Amino acids cobalt derivatives

The introduction of redox activity through a Co11 center in place of redox-inactive Zn11 can be revealing. Carboxypeptidase B (another Zn enzyme) and its Co-substituted derivative were oxidized by the active-site-selective m-chloroperbenzoic acid.1209 In the Co-substituted oxidized (Co111) enzyme there was a decrease in both the peptidase and the esterase activities, whereas in the zinc enzyme only the peptidase activity decreased. Oxidation of the native enzyme resulted in modification of a methionine residue instead. These studies indicate that the two metal ions impose different structural and functional properties on the active site, leading to differing reactivities of specific amino acid residues. Replacement of zinc(II) in the methyltransferase enzyme MT2-A by cobalt(II) yields an enzyme with enhanced activity, where spectroscopy also indicates coordination by two thiolates and two histidines, supported by EXAFS analysis of the zinc coordination sphere.1210... 

The amidocarbonylation of aldehydes provides highly efficient access to N-acyl a-amino acid derivatives by the reaction of the ubiquitous and cheap starting materials aldehyde, amide, and carbon monoxide under transition metal-catalysis [1,2]. Wakamatsu serendipitously discovered this reaction when observing the formation of amino acid derivatives as by-products in the cobalt-catalyzed oxo reaction of acrylonitrile [3-5]. The reaction was further elaborated to an efficient cobalt- or palladium-catalyzed one-step synthesis of racemic N-acyl a-amino acids [6-8] (Scheme 1). Besides the range of direct applications, such as pharmaceuticals and detergents, racemic N-acetyl a-amino acids are important intermediates in the synthesis of enantiomeri-cally pure a-amino acids via enzymatic hydrolysis [9]. 

Vitamin Bjj (8.50, cobalamin) is an extremely complex molecule consisting of a corrin ring system similar to heme. The central metal atom is cobalt, coordinated with a ribofuranosyl-dimethylbenzimidazole. Vitamin Bjj occurs in liver, but is also produced by many bacteria and is therefore obtained commercially by fermentation. The vitamin is a catalyst for the rearrangement of methylmalonyl-CoA to the succinyl derivative in the degradation of some amino acids and the oxidation of fatty acids with an odd number of carbon atoms. It is also necessary for the methylation of homocysteine to methionine. 

Derivatives of the steroids androstene and pregnene have been transformed directly into A-acyl amino acids by an orthogonal catalysis procedure, utilizing [RhCl(nbd)]2 and Co2(CO)8 (Scheme 11). The rhodium phosphine catalyst (generated in situ in the presence of syn-gas and phosphine) affects hydroformylation of the internal olefin to generate aldehyde. In the presence of Co2(CO)8, A-acyl amino acids are obtained as the major products. An unstable amido alcohol intermediate, formed by reaction of the amide with aldehyde, is proposed to undergo cobalt-catalyzed GO insertion to yield the desired A-acyl amino acid. 

Complexes of other amino acids or their derivatives with cobalt(II) that have been investigated include dipeptides (120) these complexes have long been known to absorb dioxygen. For example, the mononuclear cobalt(II) complex of N, N,N", N "-diglycylethylenediaminete-traacetic acid (121) absorbs one mole of dioxygen per two moles of complex. This system has been proposed as a simple, convenient model system for the study of dioxygen complexes of cobalt(II) peptides in solution because of its relatively slow conversion to the irreversibly formed cobalt(III) dioxygen complex. 

In the case of amino acid ester and amide complexes, the intramolecular hydrolysis reaction was not observed directly, but was deduced from the results of lsO tracer studies. However, recently the cis-hydroxo and cis-aqua complexes derived from the bis(ethylenediamine)cobalt(III) system, containing glycinamide, glycylglycine and isopropylglycylglycinate, have been isolated and their subsequent cyclization studied over the pH range 0-14.160,161... 

