Synthesis of Rhodomyrtone Analogs Modified at C7

Various analogs of rhodomyrtone with different acyl groups at C7 were prepared by selective chlorination of the core structure at C5 followed by a Duff formylation at C7. After protection of the phenolic OH groups, a sequence of Grignard reaction, oxidation, and deprotection led to the analogs. Some of them turned out to be very active.

Abstract

We developed a route to rhodomyrtone analogs that feature different acyl groups at C7. Since electrophilic substitution reactions on the aryl part of the rhodomyrtone core led to C5 derivatives, the C5 position was blocked by a chlorine. Subsequent Duff type formylation followed by Grignard addition to the aldehyde group and oxidation gave various phenones. The benzyl protecting groups were removed by hydrogenation or boron tribromide. Some derivatives turned out to be quite active against multiple resistant Staphylococcus aureus strains and a rhodomyrtone resistant mutant (Rom^R). The chlorine at C5 seems to have a beneficial effect on the antibacterial activity.

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