓冲条件下含色氨酸肽的串联电化学氧化叠氮/杂环化

  摘要：

  锰催化后期衍生化用于通过自由基叠氮化/杂环化级联构建叠氮取代的四唑并[1,5- a ]吲哚肽。这种电化学氧化策略可以在缓冲溶液中温和、高效、环保的条件下进行。

  DOI：

  10.1002/anie.202206308
• 作为产物：
  描述：

  1-(N-((苯基甲氧基)羰基)-L-苯丙氨酰)-L-脯氨酸 在 吡啶 、 二碳酸二叔丁酯 、 碳酸氢铵 作用下， 生成 N-carbobenzoxy-L-Phe-L-Pro-NH2
  参考文献：
  名称：

  一种一步合成膦酸肽的简便方法

  摘要：

  提出了一种新颖而有效的合成1-氨基烷基膦酸酯二芳基酯的肽基衍生物的方法。使用N-保护的氨基酸或肽的酰胺，亚磷酸三苯酯和适当的醛，通过酰胺基烷基化反应，一步一步即可获得磷酸肽。

  DOI：

  10.1016/j.tetlet.2013.07.049

文献信息

• PyOxP and PyOxB: the Oxyma-based novel family of phosphonium salts
  作者：Ramon Subirós-Funosas、Ayman El-Faham、Fernando Albericio

  DOI：10.1039/c003719b

  日期：——

  Recent studies described the great impact of a non-benzotriazolic family of coupling reagents based on ethyl 2-cyano-2-(hydroxyimino)acetate, Oxyma, as a powerful coupling methodology for peptide synthesis. Here we present the synthesis and evaluation of the derived phosphonium salts O-[(1-cyano-2-ethoxy-2-oxoethylidene)amino]-oxytri(pyrrolidin-1-yl) phosphonium hexafluorophosphate (PyOxP) and tetrafluoroborate (PyOxB). Both coupling reagents exhibited higher capacity to suppress racemization in various peptide models and enhanced solubility in DMF and DCM than benzotriazole-based reagents. In addition, the hexafluorophosphate analog PyOxP, combined excellent stability with outstanding efficiency in the assembly of demanding penta and decapeptides that include consecutive Aib residues. Cyclization models revealed the advantages of PyOxP, which rendered a higher percentage of cyclic material than other known potent phosphonium salts.

  最近的研究表明，基于 2-氰基-2-(羟基亚氨基)乙酸乙酯的非苯并三氮唑偶联试剂 Oxyma 系列作为一种强大的偶联方法对多肽合成具有重大影响。在此，我们介绍了衍生鏻盐 O-[(1-氰基-2-乙氧基-2-氧代亚乙基)氨基]-氧三(吡咯烷-1-基)鏻六氟磷酸盐（PyOxP）和四氟硼酸盐（PyOxB）的合成和评估。与苯并三唑类试剂相比，这两种偶联试剂在各种肽模型中抑制消旋化的能力更强，在 DMF 和 DCM 中的溶解度也更高。此外，六氟磷酸类似物 PyOxP 在组装包含连续 Aib 残基的高要求五肽和十肽时，兼具出色的稳定性和卓越的效率。环化模型显示了 PyOxP 的优势，与其他已知的强效鏻盐相比，PyOxP 生成的环状物质比例更高。
• Potential Thyroliberin Affinity Labels II: Chloroacetyl Substituted Phenylalanyl Prolineamides
  作者：Richard J. Goebel、Bruce L. Currie、Cyril Y. Bowers

  DOI：10.1002/jps.2600710928

  日期：1982.9

  Three analogs of thyroliberin (I) were prepared. These compounds, N-m-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIa), N-p-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIb) and N-chloroacetyl-alanyl-phenylalanyl-prolineamide (IX), were designed as potential I antagonist affinity labels. However, no significant antagonist activity was observed. Compounds VIa and IX were found to have weak agonist

