Fmoc-cis-2-amino-1-cyclopentanecarboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-cis-2-amino-1-cyclopentanecarboxylic acid
• 英文别名: (±)-cis-2-(9-fluorenylmethyloxycarbonyl)aminocyclopentanecarboxylic acid；(±)-cis-2-(FMOC-amino)cyclopentane-1-carboxylic acid；cis-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)cyclopentanecarboxylic acid；(1S,2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)cyclopentane-1-carboxylic acid
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: KTLDVIJVCPIJCM-PKOBYXMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Fmoc-L-亮氨酸 、 Fmoc-cis-2-amino-1-cyclopentanecarboxylic acid 在 N,N'-二异丙基碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 24.5h， 生成 (1S,7R)-4S-isobutyl-2,5-diazabicyclo[5.3.0]decane-3,6-dione
  参考文献：
  名称：

  Solid-phase synthesis of 6,7-cycloalkane-fused 1,4-diazepane-2,5-diones via a cyclization/release strategy

  摘要：

  A solid-phase synthesis procedure for the parallel preparation of 6,7-cycloalkane-fused 1,4-diazepane-2,5-diones is described. The methodology applies alpha- and alicyclic beta-amino acid building blocks to construct the seven-membered heterocyclic core, while alcohols are used for further skeletal decoration. The use of a cyclization/release strategy permits the isolation of the target cyclic alpha,beta-dipeptides in good crude purities and generally moderate to good yields. A 26-membered model library is reported and NMR spectroscopical data are used to describe the overall conformational behaviour of the obtained homodiketopiperazines. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.11.023
• 作为产物：
  描述：

  (1S,5R)-6-hydroxymethyl-6-azabicyclo[3.2.0]heptan-7-one 在 盐酸 、 ammonium hydroxide 、 水 、 potassium hydrogencarbonate 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 120.0h， 生成 Fmoc-cis-2-amino-1-cyclopentanecarboxylic acid
  参考文献：
  名称：

  Hairpin Folding Behavior of Mixed α/β-Peptides in Aqueous Solution

  摘要：

  The invention of new strategies for the design of protein-mimetic oligomers that manifest the folding encoded in natural amino acid sequences is a significant challenge. In contrast to the a-helix, mimicry of protein beta-sheets is less understood. We report here the aqueous folding behavior of a prototype alpha-peptide hairpin model sequence varied at cross-strand positions by incorporation of 16 different beta-amino acid monomers. Our results provide a folding propensity scale for beta-residues in a protein beta-sheet context as well as high-resolution structures of several mixed-backbone alpha/beta-peptide hairpins in water.

  DOI：

  10.1021/ja2002346

文献信息

• Controlling the Helix Handedness of ααβ-Peptide Foldamers through Sequence Shifting
  作者：Monika Szefczyk、Ewelina Węglarz-Tomczak、Paulina Fortuna、Agnieszka Krzysztoń、Ewa Rudzińska-Szostak、Łukasz Berlicki

  DOI：10.1002/anie.201610154

  日期：2017.2.13

  Peptide foldamers containing both cis‐β‐aminocyclopentanecarboxylic acid and α‐amino acid residues combined in various sequence patterns (ααβ, αααβ, αβααβ, and ααβαααβ) were screened using CD and NMR spectroscopy for the tendency to form helices. ααβ‐Peptides were found to fold into an unprecedented and well‐defined 16/17/15/18/14/17‐helix. By extending the length of the sequence or shifting a fragment

  使用CD和NMR光谱法筛选了包含顺式-β-氨基环戊烷羧酸和α-氨基酸残基的肽折叠剂，这些残基以各种序列模式（ααβ，αααβ，αβααβ和ααβαααβ）结合在一起，以形成螺旋的趋势。发现ααβ肽折叠成史无前例且定义明确的16/17/15/18/14 / 17-螺旋。通过延长序列的长度或将序列的片段从一个ααβ肽的一个末端移动到另一个末端，可以控制溶液中存在的左手和右手螺旋种群之间的平衡。肽序列的工程改造可能会导致化合物对选定的螺旋有义性有强烈的倾向，或者对相反有义的螺旋构象有很强的混合性。
• Thrombin receptor-activating peptides (TRAPs): Investigation of bioactive conformations via structure–activity, spectroscopic, and computational studies
  作者：Marco A. Ceruso、David F. McComsey、Gregory C. Leo、Patricia Andrade-Gordon、Michael F. Addo、Robert M. Scarborough、Donna Oksenberg、Bruce E. Maryanoff

