Chemical probes to probe the metabolism of fungicides

A study to elucidate a mechanism of fungicide resistance in Zymoseptoria tritici is reported. Resistance to the fenpropimorph has historically been ascribed to efflux of the fungicide. In Z. tritici, however, a metabolic resistance to fenpropimorph is observed that results in fungicide detoxification. In an effort to discover the potential cytochrome P450 enzymes responsible for this resistance, various chemical probes were synthesised and evaluated in relevant biological systems. Whilst the chemical probes were validated in rat liver microsomes, no evidence of cytochrome P450-mediated metabolism was found in Z. tritici. An initial strategy to synthesise the natural product cordigol was developed and is also reported. With this synthetic strategy, inspired by the group’s recently published synthesis of lophirone H, the core scaffold of cordigol could be constructed. The oxonium-Prins reaction used construct this core scaffold was found to be reversible and cis-selective by virtue of a previously unknown isomerisation. The scaffold was further functionalised and late stage intermediates were obtained. Therefore, the first total synthesis of cordigol appears to be within reach.Open Acces