Synthesis and structure analysis of ferrocene-containing pseudopeptides

Ferrocene with its aromaticity and facile redox properties is an attractive moiety to be incorporated into functional moieties. Medicinal applications of ferrocene are well known and ferrocene itself shows cytotoxic and antianemic properties. In this article, we will describe the synthesis and the structure analysis of two pseudopeptides containing a ferrocene moiety as N-terminal group. After purification, Fc-L-Phe-D-Oxd-OBn [L-Phe=L-phenylalanine; D-Oxd=(4R,5S)-4-Methyl-5-carboxy-oxazolidin-2-one] appears as bright brown solid that spontaneously forms brown needles. The X-ray diffraction of the crystals shows the presence of strong p interactions between the ferrocenyl moiety and the phenyl rings, while no NAH center dot center dot center dot O=C hydrogen bonds are formed. This result is confirmed by FT-IR and H-1 NMR analysis. In contrast, both FT-IR and H-1 NMR analysis suggest that Fc-(L-Phe-D-Oxd)(2)-OBn forms a turn conformation stabilized by intramolecular NAH center dot center dot center dot O=C hydrogen bonds in solution. Chiroptical spectroscopies (ECD and VCD) substantially confirmed the absence of a well-defined folded structure. The presence of the Fc moiety is responsible for specific ECD signals, one of which displayed pronounced temperature dependence and is directly related with the helicity assumed by the Fc core. Solid-state ECD spectra were recorded and rationalized on the basis of the X-ray geometry and quantum-mechanical calculations.