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Morpholine, a strong contender for Fmoc removal in solid‐phase peptide synthesis

Sinenhlanhla N. Mthembu, Amit Chakraborty, Ralph Schönleber, Fernando Alberício, Beatriz G. de la Torre

2023Journal of Peptide Science16 citationsDOIOpen Access PDF

Abstract

Morpholine, which scores 7.5 in terms of greenness and is not a regulated substance, could be considered a strong contender for Fmoc removal in solid-phase peptide synthesis (SPPS). Morpholine in dimethylformamide (DMF) (50%-60%) efficiently removes Fmoc in SPPS, minimizes the formation of diketopiperazine, and almost avoids the aspartimide formation. As a proof of concept, somatostatin has been synthesized using 50% morpholine in DMF with the same purity as when using 20% piperidine-DMF.

Topics & Concepts

MorpholinePiperidineChemistrySolid-phase synthesisPeptide synthesisAminolysisCombinatorial chemistryDimethylformamidePeptideOrganic chemistryStereochemistryBiochemistryCatalysisSolventChemical Synthesis and AnalysisChemical Synthesis and ReactionsPeptidase Inhibition and Analysis