Reduction transamination

A modified protocol of the Eschweiler-Clarke reaction, a reductive transamination, was also used for an efficient N-alkylation of hexahydroazepine and benzylamine in the presence of formic acid and aldehydes or ketones53. 

While kinetic resolution with the help of lipases or esterases has seen the greatest success for the synthesis of enantiomerically pure amines, the same target can be reached by employing co-transaminases (co-TA) to reductively transaminate ketones to either (S)- or (K)-amines, depending on the transaminase. The reaction is shown in Figure 7.22 with acetophenone and (S)-transaminase as an example (Shin, 1998, 1999). 

Gobolos, S., Tfirst, E., Margitfalvi, J., Hayes, K.S. (1999) Asymmetric synthesis of (S)-alkylamines via reductive transamination of ketones over carbon-supported Palladium catalysts, J. Mol Catal A. Chem. 146, 129-138. 

The investigation of the aminotransferase activity of apple ACS carried out by Feng et al reveals that it is able to reductively aminate PLP to PMP by transamination of some L-amino acids to their corresponding a-keto acids. The enzyme has shown substrate specificity with the preference of Ala > Arg > Phe > Asp. The addition of excess pyruvate causes a conversion of the PMP form of the enzyme back to the PLP form. The quite unstable PMP form of ACS can generate apoenzyme, which captures PLP to restore its physiologically active form. 

Several characterized NRPSs utilize alternative methods for chain termination. In some synthetases, the TE domain of the final module is replaced by an NAD(P)H-dependent reductase domain. Reduction of a peptidyl-S-PCP substrate through a two-electron reaction leads to the formation of a transient aldehyde, which is subsequently converted into a cyclic imine or hemiaminal through intramolecular cyclization. This two-electron reaction is utilized in the biosynthesis of nostocyclopeptides, the saframycins, ° and anthramycin. Alternatively, a four-electron reduction to the primary alcohol is observed in the biosynthesis of mycobacterial peptidolipids, linear gramicidin," " the myxalamides, lyngbyatoxin, " and myxochelin A 75,76 alternative four-electron reduction pathway involving aldehyde formation, transamination, and reduction to a primary amine occurs in the biosynthesis of myxochelin B. ... 

This has obvious advantages over the process seen for glutamate synthesis via the reductive amination of 2-oxoglutarate, in that it no longer requires the intervention of free ammonia. We thus have the situation that some organisms are able to carry out the fixation of ammonia via reductive amination, whereas others manipulate via transamination the amino acid structures obtained from protein in the diet. 

Essential amino acid Transamination Reductive amination... 

Scheme 6.16 TA-catalyzed transamination coupied with pyruvate reduction.

Although 2-phenylethanol can be synthesised by normal microbial metabolism, the final concentrations in the culture broth of selected microorganisms generally remain very low [110, 111] therefore, de novo synthesis cannot be a strategy for an economically viable bioprocesses. Nevertheless, the microbial production of 2-phenylethanol can be greatly increased by adding the amino acid L-phenylalanine to the medium. The commonly accepted route from l-phenylalanine to 2-phenylethanol in yeasts is by transamination of the amino acid to phenylpyruvate, decarboxylation to phenylacetaldehyde and reduction to the alcohol, first described by Ehrlich [112] and named after him (Scheme 23.8). 

TRANSAMINATION // REDUCTIVE AMINATION Aminotransferase X Glutamate dehydrogenase... 

The intermediate (32), produced upon decarboxylation of (31) may protonate at the a-carbon of the substrate (path a, Scheme 9), or at the 4 -carbon of PLP (path b). The hydrolysis of the aldimine produced by the former path accounts for the products of a-decarboxylation (equation 13). The hydrolysis of the aldimine produced in path (b) yields an aldehyde and pyridoxamine phosphate (PMP) (35). Note that this latter reaction, a decarboxylation-dependent transamination, may be classified as a redox process (reductive amination of PLP to PMP). 

The two transamination steps in the pathways may be linked, as indicated in Fig. 17-5, to form a complete cycle that parallels the citric acid cycle but in which 2-oxoglutarate is oxidized to succinate via glutamate and y-aminobutyrate. No thiamin diphosphate is required, but 2-oxoglutarate is reductively aminated to glutamate. The cycle is sometimes called the y-aminobutyrate shunt, and it plays a significant role in the overall oxidative processes of brain tissue. 

This is followed by ATP-dependent reduction to the aldehyde.2643 The final step of transamination is not accomplished in the usual way (with a PLP-dependent enzyme), but through formation of a Schiff base with glutamate and reduction to saccharopine.265 Oxidation now produces the Schiff base of lysine with 2-oxoglutarate. 

---