Synthesis of 5--10,11-dihydrodibenzocyclohepten-2-yl>oxy>valeric Acid (CHA) and 5-dibenzocyclohepten-2-yl>oxy>valeric Acid (CHE) Handles for the Solid-Phase Synthesis of C-Terminal ...

Article abstract of DOI:10.1021/jo00105a010

Two novel handles for peptide amide preparation under mild conditions were developed for use in highly efficient solid-phase peptide sythesis.These handles, 5-<<(R,S)-5-<(9-fluorenylmethoxycarbonyl)amino>-10,11-dihydrodibenzocyclohepten-2-yl>oxy>valeric acid (CHA) and 5-<<(R,S)-5-<(9-fluorenylmethoxycarbonyl)amino>dibenzocyclohepten-2-yl>oxy>valeric acid (CHE), were attached to the solid support and were used for syntheses of peptides having a C-terminal amide by the fluorenylmethoxycarbonyl strategy.The cleavability of CHA and CHE was determined and compared with the that commercially available amide handles.CHA and CHE handles can be rapidly cleaved from the polymer support without significant side reactions using lower acid concentrations than those required for conventional handles.As CHA can be easily synthesized in large amounts, it is suitable for peptide amide preparation for pharmaceuticals.As CHE can be cleaved at very low concentrations of acid, it is especially suitable for preparing side chain-protected peptide amides.Several brain-gut peptides having a C-terminal amide were synthesized in high yield and high purity with these novel handles.