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

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Abstract
(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.