New Hybrid Phenalenone Dimer, Highly Conjugated Dihydroxylated C Steroid and Azaphilone from the Culture Extract of a Marine Sponge-Associated Fungus, KUFA 1767.

An undescribed hybrid phenalenone dimer, talaropinophilone (), an unreported azaphilone, 7--pinazaphilone B (), an unreported phthalide dimer, talaropinophilide (), and an undescribed 9,15-dihydroxy-ergosta-4,6,8 (14)-tetraen-3-one () were isolated together with the previously reported bacillisporins A () and B (), an azaphilone derivative, Sch 1385568 (), 1-deoxyrubralactone (), acetylquestinol (), piniterpenoid D () and 3,5-dihydroxy-4-methylphthalaldehydic acid () from the ethyl acetate extract of the culture of a marine sponge-derived fungus, KUFA 1767. The structures of the undescribed compounds were elucidated by 1D and 2D NMR as well as high-resolution mass spectral analyses. The absolute configuration of C-9' of and was revised to be 9' using the coupling constant value between C-8' and C-9' and was confirmed by ROESY correlations in the case of . The absolute configurations of the stereogenic carbons in and were established by X-ray crystallographic analysis. Compounds ,, -, and were tested for antibacterial activity against four reference strains, viz. two Gram-positive ( ATCC 29213, ATCC 29212) and two Gram-negative ( ATCC 25922, ATCC 27853), as well as three multidrug-resistant strains, viz. an extended-spectrum β-lactamase (ESBL)-producing , a methicillin-resistant (MRSA) and a vancomycin-resistant (VRE). However, only and exhibited significant antibacterial activity against both ATCC 29213 and MRSA. Moreover, and also significantly inhibited biofilm formation in ATCC 29213 at both MIC and 2xMIC concentrations.