{"title":"具有抗神经炎活性的两种二聚体萘醌-环氧环己烯酮加合物--来自等足类真菌 Herpotrichia sp.","authors":"Yi-Jie Zhai, Zhen-Zhen Zhou, Wen-Ji Wang, Xin-Yu Wang, Zi-Jue Wang, Guang-Zhi Dai, Xinxiang Lei, Wen-Li Li, Jin-Ming Gao and Wen-Bo Han","doi":"10.1039/D4QO01256A","DOIUrl":null,"url":null,"abstract":"<p >Herpotriquinones A and B (<strong>1</strong> and <strong>2</strong>), two pyran-bridged naphthoquinone–epoxycyclohexenone dimers with an unprecedented 6/6/6/6/6-fused pentacyclic ring skeleton, along with two known precursors (<strong>3</strong> and <strong>4</strong>) were isolated from the isopod-associated fungus <em>Herpotrichia</em> sp. SF09. Their structures were elucidated by means of spectroscopic data, single-crystal X-ray diffraction, and quantum chemical calculations of <small><sup>13</sup></small>C NMR and electronic circular dichroism (ECD). Herpotriquinones A and B (<strong>1</strong> and <strong>2</strong>) represent the first examples of polyketide heterodimers biogenetically constructed by a molecule of epoxycyclohexenone with a naphthoquinone unit <em>via</em> a rare formal oxa-[3 + 3] cycloaddition. The density functional theory (DFT) calculations and intermediate-trapping experiment facilitated the proposal of the biosynthetic pathway for these polyketides. In addition, compounds <strong>1</strong> and <strong>2</strong> were found to be potent anti-neuroinflammatory agents in CuSO<small><sub>4</sub></small>-induced zebrafish and lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Meanwhile, western blot analysis suggested that <strong>1</strong> and <strong>2</strong> could ameliorate the neuroinflammation by suppressing the activation of the NF-κB and MAPK signaling pathways.</p>","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":" 21","pages":" 6069-6077"},"PeriodicalIF":4.7000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Herpotriquinones A and B, two dimeric naphthoquinone–epoxycyclohexenone adducts with anti-neuroinflammatory activity from the isopod-associated fungus Herpotrichia sp. SF09†\",\"authors\":\"Yi-Jie Zhai, Zhen-Zhen Zhou, Wen-Ji Wang, Xin-Yu Wang, Zi-Jue Wang, Guang-Zhi Dai, Xinxiang Lei, Wen-Li Li, Jin-Ming Gao and Wen-Bo Han\",\"doi\":\"10.1039/D4QO01256A\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Herpotriquinones A and B (<strong>1</strong> and <strong>2</strong>), two pyran-bridged naphthoquinone–epoxycyclohexenone dimers with an unprecedented 6/6/6/6/6-fused pentacyclic ring skeleton, along with two known precursors (<strong>3</strong> and <strong>4</strong>) were isolated from the isopod-associated fungus <em>Herpotrichia</em> sp. SF09. Their structures were elucidated by means of spectroscopic data, single-crystal X-ray diffraction, and quantum chemical calculations of <small><sup>13</sup></small>C NMR and electronic circular dichroism (ECD). Herpotriquinones A and B (<strong>1</strong> and <strong>2</strong>) represent the first examples of polyketide heterodimers biogenetically constructed by a molecule of epoxycyclohexenone with a naphthoquinone unit <em>via</em> a rare formal oxa-[3 + 3] cycloaddition. The density functional theory (DFT) calculations and intermediate-trapping experiment facilitated the proposal of the biosynthetic pathway for these polyketides. In addition, compounds <strong>1</strong> and <strong>2</strong> were found to be potent anti-neuroinflammatory agents in CuSO<small><sub>4</sub></small>-induced zebrafish and lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Meanwhile, western blot analysis suggested that <strong>1</strong> and <strong>2</strong> could ameliorate the neuroinflammation by suppressing the activation of the NF-κB and MAPK signaling pathways.</p>\",\"PeriodicalId\":97,\"journal\":{\"name\":\"Organic Chemistry Frontiers\",\"volume\":\" 21\",\"pages\":\" 6069-6077\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organic Chemistry Frontiers\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/qo/d4qo01256a\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Chemistry Frontiers","FirstCategoryId":"92","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/qo/d4qo01256a","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
摘要
从等足类真菌 Herpotrichia sp. SF09 中分离出了 Herpotriquinones A 和 B(1 和 2),这是两种吡喃桥接的萘醌-环氧环己烯酮二聚体,具有前所未有的 6/6/6/6/6 融合五环骨架,以及两种已知的前体(3 和 4)。通过光谱数据、单晶 X 射线衍射以及 13C NMR 和电子圆二色性(ECD)的量子化学计算,阐明了它们的结构。Herpotriquinones A 和 B(1 和 2)代表了由环氧环己烯酮分子与萘醌单元通过罕见的形式氧杂-[3 + 3]环加成而生物构建的多酮异构体的第一个实例。密度泛函理论(DFT)计算和中间俘获实验有助于提出这些多酮化合物的生物合成途径。此外,研究还发现化合物1和2在CuSO4诱导的斑马鱼和脂多糖(LPS)刺激的BV-2小胶质细胞中具有强效的抗神经炎作用。同时,Western印迹分析表明,1和2可通过抑制NF-κB和MAPK信号通路的激活来改善神经炎症。
Herpotriquinones A and B, two dimeric naphthoquinone–epoxycyclohexenone adducts with anti-neuroinflammatory activity from the isopod-associated fungus Herpotrichia sp. SF09†
Herpotriquinones A and B (1 and 2), two pyran-bridged naphthoquinone–epoxycyclohexenone dimers with an unprecedented 6/6/6/6/6-fused pentacyclic ring skeleton, along with two known precursors (3 and 4) were isolated from the isopod-associated fungus Herpotrichia sp. SF09. Their structures were elucidated by means of spectroscopic data, single-crystal X-ray diffraction, and quantum chemical calculations of 13C NMR and electronic circular dichroism (ECD). Herpotriquinones A and B (1 and 2) represent the first examples of polyketide heterodimers biogenetically constructed by a molecule of epoxycyclohexenone with a naphthoquinone unit via a rare formal oxa-[3 + 3] cycloaddition. The density functional theory (DFT) calculations and intermediate-trapping experiment facilitated the proposal of the biosynthetic pathway for these polyketides. In addition, compounds 1 and 2 were found to be potent anti-neuroinflammatory agents in CuSO4-induced zebrafish and lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Meanwhile, western blot analysis suggested that 1 and 2 could ameliorate the neuroinflammation by suppressing the activation of the NF-κB and MAPK signaling pathways.
期刊介绍:
Organic Chemistry Frontiers is an esteemed journal that publishes high-quality research across the field of organic chemistry. It places a significant emphasis on studies that contribute substantially to the field by introducing new or significantly improved protocols and methodologies. The journal covers a wide array of topics which include, but are not limited to, organic synthesis, the development of synthetic methodologies, catalysis, natural products, functional organic materials, supramolecular and macromolecular chemistry, as well as physical and computational organic chemistry.