The rates of hydrolysis of amino acid esters or amides are often accelerated a million times or so by the addition of simple metal salts. Salts of nickel(n), copper(n), zinc(n) and cobalt(m) have proved to be particularly effective for this. The last ion is non-labile and reactions are sufficiently slow to allow both detailed mechanistic studies and the isolation of intermediates, whereas in the case of the other ions ligand exchange processes are sufficiently rapid that numerous solution species are often present. Over the past thirty years the interactions of metal ions with amino acid derivatives have been investigated intensively, and the interested reader is referred to the suggestions for further reading at the end of the book for more comprehensive treatments of this interesting and important area. 

What effect does co-ordination of the amino acid derivative 3.1 have upon the rate of hydrolysis The rates of the hydrolysis reactions depicted in Fig. 3-8 are only slightly more rapid than those of the free amino acid esters, and, in general, the rates of reactions involving monodentate TV-bonded ligands very closely resemble those for acid-catalysed hydration. This monodentate bonding mode is only exhibited with non-labile ions such as cobalt(m) or chromium(m) and is relatively rare even then. 

In conclusion, the hydrolytic and other reactions of co-ordinated amino acid derivatives with nucleophiles may proceed by two major routes. The first involves a moderate acceleration by general acid catalysis of a monodentate TV-bonded ligand, whilst the second may involve very dramatic rate increases (by a factor of a million or so) associated with didentate chelating TV O-bonded ligands. There is little evidence for the widespread involvement of co-ordinated nucleophiles attacking the carbonyl in amino acid derivatives, although some special, and well characterised, examples with cobalt(m) complexes are considered in the next chapter. 

This is an important mechanism, and we have seen the consequences of attack by an intramolecular nucleophile (ligand) in earlier chapters. A particularly interesting example is seen in the intramolecular Michael addition of a co-ordinated amide at a cobalt(m) centre to yield an amino acid derivative (Fig. 5-44). 

A stimulating discussion of the chemistry cobalt(m) complexes of amino acid derivatives... 

Originally devised as a method for the conversion of amino acids or amino acid esters to aldehydes. The Akabori reaction has been modihed for use in the determination of C-terminal amino acids by performing the reaction in the presence of hydrazine and for the production of derivatives useful for mass spectrometric identihcation. See Ambach, E. and Beck, W., Metal-complexes with biologically important ligands. 35. Nickel, cobalt, palladium, and platinum complexes with Schiff-bases of... 

The Nicholas reaction was used to synthesize the p-lactam precursor of thienamycin in the laboratory of P.A. Jacobi and thereby accomplish its formal total synthesis. The necessary p-amino acid was prepared by the condensation of a boron enolate (derived from an acylated oxazolidinone) with the cobalt complex of an enantiopure propargylic ether. The resulting adduct was oxidized with ceric ammonium nitrate (CAN) to remove the cobalt protecting group from the triple bond, and the product was obtained with a 17 1 anti.syn selectivity and in good yield. 

Enantioselection can be controlled much more effectively with the appropriate chiral copper, rhodium, and cobalt catalyst.The first major breakthrough in this area was achieved by copper complexes with chiral salicylaldimine ligands that were obtained from salicylaldehyde and amino alcohols derived from a-amino acids (Aratani catalysts ). With bulky diazo esters, both the diastereoselectivity (transicis ratio) and the enantioselectivity can be increased. These facts have been used, inter alia, for the diastereo- and enantioselective synthesis of chrysan-themic and permethrinic acids which are components of pyrethroid insecticides (Table 10). 0-Trimethylsilyl enols can also be cyclopropanated enantioselectively with alkyl diazoacetates in the presence of Aratani catalysts. In detailed studies,the influence of various parameters, such as metal ligands in the catalyst, catalyst concentration, solvent, and alkene structure, on the enantioselectivity has been recorded. Enantiomeric excesses of up to 88% were obtained with catalyst 7 (R = Bz = 2-MeOCgH4). 

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