methyl (2S,3R)-2-[[(2S,3aS,8bR)-8b-hydroxy-3-trityl-1,2,3a,4-tetrahydropyrrolo[2,3-b]indole-2-carbonyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoate | 868845-61-8

• 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: methyl (2S,3R)-2-[[(2S,3aS,8bR)-8b-hydroxy-3-trityl-1,2,3a,4-tetrahydropyrrolo[2,3-b]indole-2-carbonyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoate
• CAS: 868845-61-8
• 化学式: C₃₉H₄₃N₃O₅
• 分子量: 633.788
• InChiKey: GZRSTUFYVWAZOU-IIUPCCBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2S,3R)-2-[[(2S,3aS,8bR)-8b-hydroxy-3-trityl-1,2,3a,4-tetrahydropyrrolo[2,3-b]indole-2-carbonyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoate 在 lithium hydroxide 、 水 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N1-trityl-3α-hydroxypyrrolo[2,3-b]indolyl-O-^tbutyl-L-threonyl-S-trityl-L-cysteine 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
• 作为产物：
  描述：

  在 Oxone 、 碳酸氢钠 、 丙酮 作用下， 以 水 为溶剂， 以26%的产率得到methyl (2S,3R)-2-[[(2S,3aS,8bR)-8b-hydroxy-3-trityl-1,2,3a,4-tetrahydropyrrolo[2,3-b]indole-2-carbonyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoate
  参考文献：
  名称：

  通过原位生成的二甲基二环氧乙烷对N保护的色氨酸和色氨酸二肽进行有效的氧化，可得到适合于肽合成和随后的甲硫磷酰化反应的含六氢吡咯并吲哚啉的合成子

  摘要：

  含有与相应的单体HPI-α -氨基，通过一系列反应来制备酸（HPI -2-羧酸酯）二肽沿着系列hydroxypyrroloindoline的（HPI）ñ α -保护-色氨酸在水性或双相[水/环戊基甲基醚（CPME）含有过硫酸氢钾溶液®（过一硫酸钾）和丙酮。该程序避免了通常用于氧化吲哚的不稳定的二甲基二环氧乙烷（DMDO）的繁琐蒸馏。单体Ñ α -Boc-HPI-OH和Ñ α-Fmoc-Hpi-OH易于通过固相肽合成（SPPS）掺入含有半胱氨酸的肽中；在三氟乙酸（TFA）中，Hpi与半胱氨酸硫醇进行了分子内脱水缩合，从而提供了预期的类胰蛋氨酸交联。这种对生态和用户友好的氧化方法极大地简化了Hpi衍生物的合成，同时能够合成鬼笔环肽和甘露素（目前感兴趣的两种有效肽毒素）特有的色胺磷交联键。

  DOI：

  10.1007/s00726-016-2364-3

文献信息

• Efficient oxidation of N-protected tryptophan and tryptophanyl-dipeptides by in situ generated dimethyldioxirane provides hexahydropyrroloindoline-containing synthons suitable for peptide synthesis and subsequent tryptathionylation
  作者：Antoine Blanc、Fan Xia、Mihajlo Todorovic、David M. Perrin

  DOI：10.1007/s00726-016-2364-3

  日期：2017.2

  incorporated by solid-phase peptide synthesis (SPPS) into a peptide containing a cysteine; in trifluoroacetic acid (TFA), the Hpi underwent intramolecular dehydrative condensation with the cysteine thiol to afford the anticipated tryptathionine crosslink. This eco- and user-friendly oxidative methodology greatly simplifies the synthesis of Hpi derivatives while enabling the synthesis of tryptathionine crosslinks

  含有与相应的单体HPI-α -氨基，通过一系列反应来制备酸（HPI -2-羧酸酯）二肽沿着系列hydroxypyrroloindoline的（HPI）ñ α -保护-色氨酸在水性或双相[水/环戊基甲基醚（CPME）含有过硫酸氢钾溶液®（过一硫酸钾）和丙酮。该程序避免了通常用于氧化吲哚的不稳定的二甲基二环氧乙烷（DMDO）的繁琐蒸馏。单体Ñ α -Boc-HPI-OH和Ñ α-Fmoc-Hpi-OH易于通过固相肽合成（SPPS）掺入含有半胱氨酸的肽中；在三氟乙酸（TFA）中，Hpi与半胱氨酸硫醇进行了分子内脱水缩合，从而提供了预期的类胰蛋氨酸交联。这种对生态和用户友好的氧化方法极大地简化了Hpi衍生物的合成，同时能够合成鬼笔环肽和甘露素（目前感兴趣的两种有效肽毒素）特有的色胺磷交联键。
• 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.