Triethyl phosphate (TEP) as a green solvent for solid-phase peptide synthesis (SPPS)

ABSTRACTTriethyl phosphate (TEP) is a new member of the Green Solid-Phase Peptide Synthesis (GSPPS) toolbox. TEP shows almost no toxicity and no carcinogenic or mutagenic properties. It degrades, giving the rather innocuous phosphoric acid and ethanol. TEP has a low viscosity, which makes it appealing for solid-phase peptide synthesis (SPPS), where the reagents delivered by the solvent should penetrate the polymeric matrix. TEP dissolves most Fmoc-amino acids and key coupling reagents and additives. The use of TEP has allowed the SPPS of several model peptides using the most conventional polystyrene resin at room temperature, while other green solvents required more sophisticated resins and/or elevated temperatures. In conclusion, TEP is an excellent contender to become the green solvent of choice.