Glutamic acid from reductive amination

L)-Phosphinotricin 67, which is the active component of naturally occurring antibiotic biolaphos, was synthesized from the corresponding keto acid 66 via reductive amination catalysed by L-glutamate dehydrogenase (EDH) (Equation 32)7 ... 

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. 

In bacteria and plants, glutamate is produced from glutamine in a reaction catalyzed by glutamate synthase. a-Ketoglutarate, an intermediate of the citric acid cycle, undergoes reductive amination with glutamine as nitrogen donor ... 

L-6-Hydroxynorleucine, a different key chiral intermediate used for synthesis of the vasopeptidase inhibitor Omapatrilat (Vanlev ), was prepared in 89% yield and > 99% optical purity by reductive amination of 2-keto-6-hydroxyhexanoic acid using glutamate dehydrogenase from beefliver (Hanson, 1999) (Figure 13.22). In an alternative process, racemic 6-hydroxynorleucine produced by hydrolysis of 5-(4-hydroxybutyl)hydantoin was treated with D-amino acid oxidase to prepare a mixture containing 2-keto-6-hydroxyhexanoic acid and L-6-hydroxynorleucine followed by the reductive amination procedure to convert the mixture entirely to L-6-hydroxynorleucine, with yields of 91-97% and optical purities of > 99%. 

Other resolving agents are readily prepared from inexpensive chiral starting materials such as glucose, aspartic acid, or glutamic acid. A literature example is the use of /V-methylglucamine 6, obtained by reductive amination of D-glucose, in the resolution of naproxen (Chapter 6).13... 

The synthesis of a-amino acids has been carried out from a-keto acids by reductive aminadon using a platinum or palladium catalyst, mimicking their biosynthesis. Thus alanine, leucine, phenylalanine, " aspartic acid and glutamic acid - have been synthesized by reductive amination. When an optically active primary amine is used, asymmetric induction can proceed in the course of the reductive amination. 

The proposed biosynthesis of piperazate residue of kutznerides, in analogy with monamycin and polyoxypeptin biosynthesis [213, 214], starts from the precursors glutamic acid and glutamine. The N—bond formation is achieved by the initial A-hydroxylation catalyzed by Ktzl, followed by the intramolecular displacement of the hydroxyl group by 5-amine as a nucleophile. The y,5-deidropiperazate is the common intermediate for all four piperazate moieties in kutznerides. Tautomerization of enamine to imine forms the -N unsaturated dehydropiperazate. Reduction of hydrazone leads to piperazate. The biosynthesis of y-chloro-substituted piperazate... 

More specific labelling may be obtained in a biosynthetic process using enzymic methods of synthesis. The preparation of amino acids by the reductive amination of 2-keto acids is well known. Indeed, the synthesis of N-labelled amino acids by this route is among the earliest literature on the preparation of compounds labelled with stable isotopes [73], Such reductions can be carried out enzymically and L - [a- N] glutamic acid has been prepared in good yield from 2-oxoglutaric acid and N-labelled ammonium chloride in the presence of reduced nicotinamide adenine dinucleotide phosphate [74],... 

Due to the mild conditions and tolerance for a variety of functional groups, the method has become widely used in the synthesis of N-protected amino aldehydes (Scheme 22). a-Amino aldehydes (32) are prepared with no epimerization.t Hss] jjj jjjg eduction of 33 and 34 the intermediate aldehydes are converted directly to the diene 35 or amine 36,respectively, as a through process. In the reduction of 37 and 38 the benzyl thioester was used in place of the ethyl thioester. jS-Amino aldehydes can be prepared from the aspartic acid derivatives 39 and 40. " Similarly, the glutamic acid derivative 41 is converted cleanly to y-aminoaldehyde.f In one example the method was used... 

Pyrrolidinone derivatives can be useful synthons. Ethyl pyroglutamate (75), derived from L-glutamic acid (see chapter five, section S.l.C.ii), was converted to cyanomethyl-2-pyrrolidinone 6.14 Reduction to the amine l and Cope elimina-tionl2 gave 6.1S, which was hydrolyzed to 4-aminohex-5-enoic acid (6.16), also an... 

Hydroxy-lactone 6.75 was prepared in several steps from glutamic acid (see chapter 2, section 2.2) and then opened by treatment with iodotrimethylsilane to give 6.76.Displacement of iodide with sodium azide, followed by reduction to the amine and hydrolysis, gave R-GABOB in 56% overall yield (>99%ee). 

Glutamic acid is the central product of reductive amination. Transamination from glutamic acid to a-keto acids leads to the formation of... 

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