Triphosgene as highly efficient reagent for the solid-phase coupling of N-alkylated amino acids—total synthesis of cyclosporin O

A novel, highly efficient and racemization free coupling procedure for sterically hindered N-alkyl amino acids has been developed using triphosgene and a combination of diisopropylethyl amine (DIEA) and collidine at room temperature. Its efficiency was demonstrated by comparison with other coupling methods for N-alkylated amino acids and by solid-phase synthesis of the immunosuppressant Cyclosporin O which was obtained in excellent purity and yield.