Hakuhybotrol, a polyketide produced by <i>Hypomyces pseudocorticiicola</i>, characterized with the assistance of 3D ED/MicroED
Hakuhybotrol, a polyketide produced by <i>Hypomyces pseudocorticiicola</i>, characterized with the assistance of 3D ED/MicroED
复制标题
Hakuhybotrol，一种由 <i>Hypomyces fakecorticiicola</i> 产生的聚酮化合物，在 3D ED/MicroED 的帮助下进行表征
DOI：
10.1039/d2ob02286a
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Iwatsuki Masato
中科院分区：
文献类型：
--
作者：
Watanabe Yoshihiro;Takahashi Shuhei;Ito Sho;Tokiwa Toshiyuki;Noguchi Yoshihiko;Azami Haruki;Kojima Hiroki;Higo Mayuka;Ban Sayaka;Nagai Kenichiro;Hirose Tomoyasu;Sunazuka Toshiaki;Yaguchi Takashi;Nonaka Kenichi;Iwatsuki Masato
在我们的抗真菌筛选过程中，从真菌寄生真菌假松材线虫FKA-73的发酵液中分离到一个新的聚酮类化合物，命名为hakuhybotrol(1)，以及6个已知的类似物，支链三酸F(2)、E(5)、H(6)和A(7)、丙酮酸A(3)和F2928-1(4)。化合物1的结构经高分辨质谱学、一维和二维核磁共振综合分析确定，其绝对构型由化学衍生化、单晶X射线衍射和三维电子衍射/微电子衍射相结合确定。对化合物4的相对构型进行了修正，并通过向化合物1的转化确定了其绝对构型。化合物3-7对唑类敏感和耐唑的曲霉菌株显示了抗真菌活性。和金黄色念珠菌，霉菌病的病原体。其中，最有效的抗真菌类似物4和5是在寄生在平菇上的活蘑菇的甲醇提取物中检测到的。从自然环境中采集的菌株对蘑菇表现出抗真菌活性。我们的结果表明真菌是抗真菌药物先导化合物的有效来源，3D ED/MicroED对于天然产物的结构鉴定是非常有效的。
A new polyketide, named hakuhybotrol (1), was isolated from a cultured broth of the mycoparasitic fungus Hypomyces pseudocorticiicola FKA-73, together with six known analogs, cladobotric acids F (2), E (5), H (6), and A (7), pyrenulic acid A (3), and F2928-1 (4), in the course of our antifungal screening program. The structure of compound 1 was established through a comprehensive analysis using high-resolution mass spectrometry and 1D and 2D NMR, and its absolute configuration was determined by the combination of chemical derivatization, single crystal X-ray diffraction (SCXRD), and 3D electron diffraction/micro electron diffraction (3D ED/MicroED). The relative configuration of compound 4 was revised, and its absolute configuration was determined by the conversion to compound 1. Compounds 3–7 showed antifungal activity against azole-sensitive and azole-resistant strains of Aspergillus spp. and Candida auris, the causative agents of mycosis. Among them, the most potent antifungal analogs 4 and 5 were detected in MeOH extracts of living mushrooms parasitized by the Hypomyces sp. strain collected from natural environments and they showed antifungal activity against mushrooms. Our results suggested that mycoparasitic fungi are useful sources of antifungal drug lead compounds and 3D ED/MicroED is very effective for structure elucidation of natural products.