(+)/(−)-Mycosphatide A, a pair of highly oxidized polyketides with lipid-lowering activity from the mangrove endophytic fungus Mycosphaerella sp. SYSU-DZG01

Abstract

(±)-Mycosphatide A (1a/1b), a pair of highly oxidized enantiomeric polyketides featuring a unique 5/5/6/5-fused tetracyclic ring system, were isolated from the mangrove endophytic fungus Mycosphaerella sp. SYSU-DZG01. Their structures were established by extensive spectroscopic analyses, single crystal X-ray diffraction, and experimental electronic circular dichroism (ECD) spectra comparison. The plausible biosynthetic pathway of 1 was proposed, which involved the generation of a key spiro[4.5]decane scaffold. Compounds (+)-1a and (−)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model, with EC50 values of 7.85 ± 1.56 and 8.87 ± 0.80 µmol/L, respectively.