2-quinolone-4-carboxylic acid

With malonic acid they form 2-quinolone-4-carboxylic acids (166) by acid-catalyzed rearrangements of intermediates (165). 

Pyruvic acid and isatins gave quinoline-2,4-dicarboxylic acids.16 36 Use of malonic acid with isatins gave 2-quinolone-4-carboxylic acids.169 620 Nitromethane and isatin with 50% potassium hydroxide gave 3-nitroquinoline-4-carboxylic acid.623... 

This section reviews the results of investigations on other methods for the synthesis of 4-quinolinecarboxylic acid derivatives, including various 2-quinolone-4-carboxylic acids. The transformations were mostly based on various substituted hydroxyindoles or isatins. 

However, the ketols 166 and 167, which are similar to compounds 164 and are the products from the condensation of isatin 7 with malononitrile or phenylacetic ester respectively, were transformed into 2-quinolone-4-carboxylic acid 168 or its 3-phenyl derivative 169 [146],... 

Papers in which the reactions of isatins with various reagents leading mainly to derivatives of 2-quinolone-4-carboxylic acid were studied are discussed below. The condensation of isatins 180 with diketene gave quinolonecarboxylic acids 181 acylated at position 3 [152],... 

The described recyclization was used for the synthesis of 2-quinolone-4-carboxylic acid labeled with the 13C isotope at position 2 or 3 from the products of the acylation of isatin 7 by the acid chlorides CH313C0C1 or H313CC0C1 respectively [168],... 

A -Acetylisatin, after ring-opening by base to the a-keto carboxylate 71, undergoes an intramolecular aldol condensation producing 2-quinolone-4-carboxylic acid 72. In the same way, o-A-acylaminoaryl ketones 73 can be made to cyclize to give either 2- or 4-quinolones Camps synthesis) ... 

Application of [2- C]IAA to the cotyledon of etiolated 5-day-old broad been (Vicia faba L. cv Chukyo) seedlings resulted in accumulation of radioactive substances in the root primordia and in the stele of the basal part of the roots [24, 25]. Two metabolites being more polar than lAA-Asp accounted for 70-80% of total radioactivity in the root after 24-h treatment, and they were not extracted with ether in acid pH. After hydrolysis with 2 M HCl or 7 M NaOH, their radioactive moieties were extracted with ether, but they did not coincide with lAA. We purified the two substances from Vicia roots and identified them as 3-(0-)S-glucosyl)-2-indolone-3-acetylaspartic acid (Glc-DIA-Asp) and 3-hydroxy-2-indolone-3-acetylaspartic acid (DIA-Asp) [26, 27]. The DIA moiety is converted into 2-quinolone-4-carboxylic acid (QCA) by acid hydrolysis and the UV spectrum of QCA is quite different from that of DIA, which is in contrast with the conversion of OxIAA into l,2,3,4-tetrahydro-2-quinolone-4-carboxylic acid without accompanying large spectral change. 

In the alkaline medium, isatin is cleaved at the amide bond and converted to the salt 82 of isatinic acid, which undergoes aldol condensation with a-methylene ketones and cyclization with H2O elimination affording quinoline-4-carboxyhc acids (83). Notably, N-acetylisatins (84), after base-induced ring-opening (— -85), undergo an intramolecular aldol condensation giving rise to 2-quinolone-4-carboxylic acids (86). 

Quinolone carboxylic acids are a class of totally synthetic antibacterial agents which have the general structure (1). 

In the final stage, as depicted in Scheme 10, the BOC-protected compound 45 and the quinolone carboxylic acid 27 are heated in DMSO under tri-ethylamine, followed by deprotection of the terf-butoxycarbonyl group under acidic condition to afford the final product DQ-113 (26). 

Quinolone carboxylic acid antibacterials are synthetic compounds whose basic nuclear structure includes a quinolone ring and a carboxylic acid group. Fluoroquinolones are second-generation quinolones that contain in their molecule a fluorine and a piperazine ring. Quinolones are amphoteric compounds slightly soluble in polar solvents such as water, and insoluble in nonpolar solvents such as benzene and hexane. Most of these drugs are fluorescent and are quite stable in aqueous solution toward light, except miloxacin, which is reported to be unstable. 

Lesher GY. Nalidixic acid and other quinolone carboxylic acids. In Encyclopedia of Chemical Technology, 3rd edn. Kirk-Othmer (Ed.) John Wiley, Sons New York, Chichester, Brisbane,... 

