Diketopiperazine and isoindolinone alkaloids from the endophytic fungus Aspergillus sp. HAB10R12

Four previously undescribed alkaloids, aspergillinine A–D, and four known diterpene pyrones were isolated from the potato dextrose agar (PDA) culture of Aspergillus sp. HAB10R12. The chemical structures of the isolated compounds were elucidated based on a detailed analysis of their NMR and MS data. The absolute configuration of the isolated compounds was determined by Electronic Circular Dichroism analysis coupled with computational methods. Aspergillinine A represents the first example of a diketopiperazine dipeptide containing the unnatural amino acid N-methyl kynurenine. Its absolute configuration revealed that it adopts a rather unusual conformation. Aspergillinine B represents a previously unencountered skeleton containing an isoindolinone ring. Aspergillinine C and D were similar to previously isolated diketopiperazine alkaloids, namely, lumpidin and brevianamide F, respectively. The diterpene pyrones were isolated twice previously, once from a soil-derived Aspergillus species, and once from the liquid culture of Aspergillus sp. HAB10R12. The alkaloids isolated in this study showed no antiproliferative activity when tested against HepG2 and A549 cancer cell lines. [Display omitted] •Four previously undescribed alkaloids were isolated from endophytic fungus (Aspergillus sp.)•Aspergillinine A is the first N-methyl kynurenine containing diketopiperazine.•Aspergillinine B possesses a previously undescribed isoindolinone skeleton.•Aspergillinine A adopts an unusual conformation as deduced from NMR and confirmed by DFT calculations.