(186ag) Process Intensification for Small Molecule Synthesis Via Recombinant Peptide Templated Palladium and the Elimination of Intermediate Purification

To illustrate the concept of process intensification for small organic molecule synthesis, a project was undertaken to test the catalytic ability of recombinant peptide-templated palladium nanoparticles (Pd NPs) in an impure environment. First, the soluble fraction of bacterial lysates containing repeat units of a metal binding domain (Pd4) fused to the carrier protein Green Fluorescent Protein was used to direct palladium nanoparticle synthesis without purification. Highly ordered NPs on the order of 2nm were prepared and then used for cross-coupling reactions commonly used in the pharmaceutical industry (e.g. the synthesis of the anti-cancer drug Tykerb). Data showed that Pd NPs without any purification could catalyze the synthesis of fifteen representative compounds via Suzuki or Stille cross-coupling reactions, with the purification of the drug analogs the only purification step of importance. Thus, by using a combination of green chemistry to both produce the catalyst particles and product we illustrate a “one pot process” that requires the minimum number of overall purification steps from start to final product.