N-alkylation of pyridylalanine and pyridinecarboxylic acids and their use in synthesis of GnRH antagonists

Article abstract of DOI:10.1016/S0040-4039(00)79194-5

A mild N-alkylation method has been developed for the synthesis of N-alkylated pyridiniumcarboxylic acids, using Ag₂O-H₂O catalysis to enhance the low-reactivity of pyridinecarboxylic acids. Two approaches were undertaken for the synthesis of a series of GnRH antagonists containing pyridinium moieties at the side chain: (1) incorporation of Npy-alkylated D-pyridylalanine during solid phase peptide chain assembly, and (2) coupling of the N-alkylated pyridinium-carboxylic acid to the resin-bound ε-amino group of a D-lysine on a solid support.