Bipolarolides A–G: Ophiobolin‐Derived Sesterterpenes with Three New Carbon Skeletons from Bipolaris sp. TJ403‐B1. Issue 35 (30th July 2019)

• Record Type: Journal Article
• Authors: Liu, Mengting; Sun, Weiguang; Shen, Ling; He, Yan; Liu, Junjun; Wang, Jianping; Hu, Zhengxi; Zhang, Yonghui
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 35(2019)
• Page Start: 12091
• Page End: 12095
• Publication Date: 2019-07-30
• Subjects: biological activity -- biosynthesis -- Bipolaris sp. TJ403-B1 -- sesterterpenes -- structure elucidation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201905966
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Bipolarolides A–G (1 –7 ), seven novel ophiobolin‐derived sesterterpenes with three new types of skeletons, were characterized from fungus Bipolaris sp. TJ403‐B1. Their structures were determined via spectroscopic analyses, X‐ray crystallography, and quantum chemical 13 C NMR and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 were uniquely defined by a multicyclic caged oxapentacyclo[9.3.0.0 1, 6 .0 5, 9 .1 8, 12 ]pentadecane‐bridged system. Compounds 3 and 4 featured an unprecedented 5‐5‐5‐5‐fused core skeleton, while 3 also contained an unexpected C‐3–C‐14 oxygen bridge to construct the caged architecture. Compounds 5 –7 form a new class of highly modified pentacyclic oxaspiro[4.4]nonane‐containing sesterterpene‐alkaloid hybrids. Their biosynthetic pathways and potential HMG‐CoA reductase inhibitory and antimicrobial activities are also discussed. Abstract : The discovery of seven ophiobolin‐derived sesterterpenes, bipolarolides A–G (1 –7 ), from the fungus Bipolaris sp. TJ403‐B1 adds three new classes to the ophiobolin sesterterpene family, represented by 1, 3, and 6 . Based on a reverse virtual screening and in vitro enzyme‐based validation, 1 was found to be a HMG‐CoA reductase inhibitor. Moreover, 6 showed significant antimicrobial activity against Candida albicans .