op9b00398_si_001.pdf (2.8 MB)
Diffusion-Enhanced Amide Bond Formation on a Solid Support
journal contribution
posted on 2019-11-20, 21:04 authored by Johnny
N. Naoum, Israel Alshanski, Agata Gitlin-Domagalska, Moshe Bentolila, Chaim Gilon, Mattan HurevichMixing of polystyrene resins in solid-phase synthesis
is performed
by 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 use fast overhead stirring
for performing coupling reactions on a solid support. We show that
fast overhead stirring enhances the efficiency of amide bond formation
on the solid support compared to the state-of-the-art mixing method,
while preserving the integrity of the beads. We find that fast overhead
stirring minimizes the effect of decomposition of the activated species
by increasing the diffusion-dependent coupling reaction. This allows
decreasing the excess of reagents used for the multistep synthesis
of peptides, thus providing a greener and more sustainable alternative
for peptide synthesis on solid supports.