Microwave-Assisted Green Solid-Phase Peptide Synthesis Using γ‑Valerolactone (GVL) as Solvent

The increasing demand for synthetic peptides in various research fields raises a challenge, namely, the development of greener methods for their preparation. Here we report on an ecofriendly solid-phase peptide synthesis (SPPS) methodology. Substitution of the hazardous solvent DMF by the biomass-derived organic solvent γ-valerolactone (GVL), together with the application of microwave-assisted automated SPPS, allowed the synthesis of peptides with a wide range of lengths and high purity using polystyrene- and polyethylene-glycol-based resins. The yields achieved were comparable to those obtained with standard methodologies. To date, this is the greenest approach reported in terms of the solvent used, waste generated, and energy efficiency.