S-(-)-methyl 2-α-[N-t-butoxycarbonyl]amino-β-(indol-3-yl)propionyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate | 354764-99-1

• 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: S-(-)-methyl 2-α-[N-t-butoxycarbonyl]amino-β-(indol-3-yl)propionyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
• 英文别名: (3S)-2-(Boc-L-tryptophanyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester；methyl (3S)-2-[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate
• CAS: 354764-99-1
• 化学式: C₂₉H₃₂N₄O₅
• 分子量: 516.597
• InChiKey: DGEZMQAIBSDEFU-ZCYQVOJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  S-(-)-methyl 2-α-[N-t-butoxycarbonyl]amino-β-(indol-3-yl)propionyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 1.0h， 以90%的产率得到(3S)-N-(Boc-L-tryptophanyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid
  参考文献：
  名称：

  A Class of 3S-2-Aminoacyltetrahydro-β-carboline-3-carboxylic Acids: Their Facile Synthesis, Inhibition for Platelet Activation, and High in Vivo Anti-Thrombotic Potency

  摘要：

  3S-Tetrahydro-beta-carboline-3-carboxylic acid (TCCA) effectively inhibits ADP-induced platelet activation. This paper used TCCA as a lead, modified its 2-position with amino acids, and provided 20 novel 3S-2-aminoacyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids (5a-t). With the in vitro assay, it was demonstrated that this modification diminished the IC(50) values from 701 nM of TCCA to 10 nM of 5a-t. With the in vivo assay, it was demonstrated that this modification reduced the efficacious dose from 5.0 mu mol/kg of TCCA to 0.1 mu mol/kg of 5a-t. Comparing the Cerius(2) based conformation of them with that of their analogues, the 3-position modified TCCA, it was suggested that the comparatively unfolded conformation was one of the important factors of enhancing the in vivo antithrombotic potency.

  DOI：

  10.1021/jm901816j
• 作为产物：
  描述：

  (S)-2,3,4,9-四氢-1H-吡啶[3,4-b]吲哚-3-羧酸 在 氯化亚砜 、 2-bromo-1-ethylpyridin-1-ium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 S-(-)-methyl 2-α-[N-t-butoxycarbonyl]amino-β-(indol-3-yl)propionyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Toward breast cancer resistance protein (BCRP) inhibitors: design, synthesis of a series of new simplified fumitremorgin C analogues

  摘要：

  In this study, we report the design and synthesis of a series of new simplified fumitremorgin C analogues. The preliminary biological study indicated some of these simplified fumitremorgin C might be developed into breast cancer resistance inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.04.045

文献信息

• Microwave assisted stereospecific synthesis of (S)-3-substituted 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-diones
  作者：Suresh K Pandey、Keshav K Awasthi、Anil K Saxena

  DOI：10.1016/s0040-4020(01)00334-9

  日期：2001.5

  A new easy way of preparing (S)-3-substituted 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-diones, an important intermediate compound, is described using microwave irradiation supported on silica gel. The reaction is generalised and good to excellent yields of enantiomerically pure products are obtained.

  一种制备（S）-3-取代的2,3,6,7,12,12a-六氢吡嗪并[1'，2'：1,6]吡啶[3,4- b ]吲哚-1,4的简便方法使用载于硅胶上的微波辐射描述了重要的中间体化合物-二酮。反应被普遍进行，并且获得对映体纯产物的良好至极好的收率。
• Data Science-Driven Analysis of Substrate-Permissive Diketopiperazine Reverse Prenyltransferase NotF: Applications in Protein Engineering and Cascade Biocatalytic Synthesis of (−)-Eurotiumin A
  作者：Samantha P. Kelly、Vikram V. Shende、Autumn R. Flynn、Qingyun Dan、Ying Ye、Janet L. Smith、Sachiko Tsukamoto、Matthew S. Sigman、David H. Sherman

  DOI：10.1021/jacs.2c06631

  日期：2022.10.26

  functionalization prevalent in the biosynthesis of a diverse array of biologically active bacterial, fungal, plant, and metazoan diketopiperazine (DKP) alkaloids. Toward the development of a unified strategy for biocatalytic construction of prenylated DKP indole alkaloids, we sought to identify and characterize a substrate-permissive C2 reverse prenyltransferase (PT). As the first tailoring event within the biosynthesis

  异戊二烯转移是一种早期碳氢键 (C–H) 功能化，普遍存在于多种具有生物活性的细菌、真菌、植物和后生动物二酮哌嗪 (DKP) 生物碱的生物合成中。为了开发异戊二烯化 DKP 吲哚生物碱生物催化构建的统一策略，我们试图鉴定和表征底物允许的 C2 反向异戊二烯基转移酶 (PT)。作为细胞毒性诺托酰胺代谢物生物合成中的第一个剪裁事件，PT NotF 催化短维胺 F 的 C2 反向异戊烯转移。解析 NotF 的晶体结构（与天然底物和异戊烯供体模拟物二甲基烯丙基 S-硫代二磷酸 (DMSPP) 形成复合物）揭示了一个大的，暴露于溶剂的活性位点，提示 NotF 可能具有非常广泛的底物范围。为了评估 NotF 的底物选择性，我们合成了一组 30 种空间和电子分化的色氨酸 DKP，其中大部分在合成有用的转化（2 至 >99%）中被 NotF 选择性异戊二烯化。该底物库的定量表示和描述性统计模型的开发提供了对
• Toward breast cancer resistance protein (BCRP) inhibitors: design, synthesis of a series of new simplified fumitremorgin C analogues
  作者：Guofeng Wu、Jiawang Liu、Lanrong Bi、Ming Zhao、Chao Wang、Michèle Baudy-Floc'h、Jingfang Ju、Shiqi Peng

  DOI：10.1016/j.tet.2007.04.045

  日期：2007.6

  In this study, we report the design and synthesis of a series of new simplified fumitremorgin C analogues. The preliminary biological study indicated some of these simplified fumitremorgin C might be developed into breast cancer resistance inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.
• A Class of 3<i>S</i>-2-Aminoacyltetrahydro-β-carboline-3-carboxylic Acids: Their Facile Synthesis, Inhibition for Platelet Activation, and High in Vivo Anti-Thrombotic Potency
  作者：Jiawang Liu、Xueyun Jiang、Ming Zhao、Xiaoyi Zhang、Meiqing Zheng、Li Peng、Shiqi Peng

  DOI：10.1021/jm901816j

  日期：2010.4.22

  3S-Tetrahydro-beta-carboline-3-carboxylic acid (TCCA) effectively inhibits ADP-induced platelet activation. This paper used TCCA as a lead, modified its 2-position with amino acids, and provided 20 novel 3S-2-aminoacyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids (5a-t). With the in vitro assay, it was demonstrated that this modification diminished the IC(50) values from 701 nM of TCCA to 10 nM of 5a-t. With the in vivo assay, it was demonstrated that this modification reduced the efficacious dose from 5.0 mu mol/kg of TCCA to 0.1 mu mol/kg of 5a-t. Comparing the Cerius(2) based conformation of them with that of their analogues, the 3-position modified TCCA, it was suggested that the comparatively unfolded conformation was one of the important factors of enhancing the in vivo antithrombotic potency.