Synthetic study of peptide aldehyde via acetal/thioacetal transformation: application for Lys/Ser-containing peptides

Abstract The preparation of peptide aldehydes via efficient transformation of acetal/thioacetal structures followed by treatment of N -bromo succinimide is described. Peptide acetals derived from the corresponding Fmoc-amino acids and hexane-1,2,6-triol were prepared by the conventional Fmoc-SPPS. Subsequently, the peptide acetals were efficiently converted to thioacetal structures followed by treatment of N -bromo succinimide to give peptide aldehydes. Since alkyl and phenyl-containing peptides were applied to give reasonable results in a previous report, we attempted the synthesis of three variant peptide aldehydes in the present study. A C-terminal Phe-containing peptide aldehyde, Ac-Leu-Ala-Phe-H ( 3 ), to compare the reactivity of C-terminal amino acids was designed and synthesized. In this case, the reactivity was guided by steric hindrance between acetal structures and side chains of selected amino acids. In contrast, the Lys-containing peptide aldehyde, Ac-Lys-Ala-Leu-H ( 4 ), and the Ser-containing peptide, Ac-Ser-Phe-Leu-H ( 5 ), were applicable. These results suggest that this methodology has good potential.