Carneic Acids A and B, Chemotaxonomically Significant Antimicrobial Agents from the Xylariaceous Ascomycete Hypoxylon carneum (original) (raw)

2006, Journal of Natural Products

Carneic acids A and B (1, 2) are polyketide antibiotics structurally related to phomopsidin. They were isolated as major constituents of the stromata of Hypoxylon carneum, a species that had shown a highly specific secondary metabolite profile in a survey of xylariaceous ascomycetes based on HPLC profiling. Their chemical structures were elucidated by a combination of spectroscopic methods and by preparation of derivatives. An X-ray crystal structure of the dinitrobenzoate of carneic acid B methyl ester (8) was obtained, even allowing for determination of its absolute structure. The carneic acids showed weak antibacterial and moderate antifungal activities in the serial dilution assay against selected microbial organisms. They appear to be species-specific marker molecules in H. carneum from different geographic regions, but do not constitute major metabolites of more than 100 species of Xylariaceae. Their biological and chemotaxonomic significance is discussed. Hypoxylon carneum Petch (Xylariaceae, Figure 1) is a woodinhabiting ascomycete, first described from Sri Lanka 1 and later also reported from the United States, Venezuela, New Zealand, 2 and France. 3 It is one of the few species in the large genus Hypoxylon that is not restricted to certain geographic areas, but was proven to have a truly cosmopolitan distribution, being present in temperate as well as in subtropical and tropical climates. As judged from our field studies on its occurrence in southwestern France, 3 it is apparently not rare. Because of its morphological similarity to the common H. rubiginosum and other related species, it has probably been frequently overlooked. 3 The most striking feature to discriminate H. carneum from its relatives can be readily determined without any need for detailed microscopic studies: its pigments in KOH are faint purple, while those of related species yield dense orange, brown, or yellowish pigments in KOH. 3 Also, H. carneum has faintly yellowish granules beneath the stromata surface, whereas those of its allies are orange, red, or brown. These features are due to the presence of different secondary metabolites, which was established by a HPLC profiling study of about 2500 specimens and cultures of Hypoxylon and related Xylariaceae. 3-6 Recent evidence for the molecular taxonomy of Hypoxylon and allies 7 revealed that the closest affinities of H. carneum (i.e., the clades H1 and H2 as described in ref 7), as inferred from a molecular phylogenetic study, are with species that preferably contain azaphilones. These clades comprise, aside from some taxa that were not yet studied for HPLC profiles, for example, H. cercidicola, H. petriniae, 3 H. perforatum, H. pilgerianum, and H. rubiginosum. 3,4 H. carneum strongly differed from all of these species in its HPLC profile. The common stromatal azaphilone pigments of many Hypoxylon spp. of clades H1 and H2 as described in ref 7 (i.e., mitorubrins, rubiginosins, and hypomiltin 3,4) were not detected by HPLC-MS, and instead 4:5:4′:5′-tetrahydroxy-1:1′binaphthyl (BNT, 3) and a series of apparently species-specific but yet unknown metabolites were detected as major components. 4 Interestingly, only BNT (3) and daldinins, but no mitorubrin-type azaphilones, were also reported previously from the core species of another side branch of clade H1, i.e., H. fuscum.