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In this first report on the chemistry of the sponge Stylissa caribica, two known bromopyrrole metabolites and a new compound, N-methyldibromoisophakellin (1), were isolated and identified. The structure of 1 was determined using spectroscopic methods and the computer program COCON. N-Methyldibromoisophakellin (1) was shown to be the only secondary metabolite in Stylissa caribica that, at its natural concentration, is active as a feeding deterrent against a common omnivorous reef fish.In a recent survey of the chemical antipredatory defenses of 71 species of Caribbean sponges, it was discovered that all of the five species within the family Axinellidae yielded crude organic extracts that deterred the feeding of predatory reef fish in aquarium assays. 1 More recently it has been shown that one species, Axinella corrugata (previously Teichaxinella morchella), yielded high concentrations of stevensine as the single compound responsible for feeding deterrency. 2 The purpose of the study reported herein was to isolate and identify the metabolite(s) responsible for the chemical defense of Stylissa caribica, a sponge closely related to A. corrugata. To the best of our knowledge, this is the first report on the chemistry of S. caribica.A series of brominated pyrrole alkaloids have been isolated from a specimen of the sponge S. caribica collected off the coast of Sweetings Cay, Bahamas. Bioassay-guided fractionation of the methanol extract of this sponge resulted in the isolation of two known bromopyrrole-derived alkaloids, dibromoisophakellin (2, 13 mg) and ageliferin (3, 3 mg), as well as the new compound N-methyldibromoisophakellin (1, 140 mg). We describe herein the isolation, structural elucidation, and antifeedant properties against the common predatory reef fish Thalassoma bifasciatum of the new bromopyrrole alkaloid 1.The compounds 1-3 could be isolated using previously reported methods (details see Experimental Section and Supporting Information). The brominated alkaloids dibromoisophakellin (2) and ageliferin (3) Table 1). By comparison of δ C of 1 with all known intramolecular cyclized oroidin derivatives, the isophakellin skeleton was obtained. 4 Therefore, the structure of 1 was identified and confirmed by COCON 5 as the N-methyl derivative of dibromoisophakellin (2). The absolute configuration of 1 was determined by comparison of the optical rotation of 1 with that of 2. 3a Since recent studies 6 have found no evidence for structural or nutritional defenses, deterrent metabolites appear to be the principal defensive strategy of Caribbean sponges against predatory reef fishes. To investigate the feeding deterrency of the major metabolite of S. caribica, aquarium assays were performed using previously reported methods. 7 When incorporated into artificial foods at the same volumetric concentration as found in sponge tissue (0.9 mg/mL), N-methyldibromoisophakellin (1) deterred

The chemistry of the burrowing sponge Aka coralliphagum was investigated to identify chemically labile secondary metabolites. The HPLC-MS analysis of the two growth forms typica and incrustans revealed different metabolites. The previously unknown sulfated compounds siphonodictyals B1 to B3 (6-8), corallidictyals C (9) and D (10), and siphonodictyal G (11) were isolated, and their structures were elucidated by NMR and MS experiments. The compounds were tested in a DPPH assay, in antimicrobial assays against bacteria, yeasts, and fungi, and in antiproliferation assays using cultures of mouse fibroblasts. The biological activity was linked to the presence of the ortho-hydroquinone moiety.The burrowing sponge Aka coralliphagum ()Siphonodictyon coralliphagum) is a bright yellow colored sponge that burrows into corals. Four distinct morphological growth forms have been described for Aka coralliphagum from the Caribbean: forma typica, f. tubulosa, f. obruta, and f. incrustans. 1 Several bioactive sesquiterpene hydroquinones, such as the siphonodictyals (B, 1) and siphonodictyols, 2 were obtained from the forms tubulosa and typica. Although the isolation of labile compounds such as siphonodictyols G (2) and H (3) suggested the existence of additional sulfated phenolic compounds in A. coralliphagum, compounds such as the siphonodictyals were isolated without respect to the occurrence of sulfated metabolites. Past isolation and purification methods did not account for the problem of compound hydrolysis. 2a,b This paper describes the isolation, structure elucidation, and biological testing of the new, labile metabolites siphonodictyals B1 to B3 (6-8), corallidictyals C (9) and D (10), and siphonodictyal G (11) from the Aka growth form incrustans. In order to compare the secondary metabolites of the two growth forms incrustans and typica, an HPLC analysis of their crude extracts was performed. These two forms of Aka occur in different habitats, with typica predominating on shallow water reefs (10-15 m) while incrustans occurs on deep water vertical slopes (20-25 m). It was deemed important to isolate the labile natural products of these two growth forms in their naturally occurring forms in order to understand more about their biological and ecological function. Results and DiscussionExtracts of sponge samples were investigated by an HPLC-MS screening. The two growth forms of Aka coralliphagum (typica and incrustans) showed differences in HPLC fingerprints and their major metabolites (Figure 1). While forma typica contained more polar compounds (shorter retention times), forma incrustans contained three main compounds with a less polar character. Further characterization by HPLC-API-CID-MS/MS showed a single or double sulfation of compounds with shorter retention times. This was deduced by loss of m/z 80 under MS/MS conditions and detection of a [SO 3 ] -ion at m/z 80 (see Supporting Information) 3 as well as a sulfur-specific isotopic pattern. These results indicate that the two growth forms have considerable differences...

Bromophenols are present in polychaetes as well as in algae in marine environments including the North Sea. They are thought to cause the typical sea-like taste and flavour. The ecological function of brominated phenols is not clear yet, but they may play a role in chemical defence and deterrence [Kicklighter, C.E., Kubaneck, J., Hay, M.E., 2004. Do brominated natural products defend marine worms from consumers? Some do, most don't. Limnol. Oceanogr. 49,[430][431][432][433][434][435][436][437][438][439][440][441]. Some brominated phenols are commercially used as industrial flame retardants as, e.g., 2,4,6-tribromophenol and are suspected to disrupt the humoral system by showing tyroid hormone-like activity [Legler, I., Brouwer, A., 2003. Are brominated flame retardants endocrine disruptors? Environ. Int. 29,[879][880][881][882][883][884][885]. In this study 2-bromophenol (2-BP), 4-bromophenol (4-BP), 2,4-dibromophenol (2,4-DBP), 2,6-dibromophenol (2,6-DBP) and 2,4,6-tribromophenol (2,4,6-TBP), all of which are present in marine organisms, were tested. Especially 2,4-DBP and 2,4,6-TBP showed a significant effect on the Ca 2+ homeostasis in endocrine cells (PC 12). The reduction of depolarization induced Ca 2+ elevations by 2,4-DBP and 2,4,6-TBP and the increase of intracellular Ca 2+ by both substances, partly released from intracellular stores, may suggest a link to the disrupting effect of endocrine systems by brominated phenols. 2,4-DBP was the most potent substance we tested in respect to inhibition of voltage dependent Ca 2+ currents as revealed in whole cell patch clamp experiments. Brominated phenols disturb cellular Ca 2+ signaling with differential efficacy, depending on the number and position of bromine.