Illudalic acid | 18508-77-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: Illudalic acid
• 英文别名: 3,6-dihydroxy-8,8-dimethyl-1-oxo-3,4,7,9-tetrahydrocyclopenta[h]isochromene-5-carbaldehyde
• CAS: 18508-77-5
• 化学式: C₁₅H₁₆O₅
• 分子量: 276.289
• InChiKey: BDEDPKFUFGCVCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 8-methoxy-2,2-dimethyl-1,2,3,5,6,7-hexahydro-s-indacene-4-carboxylate 在 chromium(VI) oxide 、 sodium periodate 、 溶剂黄146 作用下， 生成 Illudalic acid
  参考文献：
  名称：

  [EN] SELECTIVE PHOSPHATASE INHIBITORS BASED ON ILLUDALIC ACID
  [FR] INHIBITEURS SÉLECTIFS DE PHOSPHATASE À BASE DE L'ACIDE ILLUDALIQUE

  摘要：

  本公开提供基于伊卢达酸的新型选择性磷酸酶抑制剂化合物。本公开提供了一种简化的合成伊卢达酸的方法和一种合成磷酸酶抑制剂化合物的方法。本发明的方法提供了β-酮酰胺和酯的汇合苯环化，随后进行一锅法还原/水解序列。本发明提供的简洁合成方法使得能够快速组装本发明的伊卢达酸化合物，这些化合物是有效的蛋白酪氨酸磷酸酶受体D型（PTPRD）抑制剂。

  公开号：

  WO2022026717A1

文献信息

• Synthesis of illudalic acid and analogous phosphatase inhibitors
  作者：Harvey F. Fulo、Nicole J. Rueb、Robert Gaston、Paratchata Batsomboon、Kh Tanvir Ahmed、Amy M. Barrios、Gregory B. Dudley

  DOI：10.1039/d1ob02106k

  日期：——

  Developing an efficient, concise synthesis of the fungal natural product illudalic acid has been a long-standing challenge, made more pressing by the recent discovery that illudalic acid and analogs are selective phosphatase inhibitors. Syntheses of illudalic acid have become progressively more efficient over the decades yet remain strategically grounded in a 17-step synthesis reported in 1977. Here we validate

  开发一种高效、简明的真菌天然产物异丁烯酸合成方法一直是一个长期存在的挑战，最近发现异丁烯酸及其类似物是选择性磷酸酶抑制剂，这一挑战变得更加紧迫。几十年来，胡醛酸​​的合成已经变得越来越高效，但在战略上仍以 1977 年报道的 17 步合成为基础。在这里，我们验证了一个两步过程——收敛 [4 + 2] 苯并环化和一锅协调官能团操作—用于制备胡达酸的关键三功能药效基团。模块化构建模块可通过 2-3 个步骤轻松获得，从 3,3-二甲基环戊酮生成 5 个步骤的最长线性序列 (LLS)。通过类似的途径制备了一小部分具有相同药效团的类似茚满和四氢化萘。这些化合物有效且选择性地抑制蛋白酪氨酸磷酸酶 (PTP) 的人类白细胞共同抗原相关 (LAR) 亚家族。本文提供了支持假定的共价连接机制的证据。
• Synthesis and PTP Inhibitory Activity of Illudalic Acid and Its Methyl Ether, with Insights into Selectivity for LAR PTP over Other Tyrosine Phosphatases under Physiologically Relevant Conditions
  作者：Brandon S. McCullough、Paratchata Batsomboon、Kacey B. Hutchinson、Gregory B. Dudley、Amy M. Barrios

  DOI：10.1021/acs.jnatprod.9b00663

  日期：2019.12.27

  includes many attractive therapeutic targets, such as those in the leukocyte common antigen-related (LAR) subfamily of receptor PTPs. Synthesis and PTP inhibitory activity of illudalic acid and its methyl ether are described, with a focus on selective inhibition of LAR PTP relative to a small collection of other representative PTPs. The synthesis comprises 16 steps and provides illudalic acid in up to

