Regioselective microbial oxidation

Table 7 Regioselective Microbial Oxidation of Bile Acids ...

Lonza, for example, has commercialized processes for highly chemo- and regioselective microbial ring hydroxylation and side-chain oxidation of heteroaromatics (see Fig. 2.32 for examples) (Kiener, 1995, 1999). The pharmaceutical intermediate 5-methylpyrazine-2-carboxylic acid, for example, is manufactured by microbial oxidation of 2,5-dimethylpyrazine. Many conversions of the type shown in Fig. 2.32 would not be possible by conventional chemical means. 

In some cases the regioselectivity of a microbial oxidation is governed by the absolute configuration of the substrate. For example, the racemic amide (13 Scheme 4) gives two major products upon culturing with Beauveria sulfurescens, one from hydroxylation at C-S (14 29% yield, 44% ee) and derived from the (15)-enantiomer of the substrate, and one from hydroxylation at C-4 (IS 22% yield, 53% ee) and derived from the (l/f)-enantiomer. ... 

Neither dialdehydes nor dicarboxylic acids were detected and it was shown that this microbial oxidation had excellent regioselectivity. These generated co-hydroxy aldehydes could be used as starting materials for macrocyclic musk related compounds. The yields varied depending on the substrate concentration. Lower concentrations gave better yields. However, even at 3% concentration, the conversion ratio reached about 15% and co-hydroxy aldehydes were produced at about 5g/L medium. This figure was sufficient for production. 

This process is now only of historical interest. Like the fermentation of butanol and acetone it has succumbed to advances in chemistry. However, it illustrates the other important feature of microbial transformations, which is their stereoselectivity. This, together with the regioselectivity apparent in the oxidation of sorbitol, is an important argument in favour of biological catalysis. 

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