Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge.

The isolation and structure determination of a new chlorinated benzophenone antibiotic, pestalone (1), is described. The new compound was produced by a cultured marine fungus only when a unicellular marine bacterium, strain CNJ-328, was co-cultured in the fungal fermentation. The fungus, isolated from the surface of the brown alga Rosenvingea sp. collected in the Bahamas Islands, was identified as an undescribed member of the genus Pestalotia. The structure of 1, initially assigned with only modest confidence by combined spectral and chemical data, was confirmed by single-crystal X-ray analysis. Pestalone (1) exhibits moderate in vitro cytotoxicity in the National Cancer Institute's 60 human tumor cell line screen (mean GI(50) = 6.0 microM). More importantly, pestalone shows potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium (MIC = 78 ng/mL), indicating that pestalone should be evaluated in advanced models of infectious disease.

New cytotoxic sterol glycosides from the octocoral Carijoa (Telesto) riisei.

Two new steroidal glycosides, 3beta-O-(3'-O-acetyl-beta-D-arabinopyranosyl)-25xi-choles tan e-3beta, 5alpha,6beta,26-tetrol-26-acetate (riisein A, 2) and 3beta-O-(4'-O-acetyl-beta-D-arabinopyranosyl)-25xi-choles tan e-3beta, 5alpha,6beta,26-tetrol-26-acetate (riisein B, 3), were isolated from extracts of the Brazilian telestacean octocoral Carijoa (Telesto) riisei collected near Rio de Janeiro. The new glycosides co-occur with the polyhydroxy sterol, 25xi-cholestane-3beta,5alpha,6beta, 26-tetrol-26-acetate (1), an inseparable diastereomeric mixture previously reported from Telesto riisei collected in Micronesia. The structures of the new glycosides were assigned by spectroscopic methods and by comparison with spectral data for sterol 1. Riiseins A and B showed in vitro cytotoxicity toward HCT-116 human colon adenocarcinoma with IC(50) values of 2.0 microg/mL.

Tamandarins A and B: new cytotoxic depsipeptides from a Brazilian ascidian of the family Didemnidae.

The structures of two new, naturally occurring cytotoxic depsipeptides, tamandarins A and B (1 and 2), are presented. The tamandarins were isolated from an unidentified Brazilian marine ascidian of the family Didemnidae. The structures of the new cytotoxins were assigned by interpretation of FABMS data and by extensive 2D NMR analyses. The absolute configurations of the tamandarins were assigned by acid and alkaline hydrolysis to yield their corresponding amino acids, which were then analyzed as their Marfey derivatives. The cytotoxicity of tamandarin A (1) was evaluated against various human cancer cell lines and shown to be slightly more potent than didemnin B. A qualitative discussion of the conformation of tamandarin A (1) in solution, obtained from NMR J-value data, variable temperature experiments, and NOESY/ROESY data, is included.

New fish feeding deterrents, including a novel sesquiterpenoid heterogorgiolide, from the brazilian gorgonian heterogorgia uatumani(Octocorallia, gorgonacea)

Studies of the Brazilian gorgonian octocoral Heterogorgia uatumani have resulted in the discovery of two metabolites that inhibit fish feeding under natural conditions. These are the previously reported eunicellane diterpenoid, (6E)-2alpha,9alpha-epoxyeunicella-6, 11(12)-dien-3beta-ol (1) and a new sesquiterpene lactone, heterogorgiolide (2). The structures of 1 and 2 were determined by spectroscopic methods and by comparison of spectral data with literature values. Field bioassays of the two compounds, at their natural concentrations, confirmed that they deter predation by a complex assemblage of reef fishes. This is an unusual observation showing that defenses are derived from both sesqui- and diterpenoid metabolites.

Brasilenyne and cis-dihydrorhodophytin: Antifeedant medium-ring haloethers from a sea hare (Aplysia brasiliana).

Two straight-chain C(15) fish antifeedants have been isolated from the sea hare Aplysia brasiliana. Chemical, spectral, and x-ray diffraction studies led to the characterization of these medium-ring ethers as brasilenyne (2) and cis-dihydrorhodophytin (3). The oxonin ring system of 2 is novel in nature. Biosynthetic considerations permit the postulation that a third compound, a noncrystalline congener of these compounds, is cis-isodihydrohodophytin (4).