Pyruvic acid Racemic mixture

The enzyme is a single enantiomer of a chiral molecule and binds the coenzyme and substrate m such a way that hydride is transferred exclusively to the face of the carbonyl group that leads to (5) (+) lactic acid Reduction of pyruvic acid m the absence of an enzyme however say with sodium borohydride also gives lactic acid but as a racemic mixture containing equal quantities of the R and S enantiomers... 

Figure A8.18 A racemic mixture of a-hydroxyacids (like L, D-lactate) can be transformed via the corresponding a-ketoacid (pyruvate) to the desired L-amino acid (L-alanine) with cofactor recycling.

The n-propyl derivative was used as a chiral reaction medium (ionic liquid) to react a-naphthol with ethyl pyruvate in the presence of the Lewis acid CpZrClj resulting in a racemic mixture of products (see Figure 6.21). Apparently the chiral centre in the histidine backbone of the ionic liquid has no bearing on the steric situation around the active centre of the catalytic reaction. 

Another pharmaceutical administered as a racemic mixture to treat liver diseases is a-Iipoic acid (Thioctacid). Practically nothing is known about the activity of the individual enantiomers, although naturally occur-ring (+)-a-lipoic acid has an R-configuration. The first enantiomer separation of a-lipoic acid methyl ester was demonstrated on colunms with Lipodex D (Fig. 12,46). a-Lipoic acid is involved in the oxidative decarboxylation of pyruvic add to activated acetaldehyde, which is transferred to coenz3une A to form acetyl coenzyme A. 

The above-mentioned chemical catalytic routes lead to racemic AHA mixtures. For the direct use of LA (or its esters) as a solvent or platform molecule for achiral molecules like acrylic acid and pyruvic acid, stereochemistry does not matter. The properties of the polyester PLA, the major application of LA, however, suffer tremendously if d and l isomers are built in irregularly [28]. This is exemplified by atactic PLA, made from racemic LA, which is an amorphous polymer with low performance and limited application. However, when l- and D-lactic acid are processed separately into their respective isotactic L- and d-PLA, as discovered by Tsuji et al., a stereocomplex is formed upon blending these polymers. This polymer exhibits enhanced mechanical and thermal properties [28, 164]. A productive route to D-Iactic acid is, however, missing today. If the chemocatalytic routes to LA are to become viable, enantiomer resolution of the racemate needs to be performed. Given separation success, a cheap source of o-lactic acid will be unlocked immediately, providing an additional advantage over the fermentation route (cfr. Table 2). 

Redox reactions Another way to resolve racemic mixtures is the enzyme-catalyzed oxidative transformation of the undesired enantiomer. This approach was used for the synthesis of (5)-[3-"C]valine (14). For this purpose chemically synthesized racemic [3-"C]valine was treated with immobilized (/ )-amino acid oxidase (EC 1.4.3.3). This converted the undesired (7 )-enantiomer to [3-"C]pyruvic acid (15), which could be easily removed by HPLC. (5)-[3-"C]Valine was obtained in e.e.s of 90-99%, even though reaction times were held to 17 min or less because of the 20 minute half-life of carbon-11. 

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