A new tyrosine kinase inhibitor from a marine isolate of Ulocladium botrytis and new metabolites from the marine fungi Asteromyces cruciatus and Varicosporina ramulosa

The sponge-derived fungi Ulocladium botrytis and Asteromyces cruciatus, and the algal-derived fungus Varicosporina ramulosa, were isolated and extract s from cultures investigated for their metabolite production. Investigation s of the extract of the culture of U. botrytis guided by bioassay yielded t he new tyrosine kinase (p56(1ck)) inhibitor ulocladol (1) together with 1-h ydroxy-6-methyl-8-(hydroxymethyl)xanthone (3), which showed antifungal acti vity. The extract of the culture medium of A. cruciatus yielded the new met abolite (+)-2,4-dimethyl-4,5-dihydrofuran-3-carbaldehyde (4) together with the known compounds (3S,5R)-dimethyldihydrofuran-2-one (5) and tri-O-acetyl glycerol. From V. ramulosa the five macrodiolides grahamimycin A(1) (6), c olletoketol (7), (6R,11R,12R,14R)-colletodiol (8), 9,10-dihydro-(6R,11S,12S ,14R)-colletodiol (9) and 9,10-dihydro-(6R,11R,12R,14R)-colletodiol (10) to gether with ergosterol were obtained, 9 and 10 being new fungal metabolites .