Cobalt complexes amino acid esters

Metal-ion catalysis has been extensively reviewed (Martell, 1968 Bender, 1971). It appears that metal ions will not affect ester hydrolysis reactions unless there is a second co-ordination site in the molecule in addition to the carbonyl group. Hence, hydrolysis of the usual types of esters is not catadysed by metal ions, but hydrolysis of amino-acid esters is subject to catalysis, presumably by polarization of the carbonyl group (KroU, 1952). Cobalt (II), copper (II), and manganese (II) ions promote hydrolysis of glycine ethyl ester at pH 7-3-7-9 and 25°, conditions under which it is otherwise quite stable (Kroll, 1952). The rate constants have maximum values when the ratio of metal ion to ester concentration is unity. Consequently, the most active species is a 1 1 complex. The rate constant increases with the ability of the metal ion to complex with 2unines. The scheme of equation (30) was postulated. The rate of hydrolysis of glycine ethyl... 

It has been known for many years that the rate of hydrolysis of a-amino acid esters is enhanced by a variety of metal ions such as copper(II), nickel(II), magnesium(H), manganese(II), cobalt(II) and zinc(II).338 Early studies showed that glycine ester hydrolysis can be promoted by a tridentate copper(II) complex coupled by coordination of the amino group and hydrolysis by external hydroxide ion (Scheme 88).339 Also, bis(salicylaldehyde)copper(II) promotes terminal hydrolysis of the tripeptide glycylglycylglycine (equation 73).340 In this case the iV-terminal dipeptide fragment... 

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... 

In the case of inert cobalt(m) complexes it is possible to isolate the chelated products of the reaction. Let us return to the hydrolysis of the complex cations [Co(en)2(H2NCH2C02R)Cl]2+ (3.1), which contain a monodentate iV-bonded amino acid ester, that we encountered in Fig. 3-8. The chelate effect would be expected to favour the conversion of this to the chelated didentate AO-bonded ligand. However, the cobalt(iu) centre is kinetically inert and the chloride ligand is non-labile. When silver(i)... 

We saw in Chapter 3 that the hydrolysis of chelated amino acid esters and amides was dramatically accelerated by the nucleophilic attack of external hydroxide ion or water and that cobalt(m) complexes provided an ideal framework for the mechanistic study of these reactions. Some of the earlier studies were concerned with the reactions of the cations [Co(en)2Cl(H2NCH2C02R)]2+, which contained a monodentate amino acid ester. In many respects these proved to be an unfortunate choice in that a number of mechanisms for their hydrolysis may be envisaged. The first involved attack by external hydroxide upon the monodentate A-bonded ester (Fig. 5-62). This process is little accelerated by co-ordination in a monodentate manner. 

Two mechanisms of cobalt(III)-mediated peptide-bond cleavage have been investigated. The first one involves hydrolysis of a directly activated amino acid ester, or peptide (equation 4). The other mechanism involves the intramolecular attack of an amino acid ester or peptide by a cis coordinated hydroxide or water molecule (equation 5). In both cases, the cobalt(III) complex must have two open coordination sites cis to each other. For the directly activated mechanism, these sites are needed to bind the amino acid ester or peptide. The intramolecular reaction requires one site for coordination of the ester or peptide, and one site for the coordination of the hydroxy or water molecnle. One of the initial cobalt(III) complexes to be investigated was... 

Owing to the snccess of cobalt(III)-mediated hydrolysis of amino acid esters, the next step was to examine how these complexes reacted with peptides. If similar hydrolytic results could be obtained with peptides, then one of the potential uses of cobalt(III) complexes would be in the N-terminal determination and seqnential analysis of polypeptides. This area has been investigated by several gronps. Peptides... 

