Solid Phase Peptide Synthesis (SPPS) is a key technology for the production of pharmaceutical grade peptides, although it represents the worst modality in the pharma segment when considering its Process Mass Intensity (PMI). Consequently, academic and industrial research teams have focused their attention on greening SPPS protocols by introducing more sustainable alternatives to the most common reagents and solvents. In this context, 3-(diethylamino)propylamine (DEAPA) was identified to be a viable alternative to piperidine for Fmoc removal. In addition, the use of DEAPA in N-octyl-pyrrolidone (manual synthesis) or N-octyl pyrrolidone/dimethyl carbonate 8/2 v/v (automated synthesis) was proved to be able to minimize the formation of side products like diastereoisomers and aspartimide-containing derivatives.

Replacing piperidine in Solid Phase Peptide Synthesis: effective Fmoc removal by alternative bases

Giulia Martelli;Chiara Palladino;Alexia Mattellone;Dario Corbisiero;Tommaso Fantoni;Alessandra Tolomelli;Walter Cabri;Lucia Ferrazzano
2021

Abstract

Solid Phase Peptide Synthesis (SPPS) is a key technology for the production of pharmaceutical grade peptides, although it represents the worst modality in the pharma segment when considering its Process Mass Intensity (PMI). Consequently, academic and industrial research teams have focused their attention on greening SPPS protocols by introducing more sustainable alternatives to the most common reagents and solvents. In this context, 3-(diethylamino)propylamine (DEAPA) was identified to be a viable alternative to piperidine for Fmoc removal. In addition, the use of DEAPA in N-octyl-pyrrolidone (manual synthesis) or N-octyl pyrrolidone/dimethyl carbonate 8/2 v/v (automated synthesis) was proved to be able to minimize the formation of side products like diastereoisomers and aspartimide-containing derivatives.
GREEN CHEMISTRY
Giulia Martelli; Paolo Cantelmi; Chiara Palladino; Alexia Mattellone; Dario Corbisiero; Tommaso Fantoni; Alessandra Tolomelli; Marco Macis; Antonio Ricci; Walter Cabri; Lucia Ferrazzano
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/835787
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