Ethyl substituted coumarin-4-yl derivatives as photoremovable protecting groups for amino acids with improved stability for SPPS

The synthesis, photochemical properties and chemical stability of 7-(N,N-diethylamino-coumarin-4-yl)-1-ethyl (DEACE) photoremovable protecting group for carboxylic acids are presented. We demonstrate that the ethyl substituent of DEACE improves the hydrolytic stability of the protected ester in basic conditions used in solid phase peptide synthesis (SPPS) and retains the good photochemical properties of the coumarin-4-yl methyl derivatives. DEACE allows the preparation of peptides with protected carboxylic side groups with high yield via SPPS.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A methylated derivative of a coumarin-4-yl photosensitive cage was synthesized. ► Methyl substitution retains the photochemical properties of the coumarin-4-yl cage. ► Aspartic acid was modified with the new cage at the side chain carboxylic acid group. ► Methyl substitution enhances the stability of the ester bond during SPPS.