Morpholine (50%–60%) in dimethylformamide efficiently removes Fmoc in solid-phase peptide synthesis, minimizes the formation of diketopiperazine, and almost avoids the aspartimide formation. As morpholine scores 7.5 in terms of greenness, it is a great substitute for other bases such as piperidine.
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.
