Synthesis and Characterization of Hydroxyproline Ferrocene-Conjugated Derivatives

The synthesis of ferrocene-hydroxyproline amino acid conjugates was carried out usingstandard peptide coupling conditions in solution. The coupling of hydroxyproline (Hyp)derivatives 3 and 4 with 1-ferrocene monocarboxylic acid (Fc-COOH) (1) gave 75-90% yield ofcompounds 5 and 6, while the reaction with the glycine-hydroxyproline dipeptide 11 gave about40% of conjugate 12. The reaction of 1,1’-ferrocene dicarboxylic acid (Fc(COOH)2) (2) with 3, 4 and 11 produced the corresponding Ferrocene-conjugated derivatives 7, 8 and 13 in acceptable yields (30-45%). All compounds were characterized by NMR, IR, MS and circular-dichrosim spectroscopy (CD). CD-spectroscopy of compound 13 showed P-helical conformation of Fc in solution (1,2’-conformer), and for compound 7 showed no absorption which suggests the 1,3’- conformation pattern.