(315b) Award Submission: 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 2 nm 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.