Diversity‐Oriented Synthesis of Pochonins and Biological Evaluation against a Panel of Kinases

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Abstract
Pochonins A–F were recently characterized as six new members of the naturally occurring family of 14‐membered resorcylic acid lactones. As there are a high number of ATPase and kinase inhibitors among natural resorcylic lactones, a library based on the pochonin scaffold, with five points of diversity, was prepared which includes diversity beyond that of the natural analogues. The library was synthesized by using solid‐supported reagents amenable to automation. Testing the library for its inhibition against a panel of 24 kinases at 10 μM afforded a >14 % hit rate. These results demonstrate the potential of the resorcylides towards the inhibition of therapeutically relevant kinases.