asperlicin C | 93413-06-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 嘧啶二氮卓类
• 英文名称: asperlicin C
• 英文别名: (7S)-7-(1H-indol-3-ylmethyl)-6,7-dihydroquinazolino[3,2-a][1,4]benzodiazepine-5,13-dione
• CAS: 93413-06-0
• 化学式: C₂₅H₁₈N₄O₂
• 分子量: 406.444
• InChiKey: BUTFEAMXSRJHIM-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  asperlicin C 在 氧气 作用下， 生成 阿斯普尼辛E
  参考文献：
  名称：

  Assembly of Asperlicin Peptidyl Alkaloids from Anthranilate and Tryptophan: A Two-Enzyme Pathway Generates Heptacyclic Scaffold Complexity in Asperlicin E

  摘要：

  Members of the asperlicin family of fungal metabolites produced by Aspergillus alliaceus are known potent CCKA antagonists. Herein, we report the identification of the gene cluster responsible for directing their biosynthesis. We validate and probe the pathway by genetic manipulation, and provide the first biochemical characterization of the oxidative cyclization en route to the heptacyclic asperlicin E by reconstituting the activity of the FAD depend monooxygenase AspB. This report provides the first genetic characterization of a NRPS assembly line that efficiently activates two anthranilate building blocks and illustrates the remarkably efficient biosynthesis of the complex heptacyclic asperlicin E.

  DOI：

  10.1021/ja308371z
• 作为产物：
  描述：

  o-azidobenzoyl chloride 在 4-二甲氨基吡啶 、 三丁基膦 、 三乙胺 作用下， 以 苯 为溶剂， 生成 asperlicin C
  参考文献：
  名称：

  Total Syntheses of (−)-Asperlicin and (−)-Asperlicin C

  摘要：

  DOI：

  10.1021/ja9809408

文献信息

• Procedure—economical enantioselective total syntheses of asperlicins C and E
  作者：Pei-Qiang Huang、Yu Wang、Shi-Peng Luo、Hui Geng、Yuan-Ping Ruan、Ai-E Wang

  DOI：10.1016/j.tetlet.2015.01.084

  日期：2015.3

  employment of LVT for the synthesis of asperlicin C, which allowed accessing asperlicin C in >99% enantioselectivity. Asperlicin C was converted, in one-pot, into asperlicin E and 2,3-di-epi-asperlicin E by dimethyl dioxirane (DMDO)-mediated tandem reactions. The use of DMDO as a green, cheap, and easily available oxidant to replace the photochemical method renders the synthesis of asperlicin E experimentally

  我们报告了一种经济高效的非肽CCK拮抗剂曲霉菌素C和E的高对映选择性和保护基自由合成的方法。从l-色氨酸开始，分三步完成了曲霉菌素C的合成，其特征是低-价钛（LVT：TiCl 4 -Zn组合）介导的邻硝基苯甲酰胺的还原环化反应，以构建（3 H）-喹唑啉-4-酮部分。这是LVT首次用于合成Asperlicin C的方法，它允许以> 99％的对映选择性进入AsperlicinC。一锅法将曲霉菌素C转化为曲霉菌素E和2,3-二表位-asperlicin E由二甲基二环氧乙烷（DMDO）介导的串联反应。DMDO作为一种绿色，廉价且易于获得的氧化剂来代替光化学方法，在实验上方便了合成Asperlicin E的过程。
• Low-Valent Titanium-Mediated Enantioselective Synthesis of Quinazolinone Alkaloids Circumdatins F, H, and Analogs
  作者：Shi-Peng Luo、Hui Geng、Yu Wang、Pei-Qiang Huang

  DOI：10.1002/cjoc.201400849

  日期：2015.6

  We report the concise and protecting‐group‐free enantioselective total syntheses of circumdatins F and H. In view of the extreme importance of analogs of quinazolinone alkaloids in drug research and discovery, four analogs of bioactive quinazolinobenzodiazepine alkaloids, including demethoxycircumdatin H (12) and N‐demethylbenzomalvin A (13), have been synthesized. The method is based on the low‐valent

