On June 29, 2019 Professor Yonghui Zhang and his team published their latest achievements of sesterterpenes named “Bipolarolides A–G, Ophiobolin-Derived Sesterterpenes Representing Three New Carbon Skeletons from Bipolaris sp. TJ403-B1. (Angew. Chem. Int. Ed., doi: 10.1002/anie.201905966)” in top international chemistry journal Angewandte Chemie International Edition. Professor Zhang and ZhengXi Hu from School of pharmacy are corresponding authors of the study.

 Terpenes have always attracted considerable attention in the field of natural products chemistry because of their complex frameworks and intriguing biological properties. Taxol, artemisinin, andrographolide and other famous drug molecules are terpenes. Team led by Professor Zhang has achieved groundbreaking findings on terpenes in recent years (Angew. Chem. Int. Ed. 2016, 55, 4069; Chem. Sci. 2016, 7, 6563−6572; Org. Lett. 2018, 20, 5198−5202).

Terpenes can be divided into hemiterpene, sesquiterpenoids, diterpenoids, sesterterpenoids and triterpenoids based on the number of C₅ isoprene units in the molecular framework of compounds. Sesterterpenoids are composed of 5 C₅ units, which are relatively rare compared with the other terpenes such as sesquiterpenes (3 isoprene units; C₁₅), diterpenes (4 isoprene units; C₂₀), and triterpenes (6 isoprene units; C₃₀). Bipolarolides A–G (1–7), seven ophiobolin-derived sesterterpenes representing three new carbon skeletons, were characterized from Bipolaris sp. (TJ403-B1) by Professor Zhang and his team. Compound 1 and 2 were uniquely defined by a multicyclic caged oxapentacyclo [9.3.0.01,6.05,9.18,12] pentadecane bridged system; compound 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; compound 5 to 7 represented a new class of highly modified pentacyclic oxaspiro [4.4] nonane-containing sesterterpene-alkaloid hybrids. According to the results of structural based virtual screening and biological activity determination, compound 1 was found to be a potential HMGR antagonist with an IC₅₀ value of 2.46 ± 0.07 µM. Further study showed that compound 1 dose-dependently suppressed oleic acid-elicited lipid accumulation and significantly decreased the intracellular concentration of total cholesterol and triglyceride in HepG2 cells. Furthermore, compounds 1–9 were evaluated in terms of antimicrobial activity against drug-resistant microbial pathogens [ESBL-producing Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillinresistant Staphylococcus aureus (MRSA), Enterococcus faecalis] and the fungus Candida albicans, and 6 showed the highest antimicrobial activity against C. albicans, with an MIC value of 4 μg/mL. The study greatly expands the chemistry of known ophiobolintype scaffolds and furnish challenging targets for chemosynthesis as well as biosynthesis and elucidation of the fascinating mechanism.

Link:
https://onlinelibrary.wiley.com/doi/10.1002/anie.201905966（Angew. Chem. Int. Ed.）