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Chemical studies of metabolites from Pacific Ocean marine sponges and the starfish Dermasterias imbricata

University of British Columbia

A study of biologically active extracts of several Pacific Ocean marine sponges has led to the isolation of eight new and nine previously known natural products. The structures of the compounds were determined by a combination of spectroscopic data analysis and chemical interconversions. In addition, the partial synthesis of imbricatine (3), a cytotoxic metabolite of the starfish Dermasterias imbricata, was accomplished. Crude extracts from the sponge Petrosia contignata collected in Papua New Guinea showed potent cytotoxicity against the murine leukemia L1210 cell line. These extracts yielded contignasterol (24), a new highly oxygenated steroid that inhibited histamine release from rat peritoneal mast cells with an IC50 of 0.8 gM, and petrolactone (37), a new sesquiterpene with the drimane carbon skeleton. The structure of contignasterol, which contains the "unnatural" 1413 proton configuration and a cyclichemiacetal functionality in its side chain, was elucidated via spectroscopic studies of its tetraacetate and its reduction product penta acetate. A known polybrominated diphenylether 41 accounted for the cytotoxicity of the crude extracts. The sponge Acanthella sp. yielded ten sesquiterpenes, four of which were new. Compounds 80-87, 89 and 90 contained isonitrile, isothiocyanate, formamide, carbamate and chloride functional groups. In addition, violacene (88), a halogenated monoterpene previously isolated from the red algae Plocamium violaceum, was isolated from the sponge extracts. The Northeastern Pacific sponge Neoesperiopsis digitata yielded neoesperlactone (96), an eighteen carbon fatty acid derived y-lactone. In addition, the major aromatic component was found to be identical by tic and 1H NMR comparison to commercially obtained p-hydroxybenzaldehyde. The study of the Papua New Guinea sponge Pseudaxinella massa led to the identification of a novel cyclic heptapeptide pseudaxinellin (103) which contained standard protein amino acid residues with the L configuration. The study of two species of marine sponges, Ptilocaulis trachys and Amphimedon sp. , collected at Enewetak lagoon, led to the isolation and identification of the depsipeptide majusculamide C (104)which had previously been found in the blue green alga Lyngbya majuscula collected at Enewetak. The synthetic confirmation of the tetrahydroisoquinoline substructure of the starfish metabolite imbricatine (3) was accomplished using a Pictet-Spengler reaction to couple the starting materials 3-(3,5-dihydroxyphenyl) alanine methyl ester (143) and sodium 3-(4-benzyloxyphenyl) glycidate (141). A series of deprotections and protections on the resulting racemic benzyltetrahydroisoquinoline led to a product 140 that was identical by 1H NMR and mass spectroscopic analysis to the protected Raney nickel reduction product of imbricatine (3).

Thesis/Dissertation

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2008-09-18

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http://hdl.handle.net/2429/2251

Chemistry

University of British Columbia

UBCV

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