Pathway quinoline

It was discovered in 1998 that expression of IDO activity in the mouse fetus represses the maternal T-cell activity and hence protects the fetus from the maternal immune system. Pregnant mice treated with the IDO inhibitor 1-methyltryptophan rejected the embryos via their immune system, thus either IDO itself or a product of tryptophan catabolism is able to suppress the maternal T-cell activity. IDO is also expressed in response to interferon 7 from activating T-cells, inhibiting T-cell proliferation and contributing toward the antiviral activity of interferon 7. The end product of the L-tryptophan degradation pathway, quinolinic acid, has neurological effects, hence the IDO pathway is implicated in several mammalian regulatory pathways. 

In the reaction of quinoline W-oxide with 1-phenylbenzimidazole, 2,2 -biquinoline derivative was isolated as a side product. In order to examine the reaction pathway, quinoline W-oxide was allowed to react without 1-phenylbenzimidazole. Quinoline A-oxide was treated with TMAF and dimethylaminosilane at room temperature, and 2,2-biquinoline W-oxide was obtained in 40% yield. On the other hand, the same reaction at 120 °C gave deoxygenated 2,2-biquinoline, which was obtained in 70%... 

Conra.d-Limpa.ch-KnorrSynthesis. When a P-keto ester is the carbonyl component of these pathways, two products are possible, and the regiochemistry can be optimized. Aniline reacts with ethyl acetoacetate below 100°C to form 3-anilinocrotonate (14), which is converted to 4-hydroxy-2-methylquinoline [607-67-0] by placing it in a preheated environment at 250°C. If the initial reaction takes place at 160°C, acetoacetanilide (15) forms and can be cyclized with concentrated sulfuric acid to 2-hydroxy-4-methylquinoline [607-66-9] (49). This example of kinetic vs thermodynamic control has been employed in the synthesis of many quinoline derivatives. They are useful as intermediates for the synthesis of chemotherapeutic agents (see Chemotherapeuticsanticancer). 

The kynurenine pathway metabolites are kynurenine, kynurenic acid, xahthurenic acid, 3-hydroxykynurenine, anthranilic acid and quinolinic acid. The more important are kynurenine (Kyn) and 3-hydroxykynurenine (30HKyn) (Fig 1). 

When iV-substituted acylanilides 9 are treated under the same reaction conditions, the corresponding lV-substituted-2-quinolones 10 are isolated in high yields. This reaction was initially misinterpreted, but it has since been demonstrated to follow a similar mechanistic pathway to the Meth-Cohn quinoline synthesis. ... 

Pathways and biocatalysts of bacterial degradation quinolines 98AG(E)577. 

A bacterial strain BN6 oxidizes 5-aminonaphthalene-2-sulfonate by established pathways to 6-amino-2-hydroxybenzalpyruvate that undergoes spontaneous cyclization to 5-hydroxy-quinoline-2-carboxylate (Figure 2.2a) (Nortemann et al. 1993). 

Benzothiophene is isoelectronic with naphthalene, dibenzothiophene with anthracene, and benzothiazole with quinoline, and this is reflected in their aerobic degradation that is initiated by dioxygenation. The diversity of pathways for the degradation of dibenzothiophene is illustrated by the following examples ... 

Figure 1 Proposed reaction pathways for the hydrogenation of quinoline (a = 1,2-dihydroquinoline, b = 1,4-dihydroquinoline, c = 3,4-dihydroquinoline).

The most broadly studied organic nitrogen compound is probably quinoline however, most studies report biodegradation. As we have seen from Table 14, quinoline is representative of the organonitrogen compounds present in the diesel cut. Its transformation has been studied in both, anaerobic and aerobic conditions. Several metabolic pathways have been proposed to explain the aerobic transformations however, no pathway has been proposed for quinoline metabolism under anaerobic conditions. 

Figure 19. Suggested partial pathway for the degradation of quinoline P. ayucida IGTN9m.

It was specifically stated that the proposed metabolic pathway, which suggest C—N bond cleaving and so, a N-specific mechanism, was found when PTA-806 was employed as the biocatalyst. However, when the quinoline-adapted microorganisms, initially isolated from the chemostats (the native P. ayucida), were tested, they were found to fully degrade quinoline, utilizing it as both, a carbon as well as a nitrogen source. 

