Stress-driven discovery of metabolites from the phytopathogenic fungus Leptosphaeria maculans: Structure and activity of leptomaculins A–E

A search for stress inducing metabolites produced by the plant pathogenic fungus Leptosphaeria maculans led to the isolation and structure elucidation of eight new metabolites, the leptomaculins and deacetylleptomaculins A–E. The chemical structures and absolute stereochemistry of the new metabolites were deduced by detailed analysis of 1D and 2D NMR spectroscopic data and chemical degradation of the toxin sirodesmin PL. Leptomaculins A and B are the first examples of naturally occurring 2,3-oxopiperazinethione and 2,3-dioxopiperazine, respectively. Stress inducing activity was found in the fungal phytotoxins sirodesmin PL and deacetylsirodesmin PL but not in any of the new leptomaculins, phomalide or phomamide. A metabolic pathway for biosynthesis of the first 2,3-(di)oxopiperazine(thione) from sirodesmin PL is proposed.

The chemical structures of the first natural 2,3-oxopiperazinethione and 2,3-dioxopiperazine, leptomaculins A and B, together with six new leptomaculins as well as biological activities and proposed biosynthetic pathways are reported.Figure optionsDownload as PowerPoint slide