Synthesis of Kendomycin and Elisapterosin B

Research project P 14729 Synthesis of Kendomycin and Elisapterosin B Johann MULZER 27.11.2000 The aim of the project is the stereoselective and efficient total synthesis of three novel natural products with unusual structures and a highly interesting biological profile. Kendomycin is a repeatedly discovered ansamycin which in contrast to the known ansamycins has a carba-ansachain spanned over a pbenzoquinoid core. The compound shows an extremely broad biospectrum ranging from antibiotic and cytotoxic to antiosteoporotic activity. Besides solving the stereoproblems the synthesis is intended to elucidate the biogenesis of the compound. Elisapterosin B and Elisabethin A are diterpenoids with novel structures which are discussed as potential antituberculosis agents. The synthesis is designed to procure the compounds which are not readily available from marine organisms. Another intention is the final confirmation of the structure which so far been assigned on the basis of NMR data only.

This project has aimed for total synthese of the two newly isolated natural products elisabethin A and kendomycin. Elisabethin A has been gained in small amounts from the Carribean seawhip pseudopterogorgia elisabethae, whereas kendomycin is a metabolite from streptomyces. Both compounds are attractive for the synthetic chemists because they combine novel structural architecture with interesting biological properties. Thus, elisabethin A is active against tubercolosis and has antiinflammatory properties, and kendomycin exhibits a broad antibacterial spectrum and inhibits osteoporosis. Therefore both compounds could serve as lead structures for novel drugs. In fact, soon after our group, other synthetic chemists in USA and Japan have started similar projects, and we were faced with an intensive worldwide competition throughout the duration of the project. However, as one can see from the publication and invitation list, we were more than able to stand our ground. The elisabethin A project is more or less finished, although we are still working on the optimization of the synthesis and the preparation of interesting structural analogs. The synthesis of kendomycin has not yet been completed, so that further efforts will be needed to reach our ultimate goal. However, we have access to sufficient quantities of advanced intermediates which have the entire carbon skeleton of the compound including the stereogenic centers.