Iron amides bonding

Enterobactin is a cyclic triester of 2,3-dihydroxy-N-benzoyl-L-serine (Fig. 6). It is accumulated by E. coli and other bacteria when grown under low iron conditions and mediates the anabolic utilization of iron by these microbes, as do the hydroxamate siderochromes mentioned above (13, 21). In enterobactin, however, the metal-binding ligands are provided by catechol groups and the sustaining backbone is held together by ester, rather than by amide, bonds. 

A crystal structure of astin B (299) has been reported (Fig. 37) 182). The solid-state conformation exhibits one cis peptide bond between Abu and Pro. This structural feature is the main difference among the solid-state structures of the astins, cyclochlorotine I9I), and islanditoxin 192). The latter two compounds are toxic metabolites of yellow rice mold, Penicil-lium islandicum spp., whose occurrence on a variety of foodstuffs constitutes a human health hazard. In cyclochlorotine, only the astin Abu residue is replaced with serine, yet the molecule adopts a stable type I j8-turn conformation with a irons proline amide bond and a transannular hydrogen bond 191). 

Up to the present only two naturally-occurring N-hydroxypeptides have been isolated asparaginyl-L-a-N-hydroxyasparagine (46) (22) and aspartyl-L-a-N-hydroxyaspartyl-D-cycloserine (47) (23). The former was isolated from cultures of Mycobacterium avium, the latter (47) from Corynebacterium kutscheri. Both probably act as iron ionophores (siderophores) in these strains. It has also been reported (102) that in human brain tumor cell proteins one N-hydroxy amide bond occurs for every 300-500 amino acid residues. To date this has not been confirmed by other authors. 

Prilocaine was synthesised in 1960 and was found to be very similar to lidocaine. It has a wider safety margin which is probably because it has a lower partition coefficient (Table 15.1) than lidocaine and also the amide bond is more readily enzymatically hydrolysed than that in lidocaine. It does have an additional problem in that the 2-methyl aniline hydrolysis product of metabolism (Fig. 15.10) can cause methaemoglobinaemia, a condition where the oxygen-carrying capacity of blood cells is reduced due to oxidation of iron (II) in haemoglobin to iron (III). Prilocaine has a chiral centre but it is administered as racemate. However, it is only one of the enantiomers which are rapidly hydrolysed in the liver causing toxicity this provides an example of how chirality can influence therapeutic activity. 

The chemistry of indium metal is the subject of current investigation, especially since the reactions induced by it can be performed in aqueous solution.15 The selective reductions of ethyl 4-nitrobenzoate (entry 1), 2-nitrobenzyl alcohol (entry 2), l-bromo-4-nitrobenzene (entry 3), 4-nitrocinnamyl alcohol (entry 4), 4-nitrobenzonitrile (entry 5), 4-nitrobenzamide (entry 6), 4-nitroanisole (entry 7), and 2-nitrofluorenone (entry 8) with indium metal in the presence of ammonium chloride using aqueous ethanol were performed and the corresponding amines were produced in good yield. These results indicate a useful selectivity in the reduction procedure. For example, ester, nitrile, bromo, amide, benzylic ketone, benzylic alcohol, aromatic ether, and unsaturated bonds remained unaffected during this transformation. Many of the previous methods produce a mixture of compounds. Other metals like zinc, tin, and iron usually require acid-catalysts for the activation process, with resultant problems of waste disposal. 

The addition of acetic acid (0.5 equiv. to the substrate) to the catalyst system led to increased activity (doubling of yield) by maintaining the selectivity with 1.2 equiv. H2O2 as terminal oxidant. Advantageously, the system is characterized by a certain tolerance towards functional groups such as amides, esters, ethers, and carbonates. An improvement in conversions and selectivities by a slow addition protocol was shown recently [102]. For the first time, a nonheme iron catalyst system is able to oxidize tertiary C-H bonds in a synthetic applicable and selective manner and therefore should allow for synthetic applications [103]. 

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