Cbz-Pro-Pro-OH | 7360-23-8

• 物质功能分类: 医药中间体 - 杂环化合物
• 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: Cbz-Pro-Pro-OH
• 英文别名: (S)-1-((S)-1-(benzyloxycarbonyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carboxylic acid；N-benzyloxycarbonyl-(2S)-prolyl-(2S)-proline；benzyloxycarbonylprolylproline；Z-Pro-Pro-OH；Z-Pro-Pro；CbzProProOH；(2S)-1-[(2S)-1-phenylmethoxycarbonylpyrrolidine-2-carbonyl]pyrrolidine-2-carboxylic acid
• CAS: 7360-23-8
• 化学式: C₁₈H₂₂N₂O₅
• 分子量: 346.383
• InChiKey: GEAZFVPWHCGNLW-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  室温、密封、干燥

制备方法与用途

Z-Pro-Pro是一种肽。

反应信息

• 作为反应物：
  描述：

  Cbz-Pro-Pro-OH 在 N-甲基吗啉 、 盐酸 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， -5.0~20.0 ℃ 、413.7 kPa 条件下， 生成 GLYX13抑制剂
  参考文献：
  名称：

  PROCESS AND INTERMEDIATES FOR SYNTHESIS OF PEPTIDE COMPOUNDS

  摘要：

  披露了一种用于制备双吡咯啉肽类化合物（例如rapastinel）的新工艺和中间体。该工艺具有工业可扩展性和经济性，并使用较少毒性试剂和/或溶剂。此外，该工艺可用于制备纯度更高的肽类化合物。

  公开号：

  US20190031715A1
• 作为产物：
  描述：

  (S)-benzyl 2-((S)-2-(methoxycarbonyl)pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以86%的产率得到Cbz-Pro-Pro-OH
  参考文献：
  名称：

  PROCESS AND INTERMEDIATES FOR SYNTHESIS OF PEPTIDE COMPOUNDS

  摘要：

  披露了一种用于制备双吡咯啉肽类化合物（例如rapastinel）的新工艺和中间体。该工艺具有工业可扩展性和经济性，并使用较少毒性试剂和/或溶剂。此外，该工艺可用于制备纯度更高的肽类化合物。

  公开号：

  US20190031715A1

文献信息

• [EN] PROCESSES FOR SYNTHESIS OF DIPYRROLIDINE PEPTIDE COMPOUNDS<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE COMPOSÉS PEPTIDIQUES DE DIPYRROLIDINE
  申请人：NAUREX INC

  公开号：WO2017136348A1

  公开（公告）日：2017-08-10

  Disclosed is a new process for preparing dipyrrolidine peptide compounds such as, for example, GLYX-13. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.

  披露了一种新的制备二吡咯啉肽化合物的过程，例如GLYX-13。该过程具有工业可扩展性和成本效益，并且使用较少有毒试剂和/或溶剂。此外，该过程可用于制备纯度提高的肽化合物。
• INHIBITORS OF COLLAGEN PROLYL 4-HYDROXYLASE
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：US20160280701A1

  公开（公告）日：2016-09-29

  Biheteroaryl dicarboxylates and esters, and salts thereof which are useful as modulators of CP4H activity and more particularly as inhibitors of CP4H. Compounds of formula: and salts thereof where: X is S, O, NH, or NR, where R is an alkyl group having 1-3 carbon atoms; R 1 and R 2 independently are —OR 7 , or —NHSO 2 R 8 , where R 7 is selected from: hydrogen, alkyl, alkenyl, alkoxyalkyl, —R′—CO—R″, —R′—CO—O—R″, —CO—R″, —R′—O—CO—R″, —R′—CO—NR″, —CO—NR″, or —R′—O—CO—NR″, and R 8 is selected from hydrogen, alkyl, aryl, arylalkyl; R 3 , R 4 and R 6 independently are hydrogen, alkyl, alkoxy, alkenyl, alkenoxy, halo alkyl, haloalkenyl, halogen, hydroxyl, hydroxyalkyl, hydroxyalkenyl, aryl, aryloxy, arylalkyl or arylalkyloxy; R 5 is hydrogen, halogen, alkyl having 1-3 carbon atoms, or alkoxy having 1-3 carbon atoms; —R′— is a divalent straight chain or branched alkylene, and —R″ is an alkyl, alkenyl, arylalkyl, or aryl group. Methods for inhibition of CP4H in vivo and in vitro.

