Circular Aqueous Fmoc/t-Bu Solid-Phase Peptide Synthesis
Expert views
Circular economy and aqueous synthesis are attractive concepts for sustainable chemistry. Here it is reported that the two can be combined in the universal method for peptide chemistry, fluorenylmethoxycarbonyl(Fmoc)/t-Bu solid-phase peptide synthesis (SPPS). […]
According to one model there is no loss of peptide quality when SPPS waste is recycled by filtration over a mixed ion-exchange resin and then reused in synthesis. The following report demonstrates that Fmoc/t-Bu SPPS can be performed under aqueous conditions with standard Fmoc amino acids (AAs) using TentaGel S as the resin and a 4:1 mixture of water, as well as the low-cost green solvent PolarClean. This resin/solvent combination plays a critical dual role in improving resin swelling and the solubility of starting materials. This method in aqueous peptide chemistry also uses fewer starting materials. In addition, it eliminates the need to use unconventional or processed AAs in aqueous SPPS. It also significantly reduces the use of hazardous dipolar aprotic solvents. This method enables the efficient use of low-cost feedstock and the minimization of waste associated with universal Fmoc/t-Bu SPPS.
Pawlas, J.; Rasmussen, J. H., ChemSusChem 2021, 14, 3231–3236, DOI:10.1002/cssc.202101028.