Synthesis of four novel natural product inspired scaffolds for drug discovery.

Inspired by the novel spiro structures of a number of bioactive natural products such as the histrionicotoxins, a series of novel spiro scaffolds have been designed and robust syntheses developed. The scaffolds are ready-to-use building blocks and can be easily prepared on a 5-20 g scale. They contain two amino groups (one Boc-protected) and have been designed for ease of conversion to a lead generation library, using either amide formation or reductive amination procedures.

Ianthesine E, a new bromotyrosine-derived metabolite from the Great Barrier Reef sponge Pseudoceratina sp.

The new compound ianthesine E (1) was isolated from the Great Barrier Reef marine sponge Pseudoceratina sp. along with the known metabolites 11-hydroxyaerothionin (2), aerothionin (3) and 11,19-dideoxyfistularin 3 (4). Structures were determined on the basis of their spectroscopic data.

Exiguaquinol: a novel pentacyclic hydroquinone from Neopetrosia exigua that inhibits Helicobacter pylori MurI.

Bioassay-guided fractionation of the methanol extract of the Australian sponge Neopetrosia exigua led to the isolation of exiguaquinol (2), a new pentacyclic hydroquinone that inhibited Helicobacter pylori glutamate racemase (MurI) with an IC(50) of 4.4 microM. Its structure and relative configuration were assigned on the basis of spectroscopic data.

Dysinosin A: a novel inhibitor of Factor VIIa and thrombin from a new genus and species of Australian sponge of the family Dysideidae.

A new marine natural product dysinosin A 1 has been isolated from a new genus and species of sponge of the family Dysideidae found near Lizard Island, North Queensland, Australia. Dysinosin A is a potent inhibitor of the blood coagulation cascade factor VIIa and an inhibitor of the serine protease thrombin. Among the distinctive features of dysinosin A are the presence of a 5,6-dihydroxy-octahydroindole-2-carboxylic acid, 3-amino-ethyl 1-N-amidino-Delta-3-pyrroline, a sulfated glyceric acid, and d-leucine, assembled through three peptidic linkages.

Adociasulfates 1, 7, and 8: New Bioactive Hexaprenoid Hydroquinones from the Marine Sponge Adocia sp.

Adociasulfate 1 (1), adociasulfate 7 (2), and adociasulfate 8 (3), which are inhibitors of proton pump activity in hen bone-derived membrane vesicles, were isolated from an extract of the sponge Adocia sp. (Chalinidae). Structure elucidation by 2D-NMR spectroscopy revealed that they are novel hexaprenoid hydroquinone sulfates.

Axinellamines A-D, Novel Imidazo-Azolo-Imidazole Alkaloids from the Australian Marine Sponge Axinella sp.

Four imidazo-azolo-imidazole alkaloids, axinellamines A-D, have been isolated from an Australian marine sponge, Axinella sp. (order: Halichondrida: family: Axinellidae). These compounds contain a unique perhydrocyclopenta-imidazo-azolo-imidazole carbon skeleton.