6- Hydroxynicotinate

B. 6-Hydroxynicotinic acid. In a 500-ml. beaker provided with a thermometer, magnetic stirring, and external cooling is placed 117 ml. of 14% ammonium hydroxide. With stirring. 

The procedure for preparing 6-hydroxynicotinic acid is also based on a method described by von Pechmann. 6-Hydroxynico-tinic acid has also been prepared by decarboxylation of 6-hy-droxy-2,3-pyridinedicarboxylic acid by heating 6-hydra-zinonicotinic acid or its hydrazide with hydrochloric acid by the action of carbon dioxide on the sodium salt of a-pyridone at 180-200 and 20 atmospheres by heating the nitrile of 6-chlo-ronicotinic acid with alcoholic sodium hydroxide or hydrochloric acid from 6-aminonicotinic acid and by the prolonged action of concentrated ammonium hydroxide on methyl cou-malate. ... 

The degradation of nicotine has been examined extensively in Arthrobacternicotinovorans (oxydans). In strain P34, the first metabolite was 6-hydroxynicotine, and experiments with 62 and H2 0 showed that the oxygen in the hydroxyl group was derived from H2O (Hochstein and Dalton 1965). 

Dai VD, KDecker, H Sund (1968) Purification and properties of L-6-hydroxynicotine oxidase. Eur J Biochem 4 95-102. 

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 ... 

Hirschberg R, JC Ensign (1971a) Oxidation of nicotinic acid by a Bacillus species source of oxygen atoms for hydroxylation of nicotinic acid and 6-hydroxynicotinic acid. J Bacterial 108 757-759. 

Nagel M, JR Andreesen (1990) Purification and characterization of the molybdoenzymes nicotinate dehydrogenase and 6-hydroxynicotinate dehydrogenase from Bacillus niacini. Arch Microbiol 154 605-613. 

Hydroxynicotinic acid, hi82 Hydroxynitroanilines, a238, a239, a240... 

The hydroxylation of aromatic compounds using microorganisms is more predictable and a number of processes have been adapted to large scale, for example the preparation of 6-hydroxynicotinic acid1781 and (R)-2-(4-hydroxy-phenoxy)propanoic acid1791, important intermediates to pesticides and herbicides respectively. 

This enzyme [EC 1.3.7.1], also referred to as 6-oxotetra-hydronicotinate dehydrogenase, catalyzes the reaction of l,4,5,6-tetrahydro-6-oxonicotinate with oxidized fer-redoxin to produce 6-hydroxynicotinate and the reduced ferredoxin. 

This enzyme [EC 1.5.1.13], also known as nicotinate hydroxylase, catalyzes the reaction of nicotinate with NADP+ and water to produce 6-hydroxynicotinate and NADPH. This iron-dependent flavoprotein will also oxidize NADPH. 

HYDROXYNICOTINATE REDUCTASE a-KETOBUTYRATE SYNTHASE a-KETOGLUTARATE SYNTHASE... 

Substituted nicotinic acid derivatives are useful in the synthesis of pesticides and pharmaceuticals as specific inhibitors of NAD and/or NADP dependent enzymes. 6-Hydroxynicotinic acid is a very useful intermediate in the synthesis of such inhibitors. 

A range of different products is possible, all from the key 6-hydroxynicotinic acid precursor for instance via chlorination of the hydroxyl or carboxyl groups of the 6-hydroxynicotinic acid. 

Achromobacter xylosoxydans has been used to cany out the selective hydroxylation in high yield, using the enzyme which catalyses the first step in nicotinic acid degradation. The whole-cell biotransformation process has been scaled-up to 12 m, which is sufficient to produce high purity 6-hydroxynicotinic acid for the subsequent chemical reactions. The hydroxylation is oxygen requiring, so that oxygen transfer rate-limits the reaction. 

Product (R)- Glycidyl butanoate Oxamniquine L-PAC Acrylamide 6- Hydroxynicotinic acid ... 

Hydroxynicotinic acid, hi 76 a-Hydroxy-a -phenylacetophenone, b46 3-(p-Hydroxyphenyl)alanine, t437... 

Conversion of the derived methyl coumalate into methyl 6-hydroxy-nicotinate (Expt 8.35) is effected by the action of concentrated aqueous ammonia subsequent hydrolysis with aqueous alkali yields 6-hydroxynicotinic acid. 

A practical synthesis of furopyridine (49), a fragment of a HIV-protease inhibitor, was accomplished starting with 6-hydroxynicotinic acid <95TL(36)4571>. Nevirapine (50), and its derivatives, have received much attention because of their inhibition of reverse transcriptase in HIV-type 1 <95JMC(38)4830> <95JMC(38)4839>. (50) has been synthesized using a directed metallation approach <95JOC(60)1875> <95H(41)753>. 

For the direct hydroxylation of N-heterocycles a microbial oxidation is most suitable. Lonza developed a process to produce 6-hydroxynicotinic acid on a 10 tonnes scale [5]. The enzymatic production is carried out in two-steps. Firstly, Achromobacter xylosoxydans LK1 biomass is produced, which possesses a highly... 

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