Studies on Peptides XVIII. Catalytic Hydrogenation of Methionine-containing Peptides

Abstract

Under anhydrous conditions, the N^a-benzyloxycarbonyl group attached to methionine was quantitatively removed by catalytic hydrogenation over a palladium catalyst in the presence of boron trifluoride etherate in methanol. Application of this procedure for the synthesis of methionine-peptides was demonstrated by the successful preparation of the C-terminal pentapeptides of eledoisin and physalaemin. Phenylalanylisoleucylglycylleucylmethionine amide and phenylalanyltyrosylglycylleucylmethionine amide were prepared by hydrogenation of the corresponding N^a-benzyloxycarbonyl derivatives in quantitative yield. It was shown also that arginylmethionine methyl ester could be prepared by catalytic hydrogenation of N^a-benzyloxycarbonyl-N^G-nitroarginine methyl ester. Partial methylation of the free carboxyl group is one of the side reaction in this procedure. Scope and limitation of catalytic hydrogenation of the benzyloxycarbonyl group in the presence of boron halides in anhydrous organic solvents were examined.