二(甲硫基)焦霉毒素 | 74149-38-5

• 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
• 中文名称: 二(甲硫基)焦霉毒素
• 英文名称: bisdethiobis(methylthio)gliotoxin
• 英文别名: (3R,5aS,6S,10aR)-2,3,5a,6,10,10a-hexahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-3,10a-bis(methylsulfanyl)pyrazino[1,2-a]indole-1,4-dione；didehydrobisdethiobis(methylthio)gliotoxin；bis(dethio)bis(methylthio)gliotoxin；bis-dethiobis(methylthio)gliotoxin；Bisdethiobis(thiomethyl)gliotoxin；bisdethio(bismethylthio)gliotoxin；(3R,5aS,6S,10aR)-6-hydroxy-3-(hydroxymethyl)-2-methyl-3,10a-bis(methylsulfanyl)-6,10-dihydro-5aH-pyrazino[1,2-a]indole-1,4-dione
• CAS: 74149-38-5
• 化学式: C₁₅H₂₀N₂O₄S₂
• 分子量: 356.467
• InChiKey: OVBAGMZLGLXSBN-UOVKNHIHSA-N

物化性质

• 沸点：
  669.6±55.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn
• 危险类别码：
  R20/21/22
• 危险品运输编号：
  UN 1544
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 安全说明：
  S36
• WGK Germany：
  3
• 储存条件：
  室温

制备方法与用途

双(甲硫基)胶质毒素是一种比胶质毒素更加稳定和可靠的侵袭性曲霉病标志物，适用于诊断。

反应信息

• 作为反应物：
  描述：

  二(甲硫基)焦霉毒素 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 氯仿 为溶剂， 反应 6.0h， 以204 mg的产率得到5a,6-dehydrobisdethio-3,10a-bis(methylthio)gliotoxin
  参考文献：
  名称：

  bisdethiobis（甲硫基）胶霉毒素的生物合成，新的代谢物粘帚deliquescens

  摘要：

  Bisdethiobis（甲硫基）胶霉毒素（2）已被确定为一个无定形的，次要代谢物粘帚deliquescens和表征通过相应的二脱氢衍生物的结晶双-4-溴苯甲酸甲酯。新的代谢产物是通过还原和甲基化从胶体毒素（1）合成的。由L- [ U - 14 C]苯丙氨酸生物合成制备的[ 14 C]-（1）和-（2）的进料实验表明，形成了双脱硫双（甲硫基）gliotoxin（8.6％掺入），显然是不可逆的。葡甘聚糖中的gliotoxin。

  DOI：

  10.1039/p19800000119
• 作为产物：
  描述：

  Gliotoxin 在 sodium tetrahydroborate 、 S-腺苷-L-蛋氨酸 作用下， 以 异丙醇 为溶剂， 反应 0.5h， 以90.4%的产率得到二(甲硫基)焦霉毒素
  参考文献：
  名称：

  Opposed Effects of Enzymatic Gliotoxin N- and S-Methylations

  摘要：

  Gliotoxin (1), a virulence factor of the human pathogenic fungus Aspergillus fumigatus, is the prototype of epipoly(thiodioxopiperazine) (ETP) toxins. Here we report the discovery and functional analysis of two methyl transferases (MTs) that play crucial roles for ETP toxicity. Genome comparisons, knockouts, and in vitro enzyme studies identified a new S-adenosyl-l-methionine-dependent S-MT (TmtA) that is, surprisingly, encoded outside the gli gene cluster. We found that TmtA irreversibly inactivates ETP by S-alkylation and that this detoxification strategy appears to be not only limited to ETP producers. Furthermore, we unveiled that GliN functions as a freestanding amide N-MT. GliN-mediated amide methylation confers stability to ETP, damping the spontaneous formation of tri- and tetrasulfides. In addition, enzymatic N-alkylation constitutes the last step in gliotoxin biosynthesis and is a prerequisite for the cytotoxicity of the molecule. Thus, these specialized alkylating enzymes have dramatic and fully opposed effects: complete activation or inactivation of the toxin.

