Isolation of new compounds related to xyloketals biosynthesis implies an alternative pathway for furan-fused-chromene formation

Abstract

In fungi, there is a rare group of natural products harboring the 2,3,3a,9a-tetrahydro-4H-furo[2,3-b]chromene skeleton, represented by xyloketal B, which display a wide range of biological activities and have drawn significant attention. In this work, four new analogues simpliketals A–D (1–4), as well as two other new compounds simplilactones A and B (5 and 6), were isolated from Simplicillium sp. AHK071-01. Their structures were elucidated by extensive NMR spectroscopic methods, ¹³C NMR calculation, single-crystal X-ray diffraction, and ECD calculation. In addition, five known compounds (7–11) including alboatrin (7) were also obtained. Based on the structural similarity of the above compounds, we inferred that compounds 5, 6, and 8–11 might be biosynthetically related with 1–4 and 7, which allowed us to propose an alternative biosynthetic route to generate the furan-fused chromene skeleton of this class of compounds, instead of a previously presumed polyketide–terpenoid hybrid pathway. Finally, cytotoxicity assays showed that 1–4 exhibited weak inhibitory activity on PANC-1 cells and that 2 and 3 possessed moderate activity against SH-SY5Y cells.