Synthesis and Conformational Analysis of Optically Active Ferrocene Containing Macrocyclic Peptides

Abstract

Two macrocyclic peptides 3 and 4 were formed during lactamization of 1,1'-ferrocenylbis(alanine) 1. Isolation, structure determination, and conformational analysis of 3 and 4 are reported as well as a controlled stepwise synthesis of 4 also including an improved route to 1. On the basis of their (1)H NMR spectra recorded at 300 K in DMSO-d(6), the dimer 3 and trimer 4 were found to be C(2) and C(3) symmetric, respectively. As appeared from computational analysis, the low-energy conformations of the macrocyclic peptides were nonsymmetric. Cyclic voltammetry revealed that the ferrocenyl moieties in 3 or 4 are electrochemically equal to ferrocene.

The synthesis and structural characterization of N-ortho-ferrocenyl benzoyl amino acid esters. The X-ray crystal structure of N-{ortho-(ferrocenyl)benzoyl}-l-phenylalanine ethyl ester

“…The incorporation of a ferrocene group onto proteins has shown the mediation of electron transfer between electrodes and the protein redox site [3,4]. The synthesis and structural characterization of novel N-ferrocenoyl and N-ferrocenyl amino acid and peptide derivatives has been reported [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. A review on bioorganometallic chemistry of ferrocene has recently been published [27].…”

Synthesis and characterization of novel N-para-ferrocenyl benzoyl dipeptide esters

“…For example, the incorporation of a ferrocene group onto proteins has shown the mediation of electron transfer between electrodes and the protein redox site [8]. Also the synthesis and structural characterization of N-ferrocenoyl and N-ferrocenyl amino acid and peptide derivatives has been reported [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. In addition ferrocene has been incorporated in drugs such as antibiotics, aspirin, anti-malarials and anti-cancer drugs such as tamoxifen [27][28][29][30].…”

The synthesis and structural characterization of novel N-meta-ferrocenyl benzoyl dipeptide esters

“…The stability of the ferrocenyl group and its derivatives, in addition to its spectroscopic, electrochemical properties and ease of use make it suitable for biological applications and conjugation with biologically important compounds. The synthesis and structural characterization of novel N-ferrocenoyl and N-ferrocenyl amino acid and peptide derivatives has been reported [8][9][10][11][12][13][14][15][16][17][18][19][20][21]. In addition ferrocene has been incorporated in drugs such as antibiotics, aspirin, anti-malarial drugs and anti-cancer drugs such as tamoxifen [22][23][24][25].…”