Ferrocenyl side chain

Third, metallocene units, such as ferrocene or ruthenocene, have been linked to phosphazene cyclic trimers or tetramers and these were polymerized and substituted to give polymers of the type mentioned previously (41). Polyphosphazenes with ferrocenyl groups can be doped with iodine to form weak semiconductors. Polymer chains that bear both ruthenocenyl and ferrocenyl side groups are prospective electrode mediator systems. 

Rh complexes with ChiraPhos, PyrPhos, or ferrocenyl phosphines lacking amino alkyl side chains (such as BPPFA) are much less active toward tetrasubstituted olefins. Table 6-1 shows that in asymmetric hydrogenations catalyzed by 5a-d, the coordinated Rh complex exerts high selectivity on various substrates. It is postulated that the terminal amino group in the ligand forms an ammonium carboxylate with the olefinic substrates and attracts the substrate to the coordination site of the catalyst to facilitate the hydrogenation. 

Synthetic peptides containing side-chain modification have also been used as molecular scaffolds for the preparation of multiple receptors and molecular devices. 5 These include the use of crown ethers, cyclodextrins, porphyrins, and peptides with metal-binding sites (including ferrocenyl and EDTA side chains) (Section 9.4). Cyclization procedures have been developed to prepare biologically active cycloisodityrosine peptides which contain 14-or 17-membered rings (Section 9.5). The use of tryptathionine, a cross-linking dipeptide consisting of side-chain-to-side-chain linked L-Trp-L-Cys that is present in phallotoxins, 6 a family of cyclic heptapeptides, is also described (Section 9.6). 

Note that these organic polymers with metallocenyl side groups are similar in general architecture to the polyphosphazenes with ferrocenyl side groups discussed in Chapter 3 in the sense that the ferrocene units are pendent to the main chain. 

Nguyen A, Top S, Pigeon P, Vessieres A, Hillard EA, Plamont M-A, Huche M, Rigamonti C, Jaouen G (2009) Synthesis and structure-activity relationships of ferrocenyl tamoxifen derivatives with modified side chains. Chem Eur J 15 684—696... 

Nguyen A, Top S, Vessieres A, Pigeon P, Huche M, Hillard EA, Jaouen G (2007) Organo-metallic analogues of tamoxifen effect of the amino side-chain replacement by a carbonyl ferrocenyl moiety in hydroxytamoxifen. J Organomet Chem 692 1219-1225... 

Exploiting the structure-based strategy, the quinuclidinyl and the piperidinyl side chains of quinine (QN) and mefloquine (MF) were, respectively, substituted with a ferrocene moiety while maintaining a basic amino group (Fig. 16). In vitro, lower activities than the parent compounds were reported [106], In acidic aqueous solution, these ferrocenyl analogs seemed to be unstable, leading to the formation of the presumably inactive carbeniums. 

Particular attention was devoted to studying the impact of the introduction of the ferrocenyl moiety into the lateral side chain of CQ, implicated in DV targeting. Moreover, the length of the side chain and the distance between the two exocyclic nitrogen atoms may both affect resistance against 4-aminoquinolines by P. falciparum [116, 117]. 4-aminoquinolines with shorter (two or three carbon atoms)... 

These structural modifications allow us to conclude that the in vitro antimalarial activity was not disturbed by slight modifications in the lateral basic side chain. To the contrary, when a second ferrocenyl group was introduced on the terminal nitrogen atom, the efficacy of compounds was markedly attenuated [118]. 

In a slightly different approach, the introduction of a metal complex is also possible as a metallo amino acid. For example, ferrocenyl-alanine (Fer) was prepared as early as 1957 [67]. Also, stereoselective preparations [68-71] and its biological activity were reported [72], and the compound has been inserted into peptide sequences just as a normal amino acid would (see Fig. 7 for an example) [35, 71]. In this case, the metallocene constitutes the side chain. Alternatively, the amino and carboxylic acid function can be on two different Cp rings, yielding, in the simplest possible case, l -aminoferrocene-l-carboxylic acid (Fca, see Fig. 7 for an example). This compound has also been reported in the literature, although it was difficult to obtain in pure form [73,74], It has since been incorporated into oligomers... 

Asymmetric AUylation. Asymmetric allylation of p-diketones using the palladium analog of (1) has been described. Higher enantioselectivity can be achieved in this case using ferrocenylamines with a modified alkyl side chain. For synthetically useful ferrocenylamine complexes of other metals, see (R)-N-[2-(N,N-Dimethylamino)ethyl]-N-methyl-l-[(S)-l, 2-bis-(diphenylphosphino)ferrocenyl]ethylamine. 

A ferrocene modified siloxane redox polymeric electron transfer system in carbon paste electrodes for aldose biosensors using PQQ-dependent aldose dehydrogenase was reported by Smolander et al. [86]. Polymethyl(ll-ferrocenyl-4,7,10-trioxa-undecanyl)methyl(12-amino-4,7,10-trioxa-dodecyl)-siloxane (1 1 random co-polymer) (Fig. 3.6) was found to be an efficient electron transfer system yieldii better electrode operational stabiUty than those constructed with dimethylferrocene fi ee mediator. The hydrophilic nature of the pendant chain and side chain on dimethyl siloxane units favorably interact with enzjnne causing efficient electron transfer from coenzyme PQQ of aldose dehydrogenase to the electrode surface. 

The complexes with the shortest dimethyl amino side chains (n = 2, 3, or 4) retain the best affinity for the two forms of the estradiol receptor. On MCF7 hormone-dependent breast cancer cells, the anti-proliferative effect of these complexes at molarities of 1 xM is slightly stronger than that of OH-Tam for complexes where = 3 and 5 3b and 3d, and this effect is not completely suppressed by addition of estradiol. This seems to indicate that the observed anti-proliferative effect is the combination of an antihormonal effect linked to the tamoxifen skeleton and mediated by the estradiol receptor, and a cytotoxic effect induced by the presence of the ferrocenyl substituent. In fact, the cytotoxic properties of the ferricinium cation (Fc ), which is easily formed by oxidation in biological media, are well known.It should however be noted that ferrocene alone has no effect despite being able to enter cells without difficulty. 

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