Fmoc-Ala-Cys(ψMe,Me-pro)-OH | 158531-43-2

• 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: Fmoc-Ala-Cys(ψMe,Me-pro)-OH
• 英文别名: (R)-3-((((9H-Fluoren-9-yl)methoxy)carbonyl)-L-alanyl)-2,2-dimethylthiazolidine-4-carboxylic acid；(4R)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoyl]-2,2-dimethyl-1,3-thiazolidine-4-carboxylic acid
• CAS: 158531-43-2
• 化学式: C₂₄H₂₆N₂O₅S
• 分子量: 454.547
• InChiKey: UWQSXNJYTWZIQD-XOBRGWDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Fmoc-Ala-Cys(ψMe,Me-pro)-OH 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (4R)-3-[(2S)-2-acetamidopropanoyl]-N,2,2-trimethyl-1,3-thiazolidine-4-carboxamide
  参考文献：
  名称：

  Pseudo-Prolines as a Molecular Hinge:  Reversible Induction of cis Amide Bonds into Peptide Backbones

  摘要：

  Serine, threonine-derived (4S)-oxazolidine-4-carboxylic acid, and cysteine-derived (4R)-thiazolidinecarboxylic acid, denoted pseudo-proline (Xaa[Psi(R1,R2)pro]), serve as structure disrupting, solubilizing building blocks in peptide synthesis. Variation of the 2-C substituents within the heterocyclic system results in different physicochemical and conformational properties. NMR studies of a series of pseudo-proline (Psi Pro)-containing peptides reveal a pronounced effect of the 2-C substituents upon the cis to trans ratio of the adjacent amide bond in solution. 2-C unsubstituted systems show a preference similar to that of the proline residue for the trans form, whereas 2,2-dimethylated derivatives adopt the cis amide conformation in high content. For 2-monosubstituted Psi Pro, the cis-trans distribution depends on the 2-C chirality. For the 2-(S)-diastereoisomer, both forms are similarly populated in solution, whereas the 2-(R)-epimer adopts preferentially the trans form. The results are supported by conformational energy calculations and suggest that, by tailoring the degree of substitution, pseudo-prolines may serve as a temporary proline mimetic or as a hinge in peptide backbones.

  DOI：

  10.1021/ja962780a
• 作为产物：
  描述：

  N-(9-fluorenylmethoxycarbonyl)-L-alanyl fluoride 、 (4R)-2,2-二甲基-4-噻唑烷甲酸 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以62%的产率得到Fmoc-Ala-Cys(ψMe,Me-pro)-OH
  参考文献：
  名称：

  伪脯氨酸作为肽合成中的增溶、结构破坏保护技术

  摘要：

  丝氨酸、苏氨酸和半胱氨酸衍生的环状结构单元（伪脯氨酸，ΨPro）作为 Ser、Thr 和 Cys 的可逆保护基团，并被证明是克服肽化学领域一些内在问题的通用工具。肽序列中 ΨPro 的存在导致被认为是链延长过程中分子间聚集来源的 β-折叠结构的破坏，从而增加了肽组装中的溶剂化和偶联动力学。由于它们易于合成，并且通过在恶唑烷/噻唑烷环系统的 C-2 位置引入修饰而导致化学稳定性的可变性，因此这种保护技术适用于肽合成中的所有常见策略。

  DOI：

  10.1021/ja961509q

文献信息

• Synthesis of Cyclogossine B Using a Traceless Pseudoproline Turn-Inducer
  作者：Michelle S. Y. Wong、Katrina A. Jolliffe

  DOI：10.1071/ch09643

  日期：——

  The first synthesis of the cyclic octapeptide, cyclogossine B, has been achieved, confirming the reported structure of this natural product. Cyclization of a linear precursor containing a cysteine-derived thiazolidine as a traceless turn-inducer occurred in significantly higher yields than cyclization of the analogous alanine-containing precursor under identical conditions. Deprotection of the thiazolidine followed by desulfurization provided cyclogossine B in good overall yield, indicating that cysteine-derived pseudoprolines can be effectively used as traceless turn-inducers to facilitate the cyclization of small peptides.

  首次合成了环状八肽环高辛 B，证实了已报道的这种天然产物的结构。在相同的条件下，含有半胱氨酸衍生的噻唑烷作为无痕转向诱导剂的线性前体的环化产率明显高于含有类似丙氨酸的前体的环化产率。先对噻唑烷进行脱保护，然后再进行脱硫处理，就可以得到总产率很高的环高辛 B，这表明半胱氨酸衍生的假脯氨酸可以有效地用作无踪转向诱导剂，促进小肽的环化。
• Pseudo-Prolines as a Molecular Hinge:  Reversible Induction of <i>cis</i> Amide Bonds into Peptide Backbones
  作者：Pascal Dumy、Michael Keller、Declan E. Ryan、Barbara Rohwedder、Torsten Wöhr、Manfred Mutter

  DOI：10.1021/ja962780a

  日期：1997.2.1

  Serine, threonine-derived (4S)-oxazolidine-4-carboxylic acid, and cysteine-derived (4R)-thiazolidinecarboxylic acid, denoted pseudo-proline (Xaa[Psi(R1,R2)pro]), serve as structure disrupting, solubilizing building blocks in peptide synthesis. Variation of the 2-C substituents within the heterocyclic system results in different physicochemical and conformational properties. NMR studies of a series of pseudo-proline (Psi Pro)-containing peptides reveal a pronounced effect of the 2-C substituents upon the cis to trans ratio of the adjacent amide bond in solution. 2-C unsubstituted systems show a preference similar to that of the proline residue for the trans form, whereas 2,2-dimethylated derivatives adopt the cis amide conformation in high content. For 2-monosubstituted Psi Pro, the cis-trans distribution depends on the 2-C chirality. For the 2-(S)-diastereoisomer, both forms are similarly populated in solution, whereas the 2-(R)-epimer adopts preferentially the trans form. The results are supported by conformational energy calculations and suggest that, by tailoring the degree of substitution, pseudo-prolines may serve as a temporary proline mimetic or as a hinge in peptide backbones.
• Pseudo-Prolines as a Solubilizing, Structure-Disrupting Protection Technique in Peptide Synthesis
  作者：Torsten Wöhr、Franck Wahl、Adel Nefzi、Barbara Rohwedder、Tatsunori Sato、Xicheng Sun、Manfred Mutter

  DOI：10.1021/ja961509q

  日期：1996.1.1

  in the C-2 position of the oxazolidine/thiazolidine ring system, this protection technique is adaptable to all common strategies in peptide synthesis. We describe new types of ΨPro building blocks suitable for standard Fmoc/tBu-based solid phase peptide synthesis, convergent strategies, and chemoselective ligation techniques as well as their use as a structure-disrupting, solubilizing protection technique

  丝氨酸、苏氨酸和半胱氨酸衍生的环状结构单元（伪脯氨酸，ΨPro）作为 Ser、Thr 和 Cys 的可逆保护基团，并被证明是克服肽化学领域一些内在问题的通用工具。肽序列中 ΨPro 的存在导致被认为是链延长过程中分子间聚集来源的 β-折叠结构的破坏，从而增加了肽组装中的溶剂化和偶联动力学。由于它们易于合成，并且通过在恶唑烷/噻唑烷环系统的 C-2 位置引入修饰而导致化学稳定性的可变性，因此这种保护技术适用于肽合成中的所有常见策略。