Angewandte Chemie International Edition
© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
The cover picture shows schematically the 11-step synthesis of 6-epi-dysidiolide on a solid support. By means of this extraordinarily demanding and long solid-phase synthesis a small library of analogues of the Cdc25 protein phosphatase inhibitor dysidiolide was synthesized. This synthesis demonstrates that the solid-phase synthesis of natural products and compound libraries derived from them is feasible. This is a decisive cornerstone of a new principle for enhancing the efficiency of the hit- and lead-finding processes in pharmaceutical research based on natural products and their interaction with protein domains. Electron microscopy pictures of polymer beads and tumor cells are shown in the background. A 2-nm-thick gold layer was vaporized on to the resin beads. Tumor cells floating in front of the beads were employed in a cytotoxicity assay. The results of the assay are readily seen on the microtiter plates with the naked eye: living cells reduce a yellow tetrazolium salt to a red-violet dye. A detailed description of the study is reported by H. Waldmann et al. on p. 307 ff.