Amino acids reductive animation

The nutrient sparing effect of antibiotics may result from reduction or elimination of bacteria competing for consumed and available nutrients. It is also recognized that certain bacteria synthesize vitamins (qv), amino acids (qv), or proteins that may be utilized by the host animal. Support of this mode of action is found in the observed nutritional interactions with subtherapeutic use of antibiotics in animal feeds. Protein concentration and digestibiHty, and amino acid composition of consumed proteins may all influence the magnitude of response to feeding antibiotics. Positive effects appear to be largest... 

Reductive animations also occur in various biological pathways, fn the biosynthesis of the amino acid proline, for instance, glutamate 5-semjaldehyde undergoes internal imine formation to give 1-pyrrolinium 5-carboxylate, which is then reduced by nucleophilic addition of hydride ion to the C=N bond. 

Show how you could prepare the following amino acids using a reductive animation ... 

Reductive animation, 930-932 amino acid synthesis and, 1026 biological example of, 932 mechanism of, 931 Refining (petroleum). 99-100 Regiospecific, 191... 

Another route to the formation of piperidine heterocycles is cyclization via reductive animation utilizing various hydride sources. The scheme below depicts a bis reductive animation, using sodium triacetoxyborohydride as the hydride source, to generate exo-178 and endo-179 azabicyclo[3.2.1]octane amino acids in moderate yields <06JOC8467>. 

The highly enantioselective reductive animation of a-keto acids as a route to amino acids is possible with ligand 118 (3 R,4R)- l-W-benzyl)-3,4-bis(diphenylphosphanyl)pyrrolidine, DEGUPHOS] and [Rh(cod)2]BF4.649 (R,R)-NORPHOS (2-exo-3-endo-bis(diphenylphosphino)bicyclo[2.2.1 ]heptene) and (2. S, 3. S ) - C HIR AP H O S (bis(diphenylphosphino)butane) are also good ligands for this transformation. Arylpyruvic acids give the best results (>95% ee). 

Aminotransferases are widely distributed enzymes in nature, participating in a number of metabolic pathways (7-11). They catalyze the transfer of an amino group originating from an amino acid donor to a 2-ketoacid acceptor. In effect, this statement implies the reductive animation of a keto moiety, although a redox process is not directly involved. 

Fluoro amino acids have been incorporated into peptides, in order to ease the transport or reduce the systemic toxicity. Thus, trifluoroalanine, a powerful inhibitor of alanine racemase, is an essential enzyme for the biosynthesis of the cell wall of bacteria. It has a low antibiotic activity because of its very poor transport. In order to facilitate this transport, the amino acid has been incorporated into a peptide. This delivery allows a reduction of the doses, and thus the toxicity of the treatment is lowered.3-FIuorophenylaIanine (3-F-Phe) is a substrate of phenylalanine hydroxylase, which transforms it into 3-F-Tyr. 3-F-Tyr has a high toxicity for animals, due to its ultimate metabolization into fluorocitrate, a powerful inhibitor of the Krebs cycle (cf. Chapter 7). 3-F-Phe has a low toxicicity toward fungus cells, but when delivered as a tripeptide 3-F-Phe becomes an efficient inhibitor of the growth of Candida albicans. This tripeptide goes into the cell by means of the active transport system of peptides, where the peptidases set free the 3-F-Phe. ... 

The amino acid (S)-tert-leucine (48) has been shown to be an important intermediate for a wide variety of pharmaceutically active molecules in the areas of antitumor, anti-inflammatory, and antiviral activity [42]. A number of routes to (S)-tert-leucine (48) have been developed, in particular the aqueous-based process from Degussa using asymmetric reductive animation of the prochiral keto acid with dehydrogenase and factor recycling [43, 44]. An industrial alternative was... 

The 20 amino acids listed in Table 27.1 are biosynthesized by a number of different pathways, and we will touch on only a few of them in an introductory way. We will examine the biosynthesis of glutamic acid first because it illustrates a biochemical process analogous to a reaction we discussed earlier in the context of amine synthesis, reductive animation (Section 22.10). 

Use of benzyl alcohol resulted in formation of the benzyl ether corresponding to allyl ethers 52, but attempted Claisen rearrangement resulted in an 82 % yield of the product of a 1,3-benzyl shift (see Section 5.1.3.).20 To demonstrate the utility of the methodology outlined in Table 14, x-oxoester 53a was converted into the corresponding x-amino acid by hydrolysis and reductive animation.20... 

Microwave-induced imine formation, subsequent reduction with NaBH(OAc)3 and cyclisation of the resulting amino acid with isothiocyanates was used in an efficient one-pot multi-step synthesis of thiohydantoins (Scheme 4.26). The reductive animation was conducted as a two-step procedure to avoid direct reduction of the aldehyde at high temperatures48. 

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