Cobalt -amino acid chelates, synthesis

The rapid aminolysis of cobalt(llI)-chelated glycine esters in aprotic solvents (Scheme 10 N4 = (en)2 or trien, R = Me, Et, R = H, CHR"C02Et) could be of value in peptide synthesis. The cobalt atom acts as both an N-protecting and an activating group. The synthesis of the chelated amino acid esters has presented some difficulties.207 A recent paper208 describes the use of methyl trifluoromethanesulfonate for the alkylation of chelated amino acids using dry trimethyl phosphate... 

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. 

A number of methods for the preparation of labelled amino acids have appeared in 1976 unfortunately most are applicable to one acid only. However, an interesting development in this area is the reactions of cobalt(ii) chelates of chiral amino acids which undergo proton exchange at the 2-position at pH 9.9. Separation of the resulting diastereoisomers and regeneration of the amino-acid using borohydride leads to optically pure, labelled acids. This method is successful for a number of amino acids and reports of its use in the synthesis of [2- H-]aspartic acid and 5-(A -benzyl)-[2- H]glycinate have been published in addition to a discussion of the reaction mechanism. ... 

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