methyl 2-[(2S)-3-(1H-indol-3-yl)-2-[(triphenylmethyl)amino]propanamido]acetate | 868845-72-1

• 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 2-[(2S)-3-(1H-indol-3-yl)-2-[(triphenylmethyl)amino]propanamido]acetate
• 英文别名: (S)-methyl 2-(3-(1H-indol-3-yl)-2-(tritylamino)propanamido)acetate；Trt-Trp-Gly-OMe；Tr-Trp-Gly-OMe；N-Trt-Trp-Gly-OMe
• CAS: 868845-72-1
• 化学式: C₃₃H₃₁N₃O₃
• 分子量: 517.627
• InChiKey: UVRZGXCWJYYATF-PMERELPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.95
• 重原子数：
  39.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  83.22
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 2-[(2S)-3-(1H-indol-3-yl)-2-[(triphenylmethyl)amino]propanamido]acetate 在 二甲基二环氧乙烷 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 1.0h， 以70%的产率得到methyl 2-(3a-hydroxy-1-trityl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxamido)acetate
  参考文献：
  名称：

  [EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE
  [FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE

  摘要：

  Amernita毒素的衍生物的化学式（I），其中，化学式（a）中的R 1、R 2、R 3、R 4、R 5、R 6、R 7、R 8、R 9、R 10、X、L、m、n和Q在此处被定义。这些衍生物的制备。这些衍生物在靶向治疗癌症、自身免疫性疾病和传染病中的治疗用途。

  公开号：

  WO2017046658A1
• 作为产物：
  描述：

  L-色氨酸 在 三甲基氯硅烷 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 44.5h， 生成 methyl 2-[(2S)-3-(1H-indol-3-yl)-2-[(triphenylmethyl)amino]propanamido]acetate
  参考文献：
  名称：

  [EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE
  [FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE

  摘要：

  Amernita毒素的衍生物的化学式（I），其中，化学式（a）中的R 1、R 2、R 3、R 4、R 5、R 6、R 7、R 8、R 9、R 10、X、L、m、n和Q在此处被定义。这些衍生物的制备。这些衍生物在靶向治疗癌症、自身免疫性疾病和传染病中的治疗用途。

  公开号：

  WO2017046658A1

文献信息

• [EN] A CONJUGATE OF AN AMANITA TOXIN WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UNE TOXINE D'AMANITE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020155017A1

  公开（公告）日：2020-08-06

  Provided herein is the conjugation of an amanita toxin compound to a cell-binding molecule with branched linkers for having better targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of an amanita molecule to a cell-binding ligand, as well as methods of using the conjugate in targets treatment of cancer, infection and autoimmune disease.

  本文提供了一种将鹅膏菌毒素化合物与具有分支连接物的细胞结合分子结合，以实现更好地针对异常细胞进行治疗。它还涉及将鹅膏菌分子与细胞结合配体结合的分支连接方法，以及在癌症、感染和自身免疫疾病治疗中使用该结合物的方法。
• 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。
• 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。
• Synthesis and Activation of Bench-Stable 3a-Fluoropyrroloindolines as Latent Electrophiles for the Synthesis of C-2-Thiol-Substituted Tryptophans and C-3a-Substituted Pyrroloindolines
  作者：Alla Pryyma、Yong Jia Bu、Yonnie Wai、Brian O. Patrick、David M. Perrin

  DOI：10.1021/acs.orglett.9b02972

  日期：2019.10.18

  Indole dearomatization of tryptophan represents a key approach in the synthesis of indole containing alkaloids. Although the reactivity of C-3a-bromo-, 3a-iodo-, and 3a-chloropyrroloindolines has been explored, the utility and reactivity of C-3a-fluoropyrroloindolines has remained untapped. Here we induce the C-F bond to undergo a S_n1-like reaction. We demonstrate the utility of 3a-fluoropyrroloindoline to access C-2-thiol-substituted tryptophans and C-3a-substituted pyrroloindolines under mild conditions in high yield. A range of N^α-protecting groups and free -COOH are well-tolerated.
• 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.