Tryptophan reduction and histidine racemization during deprotection by catalytic transfer hydrogenation of an analog of the luteinizing hormone releasing factor

(d -Trp)⁶-LHRH:pGlu-His-Trp-Ser-Tyr-d -Trp-Leu-Arg-Pro-GlyNH₂ was prepared by solid-phase peptide synthesis using the nitro group to protect the guanidine side chain of the arginyl residue. Removal of the side-chain protecting groups was carried out by catalytic transfer hydrogenation (CTH) using palladium acetate/ammonium formate or palladium on charcoal/formic acid. We show in this paper that this deprotection method induces i) reduction of the tryptophan residue and ii) epimerization at the histidine level (with palladium acetate/ammonium formate). Despite the formation of significant amounts of reduced peptide. CTH enabled us to obtain (d -Trp)⁶-LHRH in relatively good yield.