Petersen U, et al. The synthesis and biological properties of 6-fluoro-quinolone-carboxylic acids. Bull. Chim. Soc. Belg, 1996, 105, 683-699. 

Kim WJ, et al. Novel quinolone carboxylic acid derivatives and process for preparing the same. 1994. Korea Res. Inst. Chem. Technology EP 622 367. 

Pyridyl quinolone carboxylic acids, (V), and 7-piperazine quinazolin-2,4-dione derivatives, (VI), prepared by Park (5) and Domagala (6), respectively, exhibited broad-spectrum antibacterial activity with reduced cytotoxicity. 

Quinolone and fluoroquinolone antibiotics are a group of highly-potent, synthetic antibiotics, derived from 3-quinolone carboxylic acid They are used as broad-spectrum antibiotics in the treatment of both human and veterinary diseases. 

Cholinergic receptor agonists Muscarinic receptors Benzyl quinolone carboxylic acid analogs Cevimeline EUK1001 Lanomeline Vedaclidine Nicotinic receptors Nicotinic analog ZY-1... 

Mistry SN, Valant C, Sexton PM, Capuano B, Christopoulos A, Scammells PJ (2013) Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the Ml muscarinic receptor. J Med Chem 56 5151-5172... 

A related strategy was suggested in which one of the reactants is attached via a linker to tetrabenzo[a,c,g,i]fluorene (Tbf). The reaction product can now be purified by taking advantage of the high affinity of Tbf to charcoal in polar solvents (mixture of DCM and methanol). Desorption can be affected with non polar solvents such as toluene [144]. The method was exemplified by the synthesis of a quinolone carboxylic acid derivative (ciprofloxacin). 

Notarianni, L.J. Jones, R.W. Method for the determination of ofloxacin, a quinolone carboxylic acid antimicrobial, by high-performance liquid chromatography. J.Chromatogr., 1988, 431, 461-464... 

Modifications of the Gould-Jacobs reaction have led to many versatile quinolone syntheses. In Table V, entry 4, ring closure of the tertiary en-aminone fails in a high-boiling solvent, but gives the quinolone carboxylic acid with a catalytic amount of phosphorus pentoxide or polyphosphoric acid in refluxing nitrobenzene. This modification is now generally applied to the preparation of quinolones from tertiary enaminones such as the fused quinolone, entry 5 (an important intermediate for fluoroquinolone antibacterials). 

Quinolone - quinolone carboxylic acid (C12H11NO3) Quinolone - temafloxacin (C21H18F3N3O3)... 

For examples of quinolone antibiotics we can choose ofloxacin, whose synthesis was discussed in detail in Chapter 22, and rosoxacin, whose synthesis is discussed below. Both molecules contain the same quinolone carboxylic acid framework, outlined in black, with another heterocyclic system at position 7 and various other substituents here and there. 

We have examined the application of this media for improving purification efficiency of quinolone carboxylic acids and short peptides which were prepared in rapid microwave assisted synthesis. 

Naoki O, Toshifumi A (2003) Process for producing antibacteriril quinolone-carboxylic acid... 

Ganapati Reddy P, Baskaran S (2001) Microwave assisted amination of quinolone carboxylic acids an expeditious synthesis of fluoroquinolone antibacterials. Tetrahedron Lett 42 6775-6777... 

Yang F, Shipe W, Bunda J, Nolt M, Wisnoski D, Zhao Z, Barrow J, Ray W, Ma L, Wittmann M, Seager M, Koeplinger K, Hartman G, Lindsley C (2010) Parallel synthesis of M-biaryl quinolone carboxylic acids as selective Mi positive allosteric modulators. Biooig Med Chem... 

Trkovnik M, Ivezic Z (2000) Synthesis of some new coumarin-quinolone carboxylic acids. J Heterocycl Chem 37 137-141... 

For the synthesis of new-generation antibacterial quinolone carboxylic acids, reduction of a2aspiroketones by Phaeocrepsis sp. JCM 1880 afforded the corresponding (R)-alcohols in high ee as shown in Figure 11.10c [60,61]. 

Synthesis of an Intermediate for a New-Generation Antibacterial Quinolone For the synthesis of new-generation antibacterial quinolone carboxylic acids. 

A surprising development involving the 3-position has been presented (61,62). This position traditionally has had a carboxylic acid group and attempts to replace the carboxylate have resulted in lower antibacterial activity. However, it was demonstrated that the carboxylate could be replaced with an isothiazolo ring fused between the 2- and 3-position of the quinolone nucleus. A-62824 [111279-87-9] (22), illustrates this stmctural modification as apphed to ciprofloxacin. 

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