3α-hydroxypyrrolo[2,3-b]indolylglycine methyl ester

• 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: 3α-hydroxypyrrolo[2,3-b]indolylglycine methyl ester
• 英文别名: [syn-cys]-H-Hpi-Gly-OMe；H-Hpi-Gly-OMe；methyl 2-[[(2S,3aR,8bR)-8b-hydroxy-2,3,3a,4-tetrahydro-1H-pyrrolo[2,3-b]indole-2-carbonyl]amino]acetate
• 化学式: C₁₄H₁₇N₃O₄
• 分子量: 291.307
• InChiKey: ANUZZHITYAVJGY-LEWSCRJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  99.7
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3α-hydroxypyrrolo[2,3-b]indolylglycine methyl ester 、 Fmoc-L-异亮氨酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 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 18.0h， 以40%的产率得到[syn-cis]-Fmoc-Ile-Hpi-Gly-OMe
  参考文献：
  名称：

  环内Savige-Fontana反应：将一类单环肽一步转化为另一类双环肽。

  摘要：

  环化和交联策略对于合成环状和双环肽很重要。这些大内酰胺由于与线性类似物相比具有增强的生物活性而引起人们的极大兴趣。在本文中，我们描述了含有Hpi毒基团的环状肽的合成，让人联想到phakellistatins和omphalotins。然后提出了这种肽的首次环内交联：使用纯TFA催化Savige-Fontana色氨酸的亚硫酰化，将含Hpi的肽转化为双环酰胺毒素类似物。这样，该方法学代表了用于交联肽的有效环化方法，并揭示了两种不同类别的肽天然产物之间迄今未实现的关系。这一发现增加了用于文库生成的潜在化学空间的程度。

  DOI：

  10.1002/chem.200701088
• 作为产物：
  描述：

  methyl 2-[(2S)-3-(1H-indol-3-yl)-2-[(triphenylmethyl)amino]propanamido]acetate 在 二甲基二环氧乙烷 、 六氟异丙醇 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 0.5h， 以40%的产率得到3α-hydroxypyrrolo[2,3-b]indolylglycine methyl ester
  参考文献：
  名称：

  High Yielding Synthesis of 3a-Hydroxypyrrolo[2,3-b]indoline Dipeptide Methyl Esters:  Synthons for Expedient Introduction of the Hydroxypyrroloindoline Moiety into Larger Peptide-Based Natural Products and for the Creation of Tryptathionine Bridges

  摘要：

  This work describes a rapid and high yielding oxidation of 14 tryptophanylated amino acid methyl esters to the corresponding 3 alpha-hydroxypyrrolo[2,3-b]indoline (Hpi) amino acids with generally facile separation of syn-cis and anti-cis diastereomers. Structural X-ray diffraction data are presented for both diastereomers of Tr-Hpi-Gly-OMe, which allow for a putative assignment of the other 13 pairs of diastereomers reported herein, based on correlations with H-1 NMR chemical shifts. Selective and high yielding deprotection at either the N or C terminus is described, allowing the Hpi motif to be introduced efficiently into potential targets with minimal protecting group manipulation. Two tripeptides containing Hpi and cysteine were prepared and treated with acid in the Savige-Fontana reaction to produce a cyclic tryptathionine linkage, characteristic of both amatoxins and phallotoxins.

  DOI：

  10.1021/jo051105t

文献信息

• High Yielding Synthesis of 3<i>a</i>-Hydroxypyrrolo[2,3-<i>b</i>]indoline Dipeptide Methyl Esters:  Synthons for Expedient Introduction of the Hydroxypyrroloindoline Moiety into Larger Peptide-Based Natural Products and for the Creation of Tryptathionine Bridges
  作者：Jonathan P. May、Pierre Fournier、Jonathan Pellicelli、Brian O. Patrick、David M. Perrin

  DOI：10.1021/jo051105t

  日期：2005.10.1

  This work describes a rapid and high yielding oxidation of 14 tryptophanylated amino acid methyl esters to the corresponding 3 alpha-hydroxypyrrolo[2,3-b]indoline (Hpi) amino acids with generally facile separation of syn-cis and anti-cis diastereomers. Structural X-ray diffraction data are presented for both diastereomers of Tr-Hpi-Gly-OMe, which allow for a putative assignment of the other 13 pairs of diastereomers reported herein, based on correlations with H-1 NMR chemical shifts. Selective and high yielding deprotection at either the N or C terminus is described, allowing the Hpi motif to be introduced efficiently into potential targets with minimal protecting group manipulation. Two tripeptides containing Hpi and cysteine were prepared and treated with acid in the Savige-Fontana reaction to produce a cyclic tryptathionine linkage, characteristic of both amatoxins and phallotoxins.
• Intraannular Savige–Fontana Reaction: One-Step Conversion of One Class of Monocyclic Peptides into Another Class of Bicyclic Peptides
  作者：Jonathan P. May、David M. Perrin

  DOI：10.1002/chem.200701088

  日期：2008.4.7

  cyclic and bicyclic peptides. These macrolactams are of great interest due to their increased biological activity compared to linear analogues. Herein, we describe the synthesis of a cyclic peptide containing an Hpi toxicophore, reminiscent of phakellistatins and omphalotins. The first intraannular cross-linking of such a peptide is then presented: using neat TFA to catalyse a Savige-Fontana tryptathionylation

  环化和交联策略对于合成环状和双环肽很重要。这些大内酰胺由于与线性类似物相比具有增强的生物活性而引起人们的极大兴趣。在本文中，我们描述了含有Hpi毒基团的环状肽的合成，让人联想到phakellistatins和omphalotins。然后提出了这种肽的首次环内交联：使用纯TFA催化Savige-Fontana色氨酸的亚硫酰化，将含Hpi的肽转化为双环酰胺毒素类似物。这样，该方法学代表了用于交联肽的有效环化方法，并揭示了两种不同类别的肽天然产物之间迄今未实现的关系。这一发现增加了用于文库生成的潜在化学空间的程度。