Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors
European Journal of Organic Chemistry, 2010, DOI: 10.1002/ejoc.201090055, Volume 2010, Issue 21, page n/a published on 12.07.2010
European Journal of Organic Chemistry, online article
A convergent synthesis of SylA was developed and consists of the synthesis of a fully functionalized macrocycle, which is subsequently coupled with a urea moiety. For cyclization, ring-closing metathesis of a conformationally preorganized precursor was employed. The established synthetic route was then applied to the synthesis of SylA derivatives by using various peptidic side chains for decoration of the SylA macrocycle. The resulting collection of SylA analogues was tested for proteasome inhibition, revealing PEGylated SylA derivatives as the most potent proteasome inhibitors.