Quinolones confirmation

The structure of the product of the Reimer-Tiemann reaction of 1,2,3-trimethylindole (24) has been confirmed as 3-dichloromethyl-1,3-dimethyl-2-methyleneindoline (25) by spectroscopy and oxidation to the iV -methyloxindole when the dichlorocarbene was generated under neutral conditions a ring-expanded product, 3-chloro-1,4-dimethyl-2-methylene-1,2-dihydroquinoline (26) could be isolated and oxidized to the corresponding a-quinolone. These reactions presumably proceed by mechanisms similar to those discussed for 2,3-di-... 

The structure of l-methyl-2-quinolone (57), from the aposematic beetle in the genus Metriorrhynchus (Table V), was expected from the mass spectral data and was confirmed by comparison with an authentic sample (97). 

Phenylpropanamide (130), from the aposematic beetle (genus Metrior-rhynchus) (Table VIII), has been purified by gas chromatography from the methanol extract. Its structure is presumed from mass spectral data and was confirmed by comparison with a synthetic sample (97). The co-occurrence of amide 130 and l-methyl-2-quinolone (57) in this beetle suggests a common pathway of biosynthesis and that they may be derived from the amino acid phenylalanine. 

Confirmation of the identity of the suspected liquid chromatographic peaks in quinolone analysis can be made by converting the analytes to the corresponding decarboxylated derivatives and analyzing them by gas chromatography-mass spectrometry (195, 196). Most promising screening and even confirmatory methods in terms of simplicity, selectivity, and sensitivity, are those described by Munns et al. (196), Roybal et al. (188), and Eng et al. (193). 

The permeability values of CNV97100, a fluoroquinolone derivative, were obtained in different segments of rat small intestine. The compound was in solution and the pH of the perfusion fluids in each segment were the same. The permeability was lower in the terminal segment of the small intestine in accordance with the higher expression level of P-gp. In order to confirm that a saturable carrier was present, experiments at different concentrations of the quinolone were performed in the ileum and also in the whole small intestine. In both cases a non-linear correlation between permeability and concentration was found where, at the higher concentrations, the permeability values were higher thanks to saturation of the secretion transporter. 

Density functional theory calculations (Becke3LYP/6-31G ) were employed to elucidate the geometry of the complex between chiral host ent-44 and 2-quinolone (45) as a representative and simple guest molecule [65]. The optimized geometry depicted in Fig. 1 confirms the assumed almost parallel alignment of the tetrahydronaphthalene shield and the guest molecule. The bond lengths for the two NH --0 bonds were calculated to 1.87 and 1.80 A. 

Allyloxy-2,3-dimethylquinoline on heating without a solvent at 200° for only 30 minutes afforded in yields as high as 92% a product with a quinolone structure. Confirmation of this formulation came from the following series of transformations (1) treatment with phosphorus oxychloride which gave the 4-chloro compound and... 

Antibiotics. Long-term administration of antibiotics could lead to vitamin B6 deficiency, If symptoms of peripheral neuropathy develop (numbness and tingling of the extremities), administer vitamin B6. Sulfasalazine can decrease the absorption of folic acid, and trimethoprim can cause folate deficiency, hence the need to administer folic acid if there is evidence of deficiency. Rifampicin can cause disturbances in vitamin D metabolism and lead to osteomalacia. The absorption of tetracyclines can be reduced by calcium, magnesium, iron and zinc, while this antibiotic could also decrease the absorption of these minerals. This effect is probably least with minocycline and is not confirmed with doxycycline. Doses of minerals and antibiotic should be separated by at least 2 hours. The absorption of quinolones is reduced by cationic and anionic supplements. 

The neurotoxic potential differs considerably among the various beta-lactam antibiotics, and experimental models have been developed for investigating this (51,52). Currently, imipenem + cilastatin appears to cause the highest frequency of neurotoxic effects (53,54) and the above-mentioned risk factors have been particularly confirmed with this compound (SEDA-18, 261) (55). Quinolone antibiotics, which themselves are proconvul-sant, can potentiate excitation of the central nervous system by beta-lactam antibiotics, at least in animals (56,57). 

The structure of maculosidine as 6,8-dimethoxydictamnine has been confirmed. Hydrogenolysis, followed by acid hydrolysis, gave 6,8-dimethoxy-3-ethyl-4-hydroxy-2-quinolone, identical with a synthetic specimen (104). The alkaloid has been synthesized (105) by the method of Tuppy and Bohm. Maculine (6,7-methylenedioxydictamnine) has been synthesized by Ohta and Mori (106, 107) by a modification of Grundon s method (108). 3,4-Methylenedioxyaniline was condensed with ethyl 2-benzyloxyethylmalonate and the resulting 4-hydroxy-2-quinol-... 

Under controlled photolytic conditions, the rearranged oxidized product 273 was isolated from acetonitrile solution, and its structure was confirmed by X-ray analysis (Figure 19). Extensive photolysis led eventually to formation of di- and trimethyloxindoles, 13 and 14, a quinolone derivative, 265, and, in the case of spirooxazines, naphthoxazole 268. In the case of the two spiropyrans included in the study, 2-hydroxyl-l-naphthaldehyde and 5-nitrovanillin were also formed. It is... 

Flindersine and a new quinolone alkaloid, 3-dimethylallyl-4-dimethyl-allyloxy-2-quinolone, C19H23O2N (mp 114°-115°) were isolated. Mass and NMR spectroscopy indicated structure LXVIIa for this base. Minor chemical reactions served to confirm this structure, particularly catalytic hydrogenation, which induced rapid hydrogenolysis of the ether linkage 102). 

Another 4-methoxy-l-methyl-2-quinolone (10) was isolated from the roots of Spathelia sorbifolia L. (25). The constitution of the alkaloid was established by spectroscopy and confirmed by dimethylation of quinolone 9 with dimethyl sulfate in dimethylformