Ferrocene amino acid

Scheme 12.8 Synthesis of ferrocene amino acid according to Heinze (i) f-BuLi, -70°C (ii) quenching with iodine (iii) reaction in pyridine with phthalimide and Cu20 as catalyst (iv) hydrazinolysis in ethanol (v) A-acetylation with Ac20 (vi) selective Friedel-Crafts acylation with 2,6-dichlorobenzoyl chloride at the unsubstituted Cp ring (vii) base hydrolysis (viii) removal of the acetyl protection group with hydrochloric acid.

In 1957, Schlogl reported the synthesis and characterization of several ferrocene amino acids, including ferrocenylala-nine (Fer, 14 Scheme 18). Other organometallic amino acids include alanine, phenylalanine (Phe), glycine derivatives, as well as further ferrocene-based amino acids, which are discussed below. The Schlogl paper also describes the reaction of ferrocene carboxylic acid and ferrocene carbaldehyde with amino acids. The chemistry was later picked up in numerous publications, and ferrocene carboxylic acid amides or ferrocene imines with basically all amino acids and many dipeptides were reported. Such conju tes may serve as ligands for other transition metal ions. " Kraatz has prepared ferrocene carboxylic acid conju tes with short peptides that serve as enzyme inhibitors. ... 

The dimeric complex 39 exhibits individual Fe(III)/ Fe(II) redox couples at +0.47 and +0.60 V v. SCE in CH2CI2. The averaged value (+0.54 V) is close to that of the corresponding monomeric complex 38 (+0.51 V). These results are explained by the electronic effect as reported in the literature. The trimer 40 exhibits two redox couples at +0.51 and +0.67 V in a similar condition. The positive peak suggests the presence of significant electronic interaction between two ferrocene units (center and C-terminus). This result indicates the possibility of constructing an expanded conjugation system of polymeric ferrocene amino acid and the development of the conductive devices by partial oxidation. 

Keywords Ferrocene Amino acid Peptide Hydrogen bond ... 

As for sensor technologies, chemical sensors can be used for detecting CWAs. Electrochemical sensors composed of multiwalled carbon nanotubes on indium tin oxide surfaces in connection with ferrocene-amino acid conjugates have been developed for detecting nerve gas... 

Khan, M.A.K., Kerman, K., Petryel, M., et al, 2008. Noncovalent modification of carbon nanotubes with ferrocene-amino acid conjugates for electrochemical sensing of chemical warfare agent mimics. Anal. Chem. 80, 2574-2582. 

The rhodium complexes of the ferrocene derivatives 39 have shown useful characteristics for the reduction of itaconates as well as dehydroamino acid derivatives [15, 167-170]. These compounds are hybrids between ferrocene-based ligands and the various other types. The P-chiral compounds, which in some ways are DIPAMP hybrids, showed tolerance for the reduction of N-methyl en-amides to produce N-methyl-a-amino acid derivatives [169-171]. 

Another methodology for the in situ preparation of nitrile oxide is the dehydro-halogenation of hydroxymoyl chlorides vrith triethylamine. Hydroxymoyl chlorides are accessible by the reaction of aldoximes vrith chlorinating agents such as NCS (N-chlorosuccinimide). Isoxazolines of C50 and C70 [293-295] with R = Ph, alkyl, 4-C5H4OCH3 4-C5H4CHO, amino acid [305], dialkoxyphosphoryl [296, 297] or ferrocene [298] have been synthesized in ca. 20 0% yields. The latter reaction is slower than the dehydration of nitroalkanes and requires one equivalent of hydroxymoyl chloride whereas excess nitroalkane is necessary for an optimum reaction [293]. 

The relatively low value is attributed to the absorption of the ferrocene fragment at 280 nm. The isoelectrofocusing of Fc-HPR confirmed its homogeneity with the expectedly shifted isoelectric point to a more basic pH (cf. 8.1 and 8.5 for HRP and Fc-HRP, respectively). Cyclic voltammetry experiments indicated the ferrocene moiety in Fc-HRP (Fig. 12). New anodic and cathodic peaks are around 360 and 300 mV, respectively (Fig. 12b). The redox potential of 327 mV for Fc-HRP is shifted anodically compared with that for Fc-Hemin in water (264 mV). This may indicate that the ferrocene unit is shielded by amino acid residues located in the vicinity of the active site. 

Figure 10.6 The intramolecular interstrand H-bonding pattern in amino acid conjugates of disubstituted Fc derivatives results in the formation of 10-membered rings for ferrocene dicarboxylic acid conjugates, 12-membered rings forFca-conjugates, and 14-membered rings for ferrocenediamine conjugates. Reproduced by permission from Ref. 50 of The Royal Society of Chemistry.

Norbomene was functionalized with cyclodextrins and surface grafted onto silica-based supports using ROMP (44). The CSP are suitable for the enantioselective separation various amino acids, including jS-blockers and other compounds, such as chiral ferrocene derivates. 

The ubiquitous electrochemical behavior of ferrocene and its relative chemical stability have made this organometallic complex a useful group for the preparation of redox-active devices. The incorporation of ferrocene-modified amino acids into larger polypeptide structures can therefore lead to electrochemically active de novo designed proteins. In addition, the attachment of ferrocene derivatives to peptides make them electroactive and eligible to electrochemical detection. Hence, it is not surprising that the first synthesis of a ferrocene-modified amino acid dates back to the 1950s. 

Dominguez et al. [71] L-Amino acids D-Amino acids Grapes r,-Amino acid oxidase or D-amino acid oxidase and peroxidase/entrapped in electrode composite matrix by physical inclusion Graphite-Teflon-ferrocene composite electrode/OV vs. Ag/AgCl Ferrocene... 

C-H functionalizations, 10, 115 ferrocene-based receptors for, 12, 486-487 hydrophobic, via zinc compounds, 9, 97 phosphine-containing, supports for, 12, 700-701 a-Amino acids... 

Debroy, P., Banerjee, M., Prasad, M., Moulik, S. R, Roy, S., Binding of amino acids into a novel multiresponsive ferrocene receptor having an ene backbone. Org. Lett. 2005, 7, 403-406. 

The substituted ferrocenes 757 are widely used as metal-ligand systems. These compounds have a great variety of chelating groups (R) (1-diketones (a) [458], semicarbazones and thiosemicarbazones (b) [458], azomethines and their analogues (c) [458-462], oximes (d), carbonic, thiocarbonic (e), and amino acids (f) [458] ... 

Fig. 2 General scheme for the coupling of ferrocene carboxylic acid to amino acids and peptides...

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