Solid‐phase peptide synthesis on a novel hydrogenolysable linker–resin combination

Abstract

AbstractThe propensity of benzyloxycarbonylamide group towards clean and rapid hydrogenolysis was exploited in designing a linker for solid phase peptide synthesis on a copoly(styrene–divinylbenzene) resin support. Hydroxymethyl copoly(styrene–divinylbenzene) on treatment with 4‐nitrophenyl chloroformate gave a resin which possessed benzyl 4‐nitrophenyl carbonate pendants. These reacted with the α‐amino group of Boc–Lys–OMe, resulting in the attachment of the latter through its side chain to the resin by a benzyloxycarbonylamide linkage. This was used to extend the peptide chain from the α‐amino end of lysine by Bocmethodology. The peptide was released from the resin through palladium acetate–ammonium formate‐based transfer hydrogenolysis. The usefulness of this linker was demonstrated by synthesizing several small peptides terminating in lysine. © 1995 John Wiley & Sons, Inc.