Large-scale pharma intermediates

Enzymatic processes also advance in the area of large-scale pharma intermediates /flactam antibiotics can now be produced in a fully biotechnological process, including the semi-synthesis from the /flactam core to the penicillin or cephalosporin. A precursor to ephedrine, long produced by a whole-cell process in yeast, can be obtained from benzaldehyde and acetaldehyde with the help of pyruvate dehydrogenase acting as a carboligase. 

About one tenth of the total amount of vitamin E produced is semi-synthetic, isomerically pure (2R,4 K,8 R)-a-tocopherol (RRR-3) which is used almost exclusively in human applications (mainly pharma). This product, originating from natural sources, is obtained from soya deodorizer distillates (SDD). Vegetable oils refined on a large scale are the major sources of vitamin E compounds [26-28]. The deodorizer distillate, originally a waste stream, contains considerable amounts (up to 10%) of a-, [I-, y- and b-tocopherols (RRR-3 to RRR-6) which are isolated by several separation methods. To increase the value of the vitamin E concentrate of mixed tocopherols obtained from SDD, the lower (I-, y- and d-homologues (RRR-4 to RRR-6, content ca. 90%) have to be transformed subsequently into the biologically more active a-tocopherol (RRR-3, only ca. 5% in the original mixture) by permethylation reactions. Permethylations are performed by chloro-, amino-, or hydroxymethylation reactions to provide functionalized alkylated intermediates, which are reductively converted into RRR-3 (Fig. 3) [29]. 

Enzymatic processes are important in the areas of erop protection and pharma intermediates too. Technical improvements can result directly from immobilization (e. g. increased product purity and/or yield, reduced waste production) but also indirectly. Immobilization of cells or enzymes enables the use of eontinuous rather than batch operation, thus simplifying process control and reducing labor costs. Of course, this is only advantageous for large-scale processes, whereas most bioproducts are only produced on a small scale. 

---