  制备了三种甲状腺素（I）类似物。这些化合物Nm-氯乙酰基苯甲酰基-苯丙氨酰-脯氨酸（VIa），Np-氯乙酰基苯甲酰基-苯丙氨酰-脯氨酸（VIb）和N-氯乙酰基-苯丙酰基-苯丙氨酰-脯氨酸（IX）被设计为潜在的I拮抗剂亲和标记。但是，没有观察到明显的拮抗剂活性。发现化合物VIa和IX具有弱的激动剂活性。然而，发现环（Phe-Pro）是I代谢产物的类似物，环（His-Pro）具有明显的I拮抗剂活性，但没有激动剂活性。
• Inhibitors of Tripeptidyl Peptidase II. 3. Derivation of Butabindide by Successive Structure Optimizations Leading to a Potential General Approach to Designing Exopeptidase Inhibitors
  作者：C. Robin Ganellin、Paul B. Bishop、Ramesh B. Bambal、Suzanne M. T. Chan、Bertrand Leblond、Andrew N. J. Moore、Lihua Zhao、Pierre Bourgeat、Christiane Rose、Froylan Vargas、Jean-Charles Schwartz

  DOI：10.1021/jm0500830

  日期：2005.11.1

  The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO(3)H)-Met-OH + GlyTrp-Met-Asp-Phe-NH(2). Starting from Val-Pro-NHBu, a dipeptide of submicromolar affinity that had previously been generated to serve as a lead, successive optimization at P3, P1, and then P2 gave Abu-Pro-NHBu (18, K(i) = 80 nM). Further transformation (by making a benzologue) gave the indoline analogue, butabindide (33) as a reversible inhibitor having nanomolar affinity (Ki = 7 nM). Retrospective analysis suggested the possibility of a general approach to designing exopeptidase inhibitors starting from the structure of the first hydrolysis product. Application of this approach to CCK-8 led to Abu-Phe-NHBu (37), but this only had K(i) = 9.4 mu M. Molecular modeling, to determine the minimum energy conformations and explain the 1000-fold better affinity of butabindide, indicated that 37 cannot access the likely active conformation of butabindide.
• Enzymatic synthesis of activated esters and their subsequent use in enzyme-based peptide synthesis
  作者：Timo Nuijens、Claudia Cusan、Annette C.H.M. Schepers、John A.W. Kruijtzer、Dirk T.S. Rijkers、Rob M.J. Liskamp、Peter J.L.M. Quaedflieg

  DOI：10.1016/j.molcatb.2011.03.012

  日期：2011.8

  Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides. However, there are still some limitations when challenging peptides, e.g. containing sterically demanding acyl donors, non-proteinogenic amino acids or proline residues, are to be synthesized. To remedy these limitations, special ester moieties have been used that are specifically recognized by the enzyme, e.g. guanidinophenyl, carboxamidomethyl (Cam) or trifluoroethyl (Tfe) esters, which, unfortunately, are notoriously difficult to synthesize chemically. Herein, we demonstrate that Cam and Tfe esters are very useful for Alcalase-CLEA mediated peptide synthesis using sterically demanding and non-proteinogenic acyl donors as well as poor nucleophiles, and combinations thereof. Furthermore, these esters can be efficiently synthesized by using the lipase Cal-B or Alcalase-CLEA. Finally, it is shown that the ester synthesis by Cal-B and subsequent peptide synthesis by Alcalase-CLEA can be performed simultaneously using a two-enzyme-one-pot approach with glycolamide or 2,2,2-trifluoroethanol as additive. (C) 2011 Elsevier B.V. All rights reserved.
• Peptide Coupling in the Presence of Highly Hindered Tertiary Amines
  作者：Louis A. Carpino、Dumitru Ionescu、Ayman El-Faham

  DOI：10.1021/jo950912x

  日期：1996.1.1

  Previously, 2,4,6-trimethylpyridine (collidine), due to steric shielding around the N-atom, was found to be an efficient base for effecting peptide segment coupling via azabenzotriazole-based onium-style coupling reagents. A number of even more highly hindered bases, including 2,3,5,6-tetramethylpyridine , 2, 6-di-tert-butyl-4-(dimethylamino)pyridine, triisopropylamine, and N-tert-butylmorpholine, have been compared with collidine in such reactions. Some of the newer bases showed advantages in terms of convenience in handling and maintenance of configuration during segment coupling processes, although dramatic differences based on steric effects were not observed. On the basis of results with a number of test peptides and many base-coupling reagent combinations, it was noted that most efficient results are obtained if 1 equiv of HOAt is present as an additive during the coupling process. For rapid activation of onium-style coupling reagents during stepwise solid-phase coupling reactions, the stronger base 2,6-di-tert-butyl-4-(dimethylamino)pyridine was more effective than collidine.