Brocaeloids A-C, 4-Oxoquinoline and Indole Alkaloids with C-2 Reversed Prenylation from the Mangrove-Derived Endophytic Fungus Penicillium brocae

Three new alkaloids, brocaeloids A-C (1-3), containing C-2 reversed prenylation, were isolated from cultures of Penicillium brocae MA-192, an endophytic fungus obtained from the fresh leaves of the marine mangrove plant Avicennia marina. Their structures were determined on the basis of 1D and 2D NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configuration of brocaeloid A (1) was established by gas-phase and solution conformational analysis and TDDFT-ECD calculations, which revealed that the fused hetero-ring adopted M-helicity conformation with axial orientation of the C-2 and C-3 substituents. The correct assignment of the hetero-ring conformation was found to be crucial in determining the relative and absolute configuration. Based on ECD calculations, the helicity of the 2,3-dihydroquinoline-4(1H)-one chromophore was correlated with the characteristic ECD transitions, and the resultant helicity rule was found to coincide with that of the chroman-4-one chromophore. X-ray single-crystal analysis of 1 by Cu-K-alpha radiation also confirmed the result of the stereochemical analysis obtained from ECD calculations. Brocaeloid B (2) showed lethality against brine shrimp (Artemia salina) with an LD50 value of 36.7 mu M.