Diffusion Enhanced Amide Bond Formation on Solid Support


Johnny Naoum, Israel Alshanski, Agata Gitlin Domagalska, Moshe Bentolila, Chaim Gilon, and Mattan Hurevich. 2019. “Diffusion Enhanced Amide Bond Formation on Solid Support.” Organic Process Research & Development.
Diffusion Enhanced Amide Bond Formation on Solid Support


Mixing of polystyrene resin in solid phase synthesis is performed using shaking or gentle agitation of the reaction vessel to avoid breaking the brittle beads. These mixing strategies result in poor diffusion to and into the beads. Using a large excess of reagents is the common way to compensate for these deficiencies. We used fast overhead stirring for performing coupling reactions on the solid support. We show that fast overhead stirring enhances the efficiency of amide bond formation on solid support compared to the state-of-the-art mixing method while preserving the integrity of the beads. We found that fast over overhead stirring minimizes the effect of decomposition of the activated species by increasing the diffusion dependent coupling reaction. This allows to decrease the excess of reagents used for the multi-step synthesis of peptides, thus, provides greener and more sustainable alternative for peptide synthesis on solid support.


Last updated on 11/19/2021