  DOI：10.1016/s0968-0896(99)00180-7

  日期：1999.11

  TRAP-5 is known to tolerate a wide variety of side chains, but we also found that the amide nitrogen at this position can be substituted by an oxygen, as in SF-psi(COO)-LLR-NH2, without diminishing activity. However, this peptide bond is sensitive to conformational changes in that SFPLR-NH2 was active, whereas SF-NMeL-LR-NH2 was not. Additionally, we found that position 3 does not tolerate rigid spacers

  凝血酶受体（PAR-1）是一种不常见的跨膜G蛋白偶联受体，它通过丝氨酸蛋白酶裂解其胞外N端而被激活，从而暴露出激动剂肽配体，并与受体本身拴在一起。包含激动剂基序的合成肽，例如人PAR-1的SFLLRN，能够引起完全的受体活化。我们通过系统引入某些构象扰动（包括α-甲基，酯psi（COO）和还原酰胺psi（CH2N）扫描），将凝血酶受体激活肽（TRAPs）的可能的生物活性构象探究到最低限度激动剂序列（SFLLR），以探测骨架构象和酰胺NH氢键的重要性。我们进行了代表性五肽的广泛构象搜索，以推导假定的生物活性结构家族。此外，我们采用1 H NMR和圆二色性（CD）通过实验表征某些五肽类似物的构象。我们的五肽类似物激活的血小板聚集提供了PAR-1激动剂活性的结构-功能相关性。PAR-1受体结合数据辅助了这种相关性，PAR-1受体结合数据确定了肽配体对凝血酶受体的亲和力，而与源自受体激活（即纯分子
• Scalable Synthesis of All Stereoisomers of 2-Aminocyclopentanecarboxylic Acid─A Toolbox for Peptide Foldamer Chemistry
  作者：Vitaly Kovalenko、Ewa Rudzińska-Szostak、Katarzyna Ślepokura、Łukasz Berlicki

  DOI：10.1021/acs.joc.3c02991

  日期：2024.4.5

  application is limited by access to the appropriate building blocks. In particular, trans- and cis-stereoisomers of 2-aminocyclopentanecarboxylic acid (ACPC) are of high interest. The scalable synthesis of all four stereoisomers of Fmoc derivatives of ACPC is presented with NMR-based analysis methods for their enantiomeric purity.

  尽管使用构象受限的 β-氨基酸构建具有明确的三维结构和可预测功能（包括生物活性）的肽已被证明是一种非常成功的策略，但其广泛应用受到适当构建模块的限制。 。特别是，2-氨基环戊烷甲酸（ACPC）的反式和顺式立体异构体备受关注。 ACPC Fmoc 衍生物的所有四种立体异构体的可扩展合成采用基于 NMR 的分析方法来测定其对映体纯度。
• Large-Scale Syntheses of FMOC-Protected Non-Proteogenic Amino Acids:  Useful Building Blocks for Combinatorial Libraries
  作者：Jeffrey M. Dener、Pascal P. Fantauzzi、Tushar A. Kshirsagar、Daphne E. Kelly、Aaron B. Wolfe

  DOI：10.1021/op010204f

  日期：2001.7.1

  Convenient and reliable large-scale procedures for the protection of various amino acids with N-(9-fluorenyimethoxycarbonyl)oxysuccinimide (FMOC-OSu) are described. Commercially available 4-aminomethylbenzoic acid and trans-4-(aminomethyl)cyclohexanecarboxylic acid were converted into their corresponding FMOC-derivatives in excellent yields without the need for an extractive workup. In addition, FMOC-cis-beta -amino acids were also prepared, employing a [2 + 2]-cycloaddition strategy between a cyclic olefin and N-chlorosulfonyl isocyanate (CSI). The resulting N-chlorosulfonyl fl-lactams were reduced to the parent beta -lactams with sodium sulfite and then converted to the cis-fi-amino acid hydrochlorides by exposure to aqueous hydrochloric acid. The resulting cis-fi-amino acids were converted to their FMOC-derivatives under conditions similar to those developed for the commercially available amino acids. Differences in the conditions employed between these beta -amino acids and the commercial derivatives were observed, primarily in the nature of the base required for the reaction. A possible rationale for the differences in behavior is described. These FMOC-amino acid derivatives are valuable intermediates for the solid-phase synthesis of combinatorial libraries.