2D green SPPS: green solvents for on-resin removal of acid sensitive protecting groups and lactamization
Aiming at greener synthesis of complex peptides we report that conventional one-dimensional (1D) green solid-phase peptide synthesis (SPPS) is elevated to a two-dimensional (2D) concept […]
Aiming at greener synthesis of complex peptides we report that conventional one-dimensional (1D) green solid-phase peptide synthesis (SPPS) is elevated to a two-dimensional (2D) concept in which side chains in peptide resins are functionalized by suitable green tactics. Specifically, we disclose on-resin deblocking using trifluoroacetic acid (TFA)/triisopropylsilane (TIS) in EtOAc/MeCN used in a synthesis of a melanocortin receptor agonist comprising (i) 1D green SPPS (ii) 2D green SPPS by an on-resin TFA/TIS in EtOAc/MeCN deprotection of Lys(Mtt) and Asp(O-2-PhiPr) followed by a lactamization using PyBOP/DIEA in NBP/EtOAc (iii) TFA cleavage followed by green precipitation using 4-methyltetrahydropyran (MTHP)/n-heptane. A further application for our green deprotection protocol was found in peptide fragment cleavages off CTC resins.Green solvents for on-resin removal of acid sensitive protecting groups and lactamization, Green Chem., 2019, 21, 2594.
J. Pawlas, B. Antonic, M. Lundqvist, T. Svensson, J. Finnman, J. H. Rasmussen, 2D Green SPPS:
DOI: 10.1039/c9gc00898e