WS-5995 C

[reaction: see text] Densely substituted styryl sulfone 20 is shown to undergo double annulation with phthalide 21 to give, in one-pot operation and in excellent yield, the benzonaphthopyranone scaffold 22 of gilvocarcins.

Intramolecular palladium-mediated arylation approaches to benzo[b]fluorenes have been investigated. The methodology has been applied in a short synthesis of tri-O-methylkinafluorenone, providing an effective alternative to Friedel-Crafts-based approaches. During the course of this work, an acid-promoted quinolactonization of naphthoquinones was also developed, providing direct access to either ortho or para isomers as desired. Application of this methodology in syntheses of the antibiotics WS-5995A, WS-5995C, and functional analogues was demonstrated, and antitumoral activity of this class was determined.

The mycorrhiza helper bacterium Streptomyces strain AcH 505 improves mycelial growth of ectomycorrhizal fungi and formation of ectomycorrhizas between Amanita muscaria and spruce but suppresses the growth of plant-pathogenic fungi, suggesting that it produces both fungal growth-stimulating and -suppressing compounds. The dominant fungal-growth-promoting substance produced by strain AcH 505, auxofuran, was isolated, and its effect on the levels of gene expression of A. muscaria was investigated. Auxofuran and its synthetic analogue 7-dehydroxy-auxofuran were most effective at a concentration of 15 microM, and application of these compounds led to increased lipid metabolism-related gene expression. Cocultivation of strain AcH 505 and A. muscaria stimulated auxofuran production by the streptomycete. The antifungal substances produced by strain AcH 505 were identified as the antibiotics WS-5995 B and C. WS-5995 B completely blocked mycelial growth at a concentration of 60 microM and caused a cell stress-related gene expression response in A. muscaria. Characterization of these compounds provides the foundation for molecular analysis of the fungus-bacterium interaction in the ectomycorrhizal symbiosis between fly agaric and spruce.