  我们报告了简明的和无保护基团的对映体F和H的对映选择性总合成。鉴于喹唑啉酮生物碱的类似物在药物研究和发现中极为重要，因此有四种生物活性喹唑啉酮苯二氮卓生物碱的类似物，包括脱甲氧基环丁啶H（12）和N-去甲基苯并丙氨酸A（13）已合成。该方法基于酰亚胺与邻硝基苯甲酰亚胺的低价钛促进的分子内还原偶联，在温和条件下可生成喹唑啉代[3,2- a ] [1,4]苯并二氮杂pine。此外，七环脱水紫精素E（16）是通过NCS介导的脱水环化反应从阿斯匹林菌素C合成的。
• Total synthesis of asperlicin C, circumdatin F, demethylbenzomalvin A, demethoxycircumdatin H, sclerotigenin, and other fused quinazolinones
  作者：Ming-Chung Tseng、Huei-Yun Yang、Yen-Ho Chu

  DOI：10.1039/b910545j

  日期：——

  Using scandium triflate and microwaves, the direct double dehydrocyclization of anthranilate-containing tripeptides was achieved, affording the total syntheses of (i) quinazolino[3,2-a]benzodiazepinediones (1a–f), (ii) diazepino[2,1-b]quinazolinediones (2a–e), and (iii) pyrazino[2,1-b]quinazolinediones (3a–e) with good overall isolated yields (23–43%, 37–47% and 31–56%, respectively). Among the quinazolino[3,2-a]benzodiazepinediones synthesized, 1a (sclerotigenin), 1b (circumdatin F), and 1f (asperlicin C) are natural products.

  使用氟化铈和微波，成功实现了含有氨基苯甲酸的三肽的直接双脱氢环化，获得了以下化合物的整体合成：（i）喹唑啉[3,2-a]苯二氮杂杂环二酮（1a-f），（ii）二氮杂氟[2,1-b]喹唑啉二酮（2a-e），以及（iii）吡嗪[2,1-b]喹唑啉二酮（3a-e），它们的整体分离产率分别为23-43%，37-47%和31-56%。在合成的喹唑啉[3,2-a]苯二氮杂杂环二酮中，1a（紫锈碱）、1b（环夭碱F）和1f（曲霉素C）是天然产物。
• An Iterative, Bimodular Nonribosomal Peptide Synthetase that Converts Anthranilate and Tryptophan into Tetracyclic Asperlicins
  作者：Xue Gao、Wei Jiang、Gonzalo Jiménez-Osés、Moon Seok Choi、Kendall N. Houk、Yi Tang、Christopher T. Walsh

  DOI：10.1016/j.chembiol.2013.04.019

  日期：2013.7

  anthranilate (Ant) into a pair of tetracyclic peptidyl alkaloids asperlicin C and D in a ratio of 10:1. The first module of AspA activates and processes two molecules of Ant iteratively to generate a tethered Ant-Ant-Trp-S-enzyme intermediate on module two. Release is postulated to involve tandem cyclizations, in which the first step is the macrocyclization of the linear tripeptidyl-S-enzyme, by the terminal

  来自葱曲霉的双模块 276 kDa 非核糖体肽合成酶 AspA，在酿酒酵母中异源表达，将色氨酸和两分子芳香族 β-氨基酸邻氨基苯甲酸 (Ant) 转化为一对四环肽基生物碱 D: asperlicin D: asperlicin . AspA 的第一个模块反复激活和处理两个 Ant 分子，以在模块 2 上生成一个连接的 Ant-Ant-Trp-S-酶中间体。假定释放涉及串联环化，其中第一步是线性三肽基-S-酶的大环化，通过末端缩合 (CT) 域生成区域异构四环 asperlicin 支架。
• Indol-3-yl-quinazolino-1,4-benzodiazepin-5,13-diones, process for their preparation and pharmaceutical compositions containing them
  申请人：Merck & Co., Inc.

  公开号：EP0189803A1

  公开（公告）日：1986-08-06

  Novel indol-3-yl-quinazolino-1,4-benzo-diazepin-5,13-dionea, which are antagonists of the function of cholecystokinins (CCK), to the preparation of these compounds from compounds prepared by aerobic fermentation of certain Aspergillus alliaceus strains, and to the use of these compounds to antagonize the function of CCK, which antagonism is useful, e.g., for the treatment and prevention of disorders of the gastrointestinal, central nervous and appetlte-regulatory systems of mammals, especially of humans.

  新型吲哚-3-基喹唑啉-1,4-苯并二氮杂卓-5,13-二酮，是胆囊收缩素（CCK）功能的拮抗剂，从某些曲霉菌株有氧发酵制备的化合物中制备出这些化合物，并利用这些化合物拮抗CCK的功能，这种拮抗作用有助于，例如治疗和预防哺乳动物，特别是人类的胃肠道、中枢神经和食欲调节系统疾病。