Secondary fungal metabolites and their biological activities, IV. Synthesis of compounds with structural similarities to the toxic metabolites of the pathogenic fungus Heterobasidion annosum and investigation of their antibiotic activities.
A series of synthetic analogues of fomannoxin and fomajorin S, the toxic metabolites of the basidiomycete Heterobasidion annosum, was prepared in order to investigate which partial structures of the molecules are responsible for their biological activities. Of the compounds synthesized the five indane-2-acid derivatives 5-acetylindane-2-carboxylic acid (2), (+/-)5-formylindane-2-carboxylic acid (3), (+/-)indane-2,5-dicarboxylic acid (4), (+/-)formyl-2-methylindane-2-carboxylic acid (7) and 5-acetyl-indane-2,2-dicarboxylic acid (10) and 4-(2'-ethylbutyloxy)benzaldehyde (18) have not yet been described. Different biological test systems were employed to investigate the antibiotic activities of the synthesized analogues. The experimental results suggest that in the case of fomajorin S, the structural element essential for its toxicity is the 2-H- or 2-methylindane 2-acid. From the results obtained with the synthetic analogues of fomannoxin, it is now evident that the toxicity of this fungal metabolite can be attributed to an aromatic ring with a carbonyl or carboxyl substituent combined with a branched lipophilic side chain in p-substitution.
Sonnenbichler
J
J
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Dietrich
J
J
Schäfer
W
W
Zetl
I
I
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001487:Basidiomycota / Q000378:metabolism*; D001572:Benzofurans / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003198:Computer Simulation; D003470:Culture Media; D007189:Indans / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D001572:Benzofurans; D003470:Culture Media; D007189:Indans; C084141:fomannoxin; C085531:fomajorin S