Trichophycins B-F, Chlorovinylidene-Containing Polyketides Isolated from a Cyanobacterial Bloom

NMR-guided isolation (based on 1D H-1 and C-13 NMR resonances consistent with a chlorovinylidene moiety) resulted in the characterization of five new highly functionalized polyketides, trichophycins B-F (1-5), and one nonchlorinated metabolite tricholactone (6) from a collection of Trichodesmium bloom material from the Gulf of Mexico. The planar structures of 1-6 were determined using 1D and 2D NMR spectroscopy, mass spectrometry, and complementary spectroscopic procedures. Absolute configuration analysis of 1 and 2 were carried out by H-1 NMR analysis of diastereomeric Mosher esters in addition to ECD spectroscopy, J-based configuration analysis, and DFT calculations. The absolute configurations of 3-6 were proposed on the basis of comparative analysis of C-13 NMR chemical shifts, relative configurations, and optical rotation values to compounds 1 and 2. Compounds 1-5 represent new additions to the trichophycin family and are hallmarked by a chlorovinylidene moiety. These new trichophycins and tricholactone (1-6) feature intriguing variations with respect to putative biosynthetic starting units, halogenation, and terminations, and trichophycin E (4) features a rare alkynyl bromide functionality. The phenyl-containing trichophycins showed low cytotoxicity to neuro-2A cells, while the alkyne-containing trichophycins showed no toxicity.