The rate of hydrolysis of peptides by cobalt(III) complexes is 10" times faster than hydrolysis with no metal present. " Unlike the hydrolysis of amino acid esters, where the rate of hydrolysis is dependent on how the ester is bonded to the cobalt(III) complex, peptides are hydrolyzed equally if they are bound to the cobalt(III) complex in a monodentate fashion (throngh the carbonyl oxygen) or in a bidentate fashion (throngh the amino nitrogen and carbonyl oxygen). 

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... 

Toorisaka et al.87 studied the structure of the complex formed between a cobalt ion and alkyl imidazole that catalyses hydrolysis of an amino acid ester. By using HyperChem they calculated the lowest energy structure of the complex in vacuum. Then the complex was placed at the toluene-water interface by replacing 11 toluene molecules with molecules of water (Fig. 6.9). The MD simulation was performed in the (N, V, T) ensemble after MM calculation in the biphase system,... 

The cobalt(III)-promoted hydrolysis of amino acid esters and peptides and the application of cobalt(III) complexes to the synthesis of small peptides has been reviewed. The ability of a metal ion to cooperate with various inter- and intramolecular acids and bases and promote amide hydrolysis has been investigated. The cobalt complexes (5-10) were prepared as potential substrates for amide hydrolysis. Phenolic and carboxylic functional groups were placed within the vicinity of cobalt(III) chelated amides, to provide models for zinc-containing peptidases such as carboxypeplidase A. The incorporation of a phenol group as in (5) and (6) enhanced the rate of base hydrolysis of the amide function by a factor of 10 -fold above that due to the metal alone. Intramolecular catalysis by the carboxyl group in the complexes (5) and (8) was not observed. The results are interpreted in terms of a bifunctional mechanism for tetrahedral intermediate breakdown by phenol. 

Amino acid esters, amides, and peptides can be hydrolyzed in basic solution, and metal ions (Cu(II), Co(II), Ni(II), Mn(II), Ca(II), and Mg(II), and others) speed these reactions. The uncertain mechanism is either through bidentate coordination of the a-amino group and the carbonyl, or only through the amine. The rates of these reactions often exhibit complicated temperature dependence and deduction of the mechanism is difficult. Co(III) complexes promote similar reactions. When four of the six octahedral positions are occupied by amine ligands, and two cis positions are available for ligand substitution, these hydrolysis reactions can be examined in detail. These compounds generally catalyze the hydrolysis of N-terminal amino acids from peptides the amino acid that is removed remains bound to the metal. The reactions apparently proceed by coordination of the free amine to cobalt, followed either by coordination of the carbonyl to cobalt and snbseqnent reaction with OFI or H2O (path 1 in Figure 12.16) or reaction of the carbonyl... 

The hydrolysis of chelated amino acid esters, H2NCHRCO2R, is known to be accelerated by metal ions, most notably cobalt(III). Dramatic enhancements are also observed with copper(II). Mechanistic studies of the hydrolysis of amino acid esters with copper(II) complexes of glycyl-DL-valine and dien (H2HCH2CH2NHCH2CH2NH2) have been reported/ The hydrolysis of benzyl-penicillin (30) by copper(II) salts to give (31) has been further investigated, and it is proposed that the key step involves intramolecular attack by metal-coordinated hydroxide in an intermediate of type (32). 

Coordinated a-amino amides can be formed by the nucleophilic addition of amines to coordinated a-amino esters (see Chapter 7.4). This reaction forms the basis of attempts to use suitable metal coordination to promote peptide synthesis. Again, studies have been carried out using coordination of several metals and an interesting early example is amide formation on an amino acid imine complex of magnesium (equation 75).355 However, cobalt(III) complexes, because of their high kinetic stability, have received most serious investigation. These studies have been closely associated with those previously described for the hydrolysis of esters, amides and peptides. Whereas hydrolysis is observed when reactions are carried out in water, reactions in dimethyl-formamide or dimethyl sulfoxide result in peptide bond formation. These comparative results are illustrated in Scheme 91.356-358 The key intermediate (126) has also been reacted with dipeptide... 

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). 

---