Synthesis of 14C-labelled peptides by asymmetric reduction of dehydroamino acids

The labelled dehydroamino acid, 2-N-acetylamino-3-(2-naphthyl)-3-[14C]-acrylic acid was prepared at 52.8 mCi/mmol from Ba14CO3. Asymmetric reduction of this precursor with hydrogen in the presence of the chiral homogeneous catalyst (S,S) BPPMRh+ afforded N-acetyl-D-3-(2-naphthyl)-3-[14C]-alanine in greater than 98% optical yield. This unnatural amino acid was used in a solution phase synthesis of 2 14C-labelled LHRH analogs, [N-Ac-D-3-[14 C] Nal1 D-p-Cl-Phe2, D-Trp3,D-hArg(Et2)6, D-Ala10] LHRH and [D-3-[14C] Nal6] LHRH having specific activities in excess of 50 mCi/mmol.