  DOI：

  10.1021/ja5033106

文献信息

• Studies of platelet activating factor (PAF) antagonists from microbial products. I. Bisdethiobis(methylthio)gliotoxin and its derivatives.
  作者：MASANORI OKAMOTO、KEIZO YOSHIDA、ITSUO UCHIDA、MOTOAKI NISHIKAWA、MASANOBU KOHSAKA、HATSUO AOKI

  DOI：10.1248/cpb.34.340

  日期：——

  A platelet activating factor (PAF) antagonist, designated as FR-49175, was isolated from fermentation products of Penicillium terlikowskii and identified as bisdethiobis(methylthio)-gliotoxin (1). The IC50 value of this compound for PAF-induced rabbit platelet aggregation was 8.4 μM.Some derivatives of bisdethiobis(methylthio)gliotoxin (1) were synthesized and their inhibitory activities of PAF-induced platelet aggregation were examined. Among these compounds, 5a, 6-anhydrobisdethio-3, 10a-bis(methylthio)gliotoxin (8) showed the most potent PAF inhibitory activity (IC50; 4.4 μM).

  一种血小板活化因子（PAF）拮抗剂被命名为 FR-49175，它是从青霉 terlikowskii 的发酵产物中分离出来的，并被鉴定为双二硫双（甲硫基）胶质毒素（1）。该化合物对 PAF 诱导的兔血小板聚集的 IC50 值为 8.4 μM。合成了一些双二硫双（甲硫基）胶质毒素（1）的衍生物，并考察了它们对 PAF 诱导的血小板聚集的抑制活性。在这些化合物中，5a, 6-脱水双二硫代-3, 10a-双（甲硫基）鬼臼毒素（8）显示出最强的 PAF 抑制活性（IC50；4.4 μM）。
• Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi
  作者：Katharine R. Watts、Joseline Ratnam、Kean-Hooi Ang、Karen Tenney、Jennifer E. Compton、James McKerrow、Phillip Crews

  DOI：10.1016/j.bmc.2010.02.034

  日期：2010.4

  Human African trypanosomiasis (HAT, commonly known as African sleeping sickness) is categorized as a neglected disease, as it afflicts >50,000 people annually in sub-saharan Africa, and there are few formal programs in the world focused on drug discovery approaches for this disease. In this study, we examined the crude extracts of two fungal strains (Aspergillus fumigatus and Nectria inventa) isolated from deep water sediment which provided >99% growth inhibition at 1 mu g/mL of Trypanosoma brucei, the causative parasite of HAT. A collection of fifteen natural products was supplemented with six semi-synthetic derivatives and one commercially available compound. Twelve of the compounds, each containing a diketopiperazine core, showed excellent activity against T. brucei (IC50 = 0.002-40 mu M), with selectivity over mammalian cells as great as 20-fold. The trypanocidal diketopiperazines were also tested against two cysteine protease targets Rhodesain and TbCatB, where five compounds showed inhibition activity at concentrations less than 20 mu M. A preliminary activity pattern is described and analyzed. (C) 2010 Elsevier Ltd. All rights reserved.
• UTIDA, ITSURO;OKAMOTO, MASANORI;JOSIDA, KEHJDZO
  作者：UTIDA, ITSURO、OKAMOTO, MASANORI、JOSIDA, KEHJDZO

  DOI：——

  日期：——
• METHODS AND COMPOSITIONS FOR DETECTING MYCOTOXINS
  申请人：ADVATECT DIAGNOSTICS, LLC

  公开号：US20220170931A1

  公开（公告）日：2022-06-02

  This invention relates to methods and compositions for detecting, quantifying, or identifying mycotoxins. More particularly, the invention relates to methods and compositions for detecting, quantifying, or identifying a gliotoxin, or a derivative thereof, a mycotoxin of a Penicillium species, or a mycotoxin of a Chaetomium species, in the tissues or body fluid samples of patients.
• [EN] METHODS AND COMPOSITIONS FOR DETECTING MYCOTOXINS<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR DÉTECTER DES MYCOTOXINES
  申请人：MEDICAL SERVICE CONSULTATION INT LLC

  公开号：WO2017049120A1

  公开（公告）日：2017-03-23

  This invention relates to methods and compositions for detecting, quantifying, or identifying mycotoxins. More particularly, the invention relates to methods and compositions for detecting, quantifying, or identifying a gliotoxin, or a derivative thereof, a mycotoxin of a Penicillium species, or a mycotoxin of a Chaetomium species, in the tissues or body fluid samples of patients.