  Biheteroaryl二羧酸酯和酯，以及它们的盐，可用作CP4H活性的调节剂，更具体地作为CP4H的抑制剂。化合物的结构式:及其盐，其中:X为S、O、NH或NR，其中R为具有1-3个碳原子的烷基基团；R1和R2独立地为—OR7，或—NHSO2R8，其中R7选自：氢、烷基、烯基、烷氧基烷基、—R′—CO—R″、—R′—CO—O—R″、—CO—R″、—R′—O—CO—R″、—R′—CO—NR″、—CO—NR″或—R′—O—CO—NR″，而R8选自氢、烷基、芳基、芳基烷基；R3、R4和R6独立地为氢、烷基、烷氧基、烯基、烯氧基、卤代烷基、卤代烯基、卤素、羟基、羟基烷基、羟基烯基、芳基、芳氧基、芳基烷基或芳基烷氧基；R5为氢、卤素、具有1-3个碳原子的烷基，或具有1-3个碳原子的烷氧基；—R′—为二价的直链或支链烷基，而—R″为烷基、烯基、芳基烷基或芳基。用于体内和体外抑制CP4H的方法。
• Studies of Bitter Peptides from Casein Hydrolyzate. VII. Bitterness of the retro-BPIa (Val–Ile–Phe–Pro–Pro–Gly–Arg) and Its Fragments
  作者：Toshiaki Shigenaga、Ken Otagiri、Hidenori Kanehisa、Hideo Okai

  DOI：10.1246/bcsj.57.103

  日期：1984.1

  To explain the bitter taste exhibited by BPIa (Arg–Gly–Pro–Pro–Phe–Ile–Val) which was isolated from casein hydrolyzate, we have proposed the following requirement: its characteristic spatial structure: the basic moiety in the N-terminal and the hydrophobic moiety in the C-terminal were affected to each other by prolylprolyl residue, is necessary for the bitterness to be exhibited. As for BPIc (Val–Tyr–Pro–Phe–Pro–Pro–Gly–Ile–Asn-His), which is the other fraction, although it exhibited as strong and bitter a taste as BPIa, the basic moiety of BPIc is located in the C-terminal and its hydrophobic moiety is located in the N-terminal. The authors synthesized retro-BPIa with the reverse peptide sequence and its fragments. The retro-BPIa exhibited as strong and bitter a taste as BPIa. However, the bitterness of the fragments of retro-BPIa was far weaker than that of retro-BPIa.

  为了说明从酪蛋白水解物中分离出的BPIa（Arg–Gly–Pro–Pro–Phe–Ile–Val）所表现出的苦味，我们提出了以下要求：其特征空间结构，即N末端的基本部分与C末端的疏水部分通过脯氨酸残基相互影响，是表现苦味所必需的。至于另一种成分BPIc（Val–Tyr–Pro–Phe–Pro–Pro–Gly–Ile–Asn-His），虽然它表现出的味道与BPIa一样强烈而苦涩，但BPIc的基本部分位于C末端，疏水部分位于N末端。作者合成了逆BPIa，其肽序列相反及其片段。逆BPIa表现出的苦味同样强烈，但逆BPIa片段的苦味远弱于逆BPIa。
• Solid-state conformation of diastereomeric -Pro-Pro-(Aib)4 sequences
  作者：Makoto Oba、Yosuke Demizu、Nanako Yamagata、Yukiko Sato、Mitsunobu Doi、Masakazu Tanaka、Hiroshi Suemune、Haruhiro Okuda、Masaaki Kurihara

