Green Solid-Phase Peptide Synthesis (GSPPS) 3. Green Solvents for Fmoc Removal in Peptide Chemistry

Abstract:

DMF (N,N-dimethylformamide) is the most widely used solvent for Fmoc-SPPS, which is the conventional method of choice for peptide synthesis. It is usually employed for coupling, washing, and Fmoc-removal steps. We have recently reported greener solvents such as 2-MeTHF (2-methyltetrahydrofuran) and CPME (cyclopentyl methyl ether) as environmentally friendlier alternatives to DMF. However, the Fmoc-removal step with these green solvents was not optimal. Thus, deletion peptides and Nα-Fmoc terminal peptides were observed upon TFA (trifluoroacetic acid) cleavage of the peptide from the resin during SPPS of a challenging aggregated peptide. Herein, Fmoc removal using a solution of 20% piperidine in a range of green solvents is reported. After evaluation of the resin's swelling (PS and ChemMatrix resins), and Fmoc deprotection in solution and on solid-phase for these two resins, it was found that valerolactone can replace DMF for Fmoc removal steps during SPPS on both resins, PS or ChemMatrix. Furthermore, N-formylmorpholine showed an excellent performance with ChemMatrix resin.

Año de publicación:

2017

Keywords:

• Solid-phase peptide synthesis
• valerolactone
• Green solvents
• Protecting groups
• Peptide aggregation
• Fmoc

Fuente:

scopus