Further transformation included additional hydroxylation steps leading to 2,6-dihydroxyquinoline and a trihydroxyquinoline (probably 2,5,6-trihydroxyquinoline). Shukla [322], working with Pseudomonas sp. identified an alternate pathway, involving additional metabolites, besides the 2-hydroxyquinoline and 8-hydroxycoumarin. These were 2,8-dihydroxyquinoline and 2,3-dihydroxyphenylpropionic acid. Quinoline-adapted cells were also able to transform 2-hydroxyquinoline and 8-hydroxycoumarin without a lag phase, providing additional support for their intermediate role as intermediates in the metabolism of quinoline. 

Schwarz et al. in agreement with Shukla observed the formation of 2-Oxo-l, 2-dihydroquinoline, 8-hydroxy-2-oxo-l, 2-dihydroquinoline, 8-hydroxycoumarin, and 2,3-dihydroxy-phenylpropionic acid were found as intermediates of quinoline transformation by P. fluorescens 3 and P. putida 86 [325], They compared that metabolic pathway with the one obtained for Rhodococcus strain B1 (Fig. 22). This bacterium was unable to yield denitrogenated metabolites (i.e., 2-oxo-l, 2-dihydroquinoline, 6-hydroxy-2-oxo-l, 2-dihydroquinoline, and 5-hydroxy-6-(3-carboxy-3-oxopropenyl)-lH-2-pyridone). 

The systematic work carried out by Fetzner group with enzymatic catalysis resulted in the identification of four pathways of aerobic degradation of quinoline (and its derivatives) [326], shown in Fig. 23. The four pathways are named on the basis of the metabolic intermediates identified in the respective pathways, some steps and reactions have been considered in previously described pathways, but are included here to show the comprehensive nature of this work. 

Figure 22. Proposed pathway for the transformation of quinoline by Rhodococcus strain Bl.

As can be seen, in both the 5,6- and the 7,8-dihydroxy-2(lH)quinolinone pathways, after initial hydroxylation adjacent to the N-heteroatom, the benzene moiety of the quinoline ring is transformed to a dihydroxy derivative 5,6- or 7,8-, respectively, which subsequently undergoes ring cleavage. However, neither of them involves C—N bond cleavage and consequently do not lead to denitrogenated products. 

The metabolites identified [327] for each of these pathways are collected in Table 15 and once again, it should be emphasized that only the last two, catechol/anthranilate and coumarin pathways (named c and d, in Fig. 23) yield denitrogenated products. In summary, the four metabolic pathways identified for quinoline transformation, as shown in Fig. 23, are ... 

The proposed pathways for methyl-substituted quinolines differ from those shown in Fig. 23, even for the same culture, and most particularly, the fact that no C—N bond cleavage has been observed in most of the strains. A limited number of methylquinolines can be hydroxylated due to the inhibiting and blocking effect of the methyl group, particularly at position 2. So, neither P. aeruginosa QP nor P. putida QP could metabolize 2-methylquinoline however, a new strain of Pseudomonas (MQP) isolated by Grant and Al-Najjar [328] was reported to be able to transform 2-methylquinoline, yielding... 

Some of the enzymes involved in the known pathways for the degradation of quinoline have been isolated and purified. However, not all enzymes have been identified, or characterized. In this section, we will consider the enzymes associated with the degradation of quinoline (and related compounds), carbazole and indole. To examine the enzymatic work, the reader is referred to the previous section, in which the metabolic pathways were detailed. 

In summary, we may add that bacterial utilization of quinoline and its derivatives as a rule depends on the availability of traces of molybdate in the culture medium [363], In contrast, growth of the bacterial strains on the first intermediate of each catabolic pathway, namely, the lH-2-oxo or 1 II-4-oxo derivatives of the quinoline compound was not affected by the availability of molybdate. This observation indicated a possible role of the trace element molybdenum in the initial hydroxylation at C2. In enzymes, Mo occurs as part of the redox-active co-factor, and all the Mo-enzymes involved in N-heteroatomic compound metabolism, contain a pterin Mo co-factor. The catalyzed reaction involves the transfer of an oxygen atom to or from a substrate molecule in a two-electron redox reaction. The oxygen is supplied by the aqueous solvent. Certainly, the Mo-enzymes play an important role in the initial steps of N-containing heterocycles degradation. 

C. tetosteroni 63 [320,349] Susanne Fetzner Quinoline 2-oxidoreductase (360 kDa) Nitrogen removal (hydroxycoumarin pathway). Reactivity demonstrated with heterocyclic-N... 

Shukla [323] isolated an aerobic Gram-negative motile bacterium from sewage which was identified as a P. stutzeri and was found to degrade quinoline by a different pathway, yielding denitrogenated products. 

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