Cohaerins G-K, azaphilone pigments from Annulohypoxylon cohaerens and absolute stereochemistry of cohaerins C-K

Abstract

Four azaphilones, for which the trivial names cohaerins G, H, I and K are proposed, were isolated from the methanolic stromatal extract of Annulohypoxylon cohaerens together with the known metabolites cohaerins C-F and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl (BNT). Their planar structures were determined by NMR spectroscopy and by mass spectrometry. While their core structure is identical with cohaerin C and F, respectively, subgroups 2-hydroxy-6-methylphenyl and (1R,2R,4S)-4-hydroxy-2-methyl-6-oxocyclohexyl account for the structural diversity as substituents at C-3 of the azaphilone core. The absolute stereochemistry was assigned by NOE NMR experiments, CD spectroscopy and derivatisation with Mosher's acid; in addition, the stereochemistry of cohaerins C-F was revised. The metabolites showed cytotoxic effects besides a weak antimicrobial activity.

Keywords: Annulohypoxylon cohaerens; Azaphilone; Chemotaxonomy; Cohaerin; Natural products; Secondary metabolites; Structure elucidation; Xylariaceae.