Rapid Removal of Protecting Groups from Peptides by Catalytic Transfer Hydrogenation with 1,4-Cyclohexadiene

Abstract

1,4-Cyclohexadiene is a very effective hydrogen donor for catalytic transfer hydrogenation. N-Benzyloxycarbonyl, benzyl ester, and benzyl ether (tyrosine) protecting groups can be rapidly removed at 25 °C with 1,4-cyclohexadiene and 10% palladium-carbon catalyst. Removal of the Nim-benzyl group from histidine, the Ng-nitro group from arginine, and the benzyl ether groups from serine and threonine can be carried out at 25 °C using palladium black as catalyst. Cleavage of N-benzyloxycarbonyl groups from sulfur-containing amino acids was also achieved by catalytic transfer hydrogenation with 1,4-cyclohexadiene. tert-Butyl-derived protecting groups were completely stable under these conditions. The scope of the 1,4-cyclohexadiene-catalyzed transfer hydrogenation for the removal of benzyl-derived protecting groups used in peptide synthesis was examined. © 1978, American Chemical Society. All rights reserved.