Immunomodulatory Polyketides from a Phoma-like Fungus Isolated from a Soft Coral

Fourteen new polyketides with a trans-fused decalin ring system, libertalides A-N (3-16), together with two known analogues, aspermytin A and its acetate (1, 2), were isolated from the fermentation extract of a coral-derived Libertasomyces sp. fungus. Their relative configurations were elucidated on the basis of detailed spectroscopic analysis, and the absolute configurations were determined by TDDFT-ECD and optical rotation (OR) calculations. The OR of 1 and 2 were found to have opposite signs in CH₃CN and CHCl₃, which was in agreement with the OR calculations producing alternating signs for the optical rotation depending on the applied conditions. Because the signs of the OR for 1 and 2 showed high solvent dependence, they may not be used alone to correlate the absolute configurations. Compound 16 displayed structural novelty characterized by an α-enol ether bridge conjugated with an aldehyde group. In in vitro immunomodulatory screening, compounds 1, 4, and 10 significantly induced the proliferation of CD3⁺ T cells, while compounds 2, 7, 11, and 14 significantly increased the CD4⁺/CD8⁺ ratio at 3 μM. A preliminary structure-activity analysis revealed a crucial role of Δ⁷ and a terminal OH group in the regulation of CD3⁺ T cell proliferation. This is the first report of immunoregulatory activity for metabolites of this kind.