Alanine acid-base reactions

Interestingly, alanine and other amino acids exist primarily in a doubly charged form called a zwitterion rather than in the uncharged form. The zwit-terion form arises because amino acids have both acidic and basic sites within the same molecule and therefore undergo an internal acid-base reaction. 

Both enantiomers of A -acetyl alanine have a free carboxy group that can react with an amine in an acid-base reaction. If a chiral amine is used, such as (/ )-a-methyibenzyiamine, the two salts formed are diastereomers, not enantiomers. Diastereomers can be physically separated from each other, so the compound that converts enantiomers into diastereomers is called a resolving agent. Either enantiomer of the resolving agent can be used. 

Step [1] is just an acid-base reaction in which the racemic mixture of A -acetyl alanines reacts with the same enantiomer of the resolving agent, in this case (7 )-methylbenzylamine. The salts that form are diastereomers, not enantiomers, because they have the same configuration about one stereogenic center, but the opposite configuration about the other stereogenic center. 

Amino acids are bifunctional in that they contain both basic (amino) and acidic (carboxyl) groups. These groups undergo an intramolecular acid-base reaction to give structural formula (B), which is the better representation of alanine. 

A combination of D-amino acid oxidase and L-amino transferase is an example of a deracemization by stereoinversion. The product is an L-amino acid. The reaction catalyzed by amino transferase has an equilibrium constant close to unity, a very unpractical situation leading to uncomplete transformation and to the production of almost inseparable mixtures of amino acids (at least two, the amino acid product and the amino add used as an amino donor). For preparative purposes it is therefore mandatory to shift the equihbrium to the product side. A recent example of a deracemization procedure based on this coupled enzymatic system is the preparation of L-2-naphthyl-alanine 6 as illustrated in Scheme 13.9 [28]. The reaction occurs in one pot with initial oxidation of the D-amino acid catalyzed by D-amino acid oxidase from Rhodotonda gracilis. The hydrogen peroxide that is formed in stoichiometric amounts is decomposed by catalase. The a-keto add is the substrate for L-aspartate amino transferase (L-Asp amino transferase), which is able to use L-cysteine sulfinic acid 7 as an amino donor. 

The reduction of the pyrimidine to dihydropyrimidine is the reverse of the oxidation reaction carried out by DHODs. The structure of the FMN/pyrimidine-binding site is very similar to the structure of L. lactis DHODs. Three Asn residues form hydrogen bonds with the nitrogens and carbonyls of the pyrimidine analogous to DHODs. DPD has an active site cysteine proposed to act in acid/base chemistry similar to Class 1 DHODs. When mutated to alanine, only 1% of the wild-type activity was retained, indicating the importance of this residue in catalysis. Secondary tritium isotope effects using 5- H-uracil were determined in both H2O and D2O an inverse isotope effect was observed in H2O and the value became more inverse in D20. " This was taken as evidence of a stepwise mechanism in which hydride transfer to C6 is followed by protonation at C5. 

Kobayashi et al. also applied the catalyst to asymmetric 1,4-addition reactions of azlactones with acrylates [66]. The active a-proton of the azlactone (5(4H)-oxazolone) skeleton showed a low pKa value compared to that of the alanine Schiff bases, because the anion formed is stabilized via enol formation and aromatization. After 1,4-addition reactions with acrylates, the 2-substituted glutamic acid derivatives formed could be obtained via hydrolysis using a weak acid. It was found that Pybox 3 prepared from alaninol derivatives was effective for this reaction. The desired products were obtained in good yields with good enantios-electivities. Several amino acid derivatives containing aUcyl chains in the a-position were screened, and the leucine derivative (R = Bu) showed the best enantio-selectivity in this reaction (Table 16, entry 8). 

Simple esters cannot be allylated with allyl acetates, but the Schiff base 109 derived from o -amino acid esters such as glycine or alanine is allylated with allyl acetate. In this way. the o-allyl-a-amino acid 110 can be prepared after hydrolysis[34]. The Q-allyl-o-aminophosphonate 112 is prepared by allylation of the Schiff base 111 of diethyl aminomethylphosphonates. [35,36]. Asymmetric synthesis in this reaction using the (+ )-A, jV-dicyclohex-ylsulfamoylisobornyl alcohol ester of glycine and DIOP as a chiral ligand achieved 99% ec[72]. 

Interaction of Ni11 ions with amino acids is also important for asymmetric synthesis of amino acids. A convenient large-scale asymmetric synthesis of enantiometrically pure trans-cinnamyl-glycine and -o-alanine via reaction of cinnamyl halides with Ni11 complexes of a chiral Schiff base of glycine and alanine has been elaborated.1711 Similar procedures have been applied to other amino acids as well.1712... 

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