Pseudoproline (oxazolidine) dipeptides
Pseudoproline dipeptides are undoubtedly the most powerful tools described to date for enhancing synthetic efficiency in Fmoc SPPS. They are particularly effective in the synthesis of intractable peptides, long peptides/small proteins, and cyclic peptides, enabling in many cases the production of peptides that otherwise could not be made. The insertion of a pseudoproline into a sequence disrupts the formation of the secondary structures thought responsible for problems during peptide assembly, leading to better and more predictable acylation and deprotection kinetics, improved yields, purities and solubilities of crude products, and easier HPLC purification with higher product return. Since the pseudoproline unit is stable to AcOH/TFE/DCM, peptides prepared on 2-chlorotrityl and NovaSyn® TGT resins can be isolated with the pseudoproline moiety still in place; this can be particularly advantageous when preparing peptides for use in fragment condensation reactions, as peptides containing pseudoproline residues often exhibit markedly improved solubility properties. Furthermore, peptides containing a C-terminal pseudoproline residue can be coupled without risk of epimerization.
