Polygodial

Abstract: Chemical investigation of antifeedant compounds from Warburgia plants has led to the isolation and characterization of polygodial, ugandensidial, and the unknown warburganal, which exhibit very strong antifeedant activity against the African army worm.

Abstract: A series of sesquiterpene dialdehydes was isolated from the East African medicinal plants Warburgia stuhlmannii and Warburgia ugandensis (Canellaceae) as antibiotics, particularly against Saccharomyces cerevisiae, Candida utilis, and Sclerotinia libertiana. Among these sesquiterpene dialdehydes, polygodial [1] exhibited the most potent activity. When tested on S. cerevisiae, polygodial proved to be fungicidal rather than fungistatic. When the cells of S. cerevisiae are treated in vitro with polygodial for 10 min, the cell membrane becomes severely damaged, and many vesicles, possibly formed from the fragmented cell membrane, can be observed within the cytoplasm. The observation of cell membrane lesions led us to propose a rather innovative hypothesis: the use of polygodial to facilitate the transmembrane transport of exogenous chemicals into cells. For example, polygodial could be combined with an antibiotic having poor cell membrane permeability in an effort to increase its antibiotic activity by increasing its ability to gain entrance into the cell. We report here that a remarkably enhanced efficacy was obtained when actinomycin D was used in combination with polygodial. We believe polygodial may be acting as an "advance scout," punching holes in the plasma membrane and gaining an entrance into the cell for an antibiotic previously less effective because of problems with cell membrane permeability.

Abstract: The stereospecific preparation of various 1-vinyl-2,6,6-trimethylcyclohex-1-enes (6) as potential diene precursors in the Diels–Alder reaction with dimethyl acetylenedicarboxylate have been investigated. The reaction of the parent diene (6a) with dimethyl acetylenedicarboxylate affords an adduct (18) in 94% yield. This species was reductively isomerised using 10% Pd/C/H2 and a mineral acid to give a trans-fused decalin diester (19). Reduction of (19) with lithium aluminium hydride afforded 1,4,4a,5,6,8,8a-octahydro-5,8,8a-trimethyl-1 β,4a α,8aβ-naphthalene-1,2-dimethanol (24) a key starting material for the highly efficient syntheses of five drimane sesquiterpene natural products, cinnamolide (1), polygodial (2), isodrimeninol (3), drimenin (4), and warburganal (5). Microbial oxidation reactions using C. elegans or A. niger of (2), (24), and (1) gave good yields of the corresponding 3β-hydroxy derivatives, (30), (31), and (32). Several other unusually substituted drimane derivatives are reported.

Abstract: Twenty unsaturated sesquiterpene dialdehydes were tested for antimicrobial, algaecidal, cytotoxic, and mutagenic activity. In addition to the known antifungal activity, polygodial (1) also exhibited antibacterial and cytotoxic activity; epipolygodial (2) was slightly less active. The most active compounds were: isovelleral (7), isoisovelleral (8), velleral (20), and methylmarasmate (6). With the exception of velleral (20), they also exhibited mutagenic activity in the Salmonella/microsome assay. Derivatization to less polar compounds usually increased the antimicrobial and cytotoxic effects and reduced mutagenicity, while the introduction of hydroxyl groups had the reverse effect.