普诺醇酮 A-G，具有不寻常的 6/6/6/6/6 螺戊烷五环骨架的促血管生成异香豆素衍生物，来自内生真菌 Phomopsis prunorum。

Prunolactones A-G, proangiogenic isocoumarin derivatives with an unusual 6/6/6/6/6 spiropentacyclic skeleton from the endophytic fungus Phomopsis prunorum.

机构信息

Hubei Key Laboratory of Natural Product Research and Development (China Three Gorges University), College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, People's Republic of China; Key Laboratory of Functional Yeast, China National Light Industry, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, People's Republic of China.

出版信息

Bioorg Chem. 2023 Dec;141:106898. doi: 10.1016/j.bioorg.2023.106898. Epub 2023 Oct 2.

DOI:10.1016/j.bioorg.2023.106898

PMID:37801783

Abstract

Seven novel isocoumarins, prunolactones A-G (1-7), featuring an unusual 6/6/6/6/6 spiropentacyclic skeleton, together with two biosynthetic precursors phomopsilactone (8) and methyl 3-epi-shikimate (9), were isolated from the endophytic fungus Phomopsis prunorum guided by UPLC-QTOF-MS and H NMR spectroscopic analytical techniques. Their structures including absolute configurations of 1-7 were elucidated based on extensive spectroscopic data, X-ray diffraction analysis, and ECD calculations. Biogenetically, compounds 1-7 are proposed to be derived from polyketide and shikimate pathways via key intermolecular Diels - Alder reactions. Compounds 2, 3, and 7 showed significant in vivo proangiogenic activity in transgenic zebrafish.

摘要

从内生真菌 Phomopsis prunorum 中分离到 7 种新型异香豆素，包括 prunolactones A-G（1-7），它们具有不寻常的 6/6/6/6/6 螺环五环骨架，以及两种生物合成前体 phomopsilactone（8）和甲基 3-epi-莽草酸（9）。这些化合物的结构包括 1-7 的绝对构型，是根据广泛的光谱数据、X 射线衍射分析和 ECD 计算来确定的。生物合成上，化合物 1-7 被认为是通过关键的分子间 Diels-Alder 反应，从聚酮体和莽草酸途径衍生而来的。化合物 2、3 和 7 在转基因斑马鱼中表现出显著的体内促血管生成活性。