  蛋白质酪氨酸磷酸酶（PTP）酶家族包括许多有吸引力的治疗靶标，例如受体PTP的白细胞常见抗原相关（LAR）亚家族中的靶标。描述了乙二酸及其甲基醚的合成和PTP抑制活性，重点是相对于少量其他代表性PTP选择性抑制LAR PTP。合成过程包括16个步骤，并从新戊烯基稠合的苯甲酸酯1（购自商业原料的20个步骤）中提供了高达12％的总产率的杜鹃酸。与以前的共价结合报道相一致，异丁酸的剂量依赖性（测得的IC50 = 2.1±0.2μM）和时间依赖性抑制LAR。杜鹃酸对LAR的抑制动力学与两步机制一致，其中抑制剂和酶首先非共价相互作用（KI = 130±50μM），然后以kinact = 1.3±0.4 min-1的速率共价连接。如本文所讨论的，运动/ KI之比104对应于0.5分钟的∞1/2。在我们的剂量反应分析中，发现伊达酸的酚甲基醚效力较低（测得的IC50 = 55±6μM），但对LAR的选择性
• Total synthesis of illudinine, illudalic acid, and illudacetalic acid
  作者：R. B. Woodward、Thomas R. Hoye

  DOI：10.1021/ja00466a038

  日期：1977.11
• Illudalic acid as a potential LAR inhibitor: Synthesis, SAR, and preliminary studies on the mechanism of action
  作者：Qing Ling、Yue Huang、Yueyang Zhou、Zhengliang Cai、Bing Xiong、Yahui Zhang、Lanping Ma、Xin Wang、Xin Li、Jia Li、Jingkang Shen

  DOI：10.1016/j.bmc.2008.06.014

  日期：2008.8

  A novel synthesis of the human leukocyte common antigen-related (LAR) phosphatase inhibitor, illudalic acid, has been achieved by a route more amenable to structure modi. cations. A series of simpler analogues of illudalic acid was synthesized and evaluated for potency in inhibiting LAR. The structure -activity relationship (SAR) study has shown that the 5-formyl group and the hemi-acetal lactone are crucial for effective inhibition of LAR activity, and are the key pharmacophores of illudalic acid. The fused dimethylcyclopentene ring moiety evidently helps to enhance the potency of illudalic acid against LAR. A preliminary study of the mechanism of action of illudalic acid against LAR was conducted using electrospray ionization mass spectrometry (ESI-MS) and molecular docking techniques. The results are in full agreement with the described mechanism. (C) 2008 Elsevier Ltd. All rights reserved.
• [EN] SELECTIVE PHOSPHATASE INHIBITORS BASED ON ILLUDALIC ACID<br/>[FR] INHIBITEURS SÉLECTIFS DE PHOSPHATASE À BASE DE L'ACIDE ILLUDALIQUE
  申请人：WEST VIRGINIA UNIV BOARD OF GOVERNORS ON BEHALF OF WEST VIRGINIA UNIV

  公开号：WO2022026717A1

  公开（公告）日：2022-02-03

  The present disclosure provides novel selective phosphatase inhibitor compounds based on illudalic acid. The present disclosure provides a streamlined method of synthesizing illudalic acid and a method for synthesizing phosphatase inhibitor compounds. The method of this invention provides convergent benzannulation of β-keto amides and esters, followed by a one-pot reduction / hydrolysis sequence. The concise synthetic approach provided by this invention enables rapid assembly of illudalog compounds of this invention that are potent protein tyrosine phosphatase receptor-type D (PTPRD) inhibitors.

  本公开提供基于伊卢达酸的新型选择性磷酸酶抑制剂化合物。本公开提供了一种简化的合成伊卢达酸的方法和一种合成磷酸酶抑制剂化合物的方法。本发明的方法提供了β-酮酰胺和酯的汇合苯环化，随后进行一锅法还原/水解序列。本发明提供的简洁合成方法使得能够快速组装本发明的伊卢达酸化合物，这些化合物是有效的蛋白酪氨酸磷酸酶受体D型（PTPRD）抑制剂。