6-Hydroxynicotinic acid, from nicotinic

Little is known about the hydroxylation of hetoocyclic substrates, and more experimental work is needed in this area. Achromobacter xylosoxydans (DSM 2783) wad Pseudonumas pudda (NCIB 8176 or 10521) are particularly effective in the hydroxylation of nicotinic acid (107) to 6-hydroxynicotinic acid (108 equation 39), and commercial processes oqrable of giving up to 97% yield have been developed. It is interesting to note that in this case the product is precipitated as it forms by formation of its magnesium or barium salt, and this could serve to protect the product from further degradation as well as facilitating its recovery. 

Regioselective hydroxylation of aromatic compounds can also be achieved by using whole cells. For instance, 6-hydroxynicotinic acid (35) is produced industrially from nicotinic acid (34) by a Pseudomonas or Bacillus sp (equation 48) . Racemic prenalterol (37) has been obtained by regioselective p-hydroxylation of ( )-l-isopropylamino-3-phenoxypropan-2-ol (36) using Cunninghamella echinulata (equation 49) . 

The 3,6-diposition-substituted pyridine compounds are important intermediates for industrial synthesis, especially for production of some agricultural chemicals. This compound can be obtained by chemically synthesized from pyridine, but the process is accompanied by some by-products. Microbial hydroxylation of aromatic compounds is a very efficient method of regioselective reaction. Several methods have been reported for the preparation of 3,6-disubstituted pyridine using microorganisms. In 1985, Lehky et al. reported the microbial production of 6-hydroxynicotinic acid (6-HNA) from nicotinic acid (NA) by Achromobacter xylosoxydans Nagasawa et al. also prepared 6-HNA from NA by using Pseudomonas fluorescens TN5. 

The degradation of nicotine has been examined extensively in Arthrobacter nicotinovorans (oxydans) in which it is mediated by a plasmid (Brandsch et al. 1982 Schenk et al. 1998). In strain P34, the hrst metabolite was 6-hydroxynicotine, and experiments with 02 and H2 0 showed that the oxygen in the hydroxyl group was derived from H2O (Hochstein and Dalton 1965). Nicotine dehydrogenase has a molecular mass of 120,000 and contains FAD, Mo, Fe, and acid-labile sulfur (Freudenberg et al. 1988). Degradation involves a series of reactions ... 

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