Copper transamination

The deamination of primary amines such as phenylethylamine by Escherichia coli (Cooper et al. 1992) and Klebsiella oxytoca (Flacisalihoglu et al. 1997) is carried out by an oxidase. This contains copper and topaquinone (TPQ), which is produced from tyrosine by dioxygenation. TPQ is reduced to an aminoquinol that in the form of a Cu(l) radical reacts with O2 to form H2O2, Cu(ll), and the imine. The mechanism has been elucidated (Wihnot et al. 1999), and involves formation of a Schiff base followed by hydrolysis in reactions that are formally analogous to those involved in pyridoxal-mediated transamination. 

The ability of peptides CBPOl-GBP 18 to modulate pyridoxamine-mediated transamination was determined by the conversion of pyruvic acid to alanine in both the absence and presence of copper(II) ion, which would be coordinated by the transamination intermediates [32]. In the absence of copper(II) ion,peptide CBP13 showed up to a 5.6-fold increase in alanine production relative to a pyridoxamine model compound and peptide CBP14 produced alanine with a 27% ee of the 1-enantiomer. In the presence of copper(II) ion, peptide CBP13 again showed the greatest increase in product production, with a 31.7-fold increase in alanine production relative to the pyridoxamine model compound. Peptide CBPIO showed optical induction for D-alanine with a 37% ee. 

In benzylamine oxidase there is evidence that the amine undergoes transamination with the pyridoxal prosthetic group to give a pyridoxamine, which is then oxidized by dioxygen to give H202 and NH3. The role for the copper is one of activation of the substrate.1346... 

Figure 3-22. Transamination of bis(/V,/V-diethyldithiocarbamato)copper(n) with a secondary amine.

Although transesterification and transamidation reactions of simple carbonyl ligands are usually associated with the involvement of a co-ordinated nucleophile, there are some well-documented processes which unambiguously involve attack by an external nucleophile upon a co-ordinated electrophile. Dithiocarbamate complexes contain a chelated. S, 5"-bonded dithioamide ligand and undergo facile transamination reactions upon treatment of the copper complexes with amines (Fig. 3-22). 

In some cases, the function of the metal ion is more to deactivate alternative sites of reaction than to activate a particular atom towards attack by an electrophile. A good example of this is seen in the transamination reaction of ornithine (5.12) with urea. Co-ordination of the ornithine to copper(n) results in the formation of a five-membered chelate ring, leaving the amino group of the 3-aminopropyl substituent as the most nucleophilic site in the complex. Reaction of this complex with urea results in a transamination process and the formation of the copper(n) complex of the substituted urea, which is the amino acid citrulline (5.13) (Fig. 5-20). The complex may be demetallated to yield the free amino acid in respectable yields. 

Transesterification or transamination are metal-directed reactions which are commonly encountered. We have discussed transamination processes in Section 5.5.2 and also in Chapter 3. The key step involves the attack of a co-ordinated alcohol or alkoxy group upon the carbonyl of a co-ordinated ester or amide. Many Lewis acidic metal ions have been shown to be effective catalysts for transesterification reactions for example, heating diethyl picolinate with copper(n) salts in methanol results in rapid and clean transesterification (Fig. 5-86). In the absence of the metal ion, the rate of reaction is vanishingly slow. 

Lee, Y., and Sayre, L. M., 1995, Model studies on the quinone-containing copper amine oxidases unambiguous demonstration of a transamination mechanism, J. Amer. Chem. Soc. 117 11823nll828. 

The postulated catalytic mechanism of amine oxidases starts from the qui-none form of the cofactor (Fig. 17). The distal oxygen atom is replaced by an amino group in a transamination reaction. The amine is then re-oxidized by molecular oxygen to the original quinone. The copper ion is not involved directly in catalysis but is only a cofactor in the synthesis of TOPA quinone (Fig. 18). 

In work aimed at elucidating the mode of pyridoxal mediated dephosphonylation of a-aminophosphonic acids, it was found that simple aminophosphonates reacted with pyridoxal to form Schiff bases, which complexed copper(II) ions, but did not react further. In contrast, o-hydroxyphenylphosphaglycine did react with pyridoxal at 40 °C with the formation of pyridoxamine, along with o-hydroxybenzoylphosphonic acid on the one hand (equation 45), and salicylaldehyde and H3PO4 (not shown) on the other. Apparently, the presence of the -hydroxy group is necessary for the success of the reaction, presumably by complexing the copper ion in the fashion indicated. The formation of 6>-hydroxybenzoylphosphonic acid illustrates the capability of a-aminophosphonic acids to participate in transamination (similarly to amino acids), while salicylaldehyde is the result of dephosphonylation (analogous to decarboxylation). 

Copper amine oxidase (CAO) enzymes carry out the aerobic oxidation of primary amines to aldehydes (Scheme 14.8a). While copper is present in the active site, substrate oxidation proceeds by an organocatalytic pathway involving an o-quinone cofactor via a transamination mechanism (Scheme 14.8b). 

It is worth noting that nickel(II) and copper(II) complexes of L193-L195 with seven- to nine-membered chelate rings undergo transamination processes when... 

In 2009, a simple and practical copper-catalyzed method for the synthesis of 1,2,4-benzothiadiazine 1,1-dioxide derivatives was developed. " The reaction proceeded via cascade reactions of substituted 2-halobenzenesulfo-namides with amidines, and the corresponding products were formed in good yields (Scheme 3.75). The reaction was proposed to start with C-N coupling then intramolecular transamination to release ammonia and provide the final product. Later on, a procedure for the synthesis of the same products via intramolecular cyclization of o-bromoarylsulfonylated amidines was developed as well. ... 

Tyrosine transaminase was purified about a hundredfold from acetone powder extracts of dog liver (the most potent source of the enzyme) by dialysis and alcohol fractionation. The presence of a phenolic hydroxyl, an alpha amino, and an alpha carboxyl group were required for a compound to be active as a substrate in this transamination system. Only the L-amino acid was attacked and the only effective keto acid is a-ketoglutaric acid. The enzyme, as would be anticipated, required pyridoxal pho hate as a coenz3rme. It contiuns copper but this apparently is unrelated to its... 

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