A-Aminophenylacetic acid

The next type of semisynthetic penicillins are those in which the acyl group is represented by an amino acid, mainly a-aminophenylacetic acid (phenylglycine) or p-oxy-a-aminophenylacetic acid, and correspondingly, ampicillin and amoxicillin. 

By combining a-aminophenylacetic acid with d-camphorsulphonic acid Betti and Mayer in 1908 separated it into its isomers. This seems to be the first case in which the basic function of an amino acid has been requisitioned for purposes of separation in all the above cases, the acidic function, by combination with optically active bases, has been made use of... 

AMINO-4-OTTI10PHENOL, 25, 5 2-Amino-5-nitrotoluene, 20, 73 22,44 d/-a-AMINOPHENYLACETIC ACID, 22, 23 (fl-a-AatINO-a-PHENYLPROPIONIC ACID,... 

The decarboxylative acylation of a-aminophenylacetic acid in refluxing acetic anhydride alone gives about 20% yield of 2,5-dimethyl-4-phenyloxazole and a similar amount of uncyclized a-acetamido-a-phenylacetone.66 2-Vinyl- and 2-isopropenyl-4,5-dimethyloxazoles have been prepared in good yields by the Dakin-West reaction of JV-acryloyl-and JV-methacryloyl-a-alanine, respectively, followed by cyclization of the oxoamides in PPA at 140°C for 4 hours,66 67... 

The 2-arylidenepseudoxazolones are generally prepared by cycliza-tion of W-(a-halophenylacetyl)-a-amino acids.99,100 Thus, 2-phenyl-methylene-4-phenyl-3-oxazolin-5-one (35) was obtained by treating N-(a-chlorophenylacetyl)-a-aminophenylacetic acid (34) with acetic anhydride99 or from the more accessible N-mandeloyl-a-ami nophenyl-acetic acid (33) and acetyl chloride100 [Eq. (16)1, presumably via the unstable chlorooxazolone, which rapidly loses hydrogen chloride. 

As indicated above, the reaction catalyzed by the general d- and l-amino acid oxidases has been represented by a dehydrogenation of an amino acid by a flavoenzyme to jneld reduced flavoenzyme and the corresponding imino acid [reactions (2) - - (4)]. Indirect support for the formation of the hypothetical imino acid has been provided by a number of studies which exclude a,/3-unsaturation in the course of the reaction. For example, it has been shown that (a) the four isomers of isoleucine are enzymically oxidized by the appropriate amino acid oxidase to the corresponding optically active a-keto-/3-methylvaleric acids (5, 6), (b) the l-isomers of /3-phenylserine are converted by L-amino acid oxidase to the respective isomers of mandelic acid (7), (c) the l- and D-isomers of a-aminophenylacetic acid, which have no /3-hydrogen atom, are attacked by the amino acid oxidases 8, 9), aod (d) on the oxidation of L-leucine in the presence of D,0 by L-amino acid oxidase, no deuterium is found in the isolated a-ketoisocaproic acid (10). More direct evidence for the formation of the a-imino acid as an intermediate has been provided by Pitt (10a) in studies on the oxidation of aromatic amino aci by ophto-n-amino acid oxidase in the presence of a tautomerase. 

A similar series of reactions with the corresponding hexenoic acid derivative was used for the demonstration that (-)-)norleucine is related to n(+)aspartic acid (Karrer and Itschner, 1936). The configuration of (-l-)a-aminophenylacetic acid, which behaves like an L-amino acid in physical and biological respects, has also been proved by chemical... 

If the methyl group of polymer 3 was replaced by a carbonyl group as in polymer 6 (6 obtained by reacting polystyrenesulfochloride with D-a-aminophenylacetic acid) the resolution efficiency for DL-mandelic acid was improved distinctly (see Table II). 

In most cases polysalt formation can be excluded in examining the reason for the obtained resolutions, as most polymers can only bind basic racemic mixtures as salts. A reasonable explanation for the partial resolution of DL-mandelic acid (I) might be the formation of diastereomeric adsorbates. Also it seems that the resolution of DL-a-aminophenylacetic acid (VII) does not proceed via salt formation mainly. 

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