Absolute configuration of polypropionate derivatives: Decempyrones A-J and their MptpA inhibition and anti-inflammatory activities

Under guidance of 1H NMR, ten new polypropionate derivatives, decempyrones A-J (1-10) along with two known analogues (11 and 12), were isolated from the marine-derived fungus Fusarium decemcellulare SYSUMS6716. The planar structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, and HR-ESIMS). The absolute configuration of the chiral centers in the side chain is a major obstacle for the structure identification of natural polypropionate derivatives. Herein, the J-based configurational analysis (JBCA), chemical degradation, geminal proton rule, and the modified Mosher's method were adopted to fix their absolute configurations in the side chain. Compounds 3 and 10 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide with IC50 values 22.4 +/- 1.8 and 21.7 +/- 1.1 mu M. In addition, compounds 3 and 10 displayed MptpA inhibitory activity with an IC50 value of 19.2 +/- 0.9 and 33.1 +/- 2.9 mu M. Structure-activity relationships of the polypropionate derivatives were discussed.