  DOI：10.1016/j.tet.2010.02.003

  日期：2010.3

  a=10.470 Å, b=10.953 Å, c=32.405 Å, Z=4, R1=0.040, and Rw=0.046. In the asymmetric unit of 1, the homochiral l-Pro1-l-Pro2 adopts a polyproline II structure, which induces a left-handed (M) 310-helical structure in the following -(Aib)4- sequence. The preferred conformation of diastereomeric 2, which contains heterochiral d-Pro1-l-Pro2 segments, was similar to that of 1 with differences at the N-terminal

  2非对映异构-Pro-亲（AIB）的晶体结构4 -序列，CBZ-升-Pro-升-Pro-（AIB）4 -OMe（1）和CBZ- d -Pro-升-Pro-（Aib取代）4- OMe（2），已经通过X射线晶体学分析确定。这两种化合物的晶体通过下列参数表征：（1）单斜晶，P 2 1，一个= 10.543埃，b = 8.103埃，c ^ = 22.642埃，β = 97.679，Ž = 2，- [R 1 = 0.104，和R w = 0.327；（2）正交晶，P 2 1 2 1 2 1，a＝ 10.470，b＝ 10.953，c＝ 32.405，Z＝ 4，R 1＝ 0.040，R w＝ 0.046。在的不对称单元1中，纯手性升-Pro 1 -升-Pro 2采用聚脯氨酸II结构，其诱导左手（中号）3 10在下文中螺旋结构- （AIB）4- 顺序。非对映体的优选构象2，其含有异向d -Pro 1 -升-Pro
• Structures, Sensory Activity, and Dose/Response Functions of 2,5-Diketopiperazines in Roasted Cocoa Nibs (<i>Theobroma cacao</i>)
  作者：Timo Stark、Thomas Hofmann

  DOI：10.1021/jf051313m

  日期：2005.9.1

  The taste compounds inducing the blood-like, metallic bitter taste sensation reported recently for a dichloromethane extract prepared from roasted cocoa nibs were identified as a series of 25 diketopiperazines by means of HPLC degustation, LC-MS/MS, and independent synthesis. Among these 25 compounds, 13 cis-configured diketopiperazines, namely, CYCIO(L-IIe-L-Phe), CYCIO(L-Val-L-Leu), CYCIO(L-Pro-L-Pro), CYCIO(L-IIe-L-Pro), CYCIO(L-Val-L-Tyr), CYCIO(L-Ala-L-Tyr), CYCIO(L-Phe-L-Ser), CYCIO(L-Ala-L-IIe), CYCIO(L-LeU-L-Phe), cyclo(L-Pro-L-Val), CYCIO(L-Pro-L-Thr), CYCIO(L-PrO-L-Tyr), and CYCIO(L-Val-L-Val) were identified for the first time in cocoa. In addition, the taste recognition thresholds for the metallic as well as the bitter taste of the diketopiperazines were determined, and after quantitative analysis by using two diastereomeric diketopiperazines as the internal standards, the sensory impact of the diketopiperazines was evaluated on the basis of their close-over-threshold (DoT) factors calculated as the ratio of the concentration and the threshold concentration of a compound. These data revealed DoT factors above 1.0 exclusively for cis-cyclo(L-Pro-L-Val), cis-cyclo(L-Val-L-Leu), cis-cyclo(L-Ala-L-IIe), cis-cyclo(L-Ala-L-Leu), and cis-cyclo(L-IIe-L-Pro), whereas all of the other diketopiperazines were present below their individual bitter taste threshold concentrations and should therefore not contribute to the cocoa taste. Because the DoT factors do not consider the nonlinear relationship between the concentration and gustatory response of an individual compound, we, for the first time, report on the recording of dose/response functions describing the human bitter taste perception of diketopiperazines more precisely.