Ochrathinols A and B, two pairs of sulfur-containing racemates from an Antarctic fungus Aspergillus ochraceopetaliformis SCSIO 05702 inhibit LPS-induced pro-inflammatory cytokines and NO production

Ochrathinols A and B ((±)-1 and (±)-2), two undescribed sulfur-containing racemates, and ochracids A and B (3 and 4), two unprecedented pyrrolizidine alkaloids, were isolated from an Antarctic soil-derived fungus Aspergillus ochraceopetaliformis SCSIO 05702. Their structures including absolute configurations were determined through extensive spectroscopic analysis, chiral-phase HPLC analysis, quantum ECD calculations, and X-ray single-crystal diffraction. Ochrathinols A and B are unprecedented sulfur natural products featuring a novel 3-methylhexahydro-2H-cyclopenta [b]thiophene core. Interestingly, ochrathinol A ((±)-1) outstandingly suppressed the release of LPS-induced IL-1β, IL-6, and TNF-α inflammatory cytokines with concentration of 10 μM and alleviated the unbalanced NAD+/NADH ratio caused by LPS in RAW264.7 macrophages. [Display omitted] •Ochrathinols A and B ((±)-1 and (±)-2) were isolated from an Antarctic fungus.•Ochrathinols A and B are unprecedented sulfur natural products featuring a novel 3-methylhexahydro-2H-cyclopenta [b]thiophene core.•Their absolute configurations were elucidated by ECD calculations and X-ray single-crystal diffraction.•Ochrathinol A ((±)-1) exhibited potent anti-inflammatory activity.