Leupyrrins are highly potent antifungal agents. As tructure-activity-relationship study of natural and synthetic derivatives is reported which reveals importanti nsights into the biological relevance of several structural subunits leading to the discovery of highly potent but drastically simplified leupylogs that incorporate as table and readily availablea romatic side chain. For their synthesis ac oncise strategy is described that enablesashort and versatile access.

The enantioselective total synthesis of (+)-salimabromide was accomplished by a concise two-step conversion of the fully functionalized dibromo-tetraline core, involving a one-pot Baeyer–Villiger/allylic oxidation by an innovative radical reagent combination. This route unequivocally resolves the stereochemistry and reveals the highly unusual, almost racemic nature of natural salimabromide.

What prompted you to investigate this topic? Leupyrrins exhibit very potent antifungal activities, antiproliferative, and anti-HIV properties. They efficiently inhibit DNA, RNA, and protein syntheses without disrupting other cellular systems. Nevertheless, its biological target as well as its pharmacophore is unknown yet. After the elucidation of the full stereochemistry of these complex macrodiolides and the total synthesis of leupyrrin A 1 and B 1 it was our intention to explore the molecular processes behind these fascinating secondary metabolites. An improved knowledge of the detailed mechanisms will help to evaluate practical applications in basic research, medicine, and agriculture.

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