Rings quinolone

Keywords 2-Pyridone 2-quinolone Ring-fused 2-pyridone... 

Reaction of these antibiotics with chlorine mostly generated chlorinated and OH-substituted by-products [86, 87]. Unlike fluroquinolones, whose quinolone ring is left mostly intact, disinfection with CIO2 may diminish the antibiotic capacity of tetracyclines because it leads to cleavage of the tetracyclines ring system [86,88]. On the other hand, oxidation of p-lactam antibiotics such as penicillin, amoxicillin, and cefadroxil with CIO2 leads to the formation of hydroquinone and a wide range of substituted phenols [89]. 

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. 

In the synthesis of these compounds, the 2-(l-chloro-2-fluoroethyl)thio compound 200 has been debenzylated and intramolecular cyclization was carried out to afford the 1,3-thiazetidine ring in compound 201 (Scheme 65). The alternative /3-elimination reaction is inhibited because the lone pair of electrons on the sulfur atom of the anion is delocalized on the quinolone ring and so cannot attack the cr-carbonatom of the chlorosulfenyl group <1999CPB1765>. 

Grohe K. The chemistry of the quinolones Methods of synthesizing the quinolone ring system. In Quinolone Antibacterials. Kuhlmann J, DalhoffA,... 

Quinolone ring closure to fused heterocycles is possible as shown in equation 33 for the formation of pyrazoloquinolones, which are potential pharmaceuticals51. A modification of this kind of ring closure is the replacement of the carboxyl group by a nitrile leading to aminoquinoline derivatives51 (equation 33). 

A novel quinolone-ring fused oxepine 56 (n = 1), reported by Joseph et al., was accessed by a ring-closing metathesis reaction on the precursor 55, which was made in turn from 53 via 54, and a Claisen rearrangement on the last compound. An aza analogue of 56 (n = 1) was made in a similar direct approach <03SL2089>. 

The chemical structure at position 8 in the quinolone ring probably determines the phototoxic potential, since the introduction of a methoxy group at this position markedly reduces the phototoxicity of individual drugs (65). 

The aza-annulation methods developed for conversion of 88 to 94 were extended to the synthesis of the antileukemic and antitumor natural product ( )-camptothecin (125, Scheme 11 ).47 Aza-annulation of 109 with 121 in the presence of NaBH4 resulted in heterocycle formation to give 122 without subsequent elimination of the malonate species. A dye sensitized photo-oxidation promoted the rearrangement of the indolo[a]quinolizinone ring to the indolizino[l,2-h]quinolone ring 123. Compound 123 was converted to 124, which constituted a formal total synthesis of camptothecin (125). 

Dechlorination followed hy further reactions on the quinolone ring, degradation of the pyrrolidine side-chain (Deionized water pH 4)... 

Fluorocinnoline derivatives have recently been reported and aza-analogs of norfloxacin prepared (Fig. 24). Comparison of the activity of both compounds has indicated that the introduction of an additional nitrogen atom at position 2 of the quinolone ring causes a considerable decrease in activity. Among the other... 

Scheme 8.95 Synthesis of 2-quinolones ring from 3,3-diarylacrylamides.

Functionalization of the cinchona structure with a thiourea at the C6 position of the quinolone ring was demonstrated shortly after development of the C9 derivatives [69]. The transformation of the C6 methoxy group into a thiourea bearing a 3,5-di(trifluoromethyl)phenyl group, without affecting the stereochemistry at C9, resulted in a highly effective organocatalyst for the asymmetric Henry reaction of nitromethane with aromatic aldehydes (Scheme 6.28). 

Total Synthesis of Meloscine Meloscine 189, a member of the Melodinus alkaloids group, is noted for containing a six-membered quinolone ring within a mono-terpenoid Aspidosperma carbon skeleton. 

The majority of quinolones in clinical use belong to the subset of fluoroquinolones, which have a fluoro group attached to the central ring system. Among fluoroquinolones, there are molecules with one or two chiral centers. The position of a chiral center in relation to the quinolone ring influences antibacterial activity and pharmacokinetic parameters of isomers [4],... 

Enantiomers of compounds, in which chiral center is distant from 4-quinolone ring, such as lomefloxacin, clinafloxacin, gatifloxacin, and tosufloxacin, do not show significant differences in antibacterial activity and pharmacokinetic properties [5-9],... 

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