dibromophakellin and dibromophakellstatin

Oroidin derived, pyrrole imidazole marine alkaloids (PIAs) are attractive targets for synthetic organic chemists because of their structural complexity and diversity, as well as their interesting biological activities. A number of efforts have been carried out to develop strategies for the synthesis of these natural products. Members of PIAs (eg., 2-7), which contain tetracyclic ring systems possessing characteristic cyclic guanidine or urea moieties, show significant biological activities including anticancer activity and agonistic activity against the adrenoceptor. In this review, investigations of the total synthesis of the representative tetracyclic PIAs, dibromophakellin (2) and dibromophakellstatin (3), are described.

Topics: Alkaloids; Heterocyclic Compounds, 4 or More Rings; Imidazoles

We report herein that the oroidin-derived alkaloids palau'amine (1), dibromophakellin (2), and dibromophakellstatin (3) inhibit the proteolytic activity of the human 20S proteasome as well as the (i)20S immunoproteasome catalytic core. Palau'amine is found to prevent the degradation of ubiquitinylated proteins, including IκBα, in cell culture, which may be indicative of the potential mechanism by which these agents exhibit their exciting cytotoxic and immunosuppressive properties.

Topics: Alkaloids; Guanidines; HeLa Cells; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Microscopy, Confocal; NF-kappa B; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Pyrroles; Spiro Compounds; Stereoisomerism

A new method for the preparation of quaternary chiral aminals has been developed that employs an enamide-type Overman rearrangement process. This methodology was applied to enantioselective total syntheses of (+)-dibromophakellin and (+)-dibromophakellstatin.

Topics: Cyclization; Heterocyclic Compounds, 4 or More Rings; Hydroxyproline; Imidazoles; Stereoisomerism

Bioassay-guided isolation procedures using human tumor cell lines led to isolation of dibromophakellstatin (4) from the Republic of Seychelles sponge Phakellia mauritiana. The isolation, X-ray crystal structure elucidation, absolute stereochemistry, and antineoplastic activity have been summarized. P. mauritiana was also found to contain dibromophakellin (1), debromohymenialosine (2), thymidine, deoxyuridine, and thymine.

Topics: Animals; Antineoplastic Agents; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Imidazoles; Molecular Structure; Porifera; Tumor Cells, Cultured