In peptide synthesis, the issues related to poor sustainability, long reaction times and high process mass intensity (PMI) are necessary to promote actions aimed at redefining procedural aspects pro jected towards more sustainable synthetic processes. Herein, we report a fast, widely applicable and green solution-phase peptide synthesis (GSolPPS) via a continuous protocol using propylpho sphonic anhydride T3P® as the coupling reagent and N-benzyloxycarbonyl-protecting group (Z), which is easily removed by hydrogenation. Because N,N-dimethylformamide (DMF) replacement was a priority, the iterative process was per formed in EtOAc, pushing further on overall sustainability. The efficiency of the synthetic protocol in terms of conversion, racemi zation and reaction times allowed extending the scope of the work to the synthesis of the standard peptide Leu-enkephalin as a proof of concept. Among the various explored procedures, the one-pot protocol (Acont plus), avoiding work-ups, intermediate purification and any dispersion effect, allowed the achievement of PMI = 30 for each deprotection/coupling sequence necessary to introduce a single amino acid in the iterative process, without considering the possibility of solvent and base recovery. This value is the lowest reported for an oligopeptide synthesis protocol to date

Speeding up sustainable solution-phase peptide synthesis using T3P® as a green coupling reagent: methods and challenges / Mattellone A.; Corbisiero D.; Ferrazzano L.; Cantelmi P.; Martelli G.; Palladino C.; Tolomelli A.; Cabri W.. - In: GREEN CHEMISTRY. - ISSN 1463-9270. - ELETTRONICO. - 25:(2023), pp. 2563-2571. [10.1039/d3gc00431g]

Speeding up sustainable solution-phase peptide synthesis using T3P® as a green coupling reagent: methods and challenges

Mattellone A.;Corbisiero D.;Ferrazzano L.
Membro del Collaboration Group
;
Cantelmi P.;Martelli G.;Palladino C.;Tolomelli A.
;
Cabri W.
2023

Abstract

In peptide synthesis, the issues related to poor sustainability, long reaction times and high process mass intensity (PMI) are necessary to promote actions aimed at redefining procedural aspects pro jected towards more sustainable synthetic processes. Herein, we report a fast, widely applicable and green solution-phase peptide synthesis (GSolPPS) via a continuous protocol using propylpho sphonic anhydride T3P® as the coupling reagent and N-benzyloxycarbonyl-protecting group (Z), which is easily removed by hydrogenation. Because N,N-dimethylformamide (DMF) replacement was a priority, the iterative process was per formed in EtOAc, pushing further on overall sustainability. The efficiency of the synthetic protocol in terms of conversion, racemi zation and reaction times allowed extending the scope of the work to the synthesis of the standard peptide Leu-enkephalin as a proof of concept. Among the various explored procedures, the one-pot protocol (Acont plus), avoiding work-ups, intermediate purification and any dispersion effect, allowed the achievement of PMI = 30 for each deprotection/coupling sequence necessary to introduce a single amino acid in the iterative process, without considering the possibility of solvent and base recovery. This value is the lowest reported for an oligopeptide synthesis protocol to date
2023
Speeding up sustainable solution-phase peptide synthesis using T3P® as a green coupling reagent: methods and challenges / Mattellone A.; Corbisiero D.; Ferrazzano L.; Cantelmi P.; Martelli G.; Palladino C.; Tolomelli A.; Cabri W.. - In: GREEN CHEMISTRY. - ISSN 1463-9270. - ELETTRONICO. - 25:(2023), pp. 2563-2571. [10.1039/d3gc00431g]
Mattellone A.; Corbisiero D.; Ferrazzano L.; Cantelmi P.; Martelli G.; Palladino C.; Tolomelli A.; Cabri W.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/921913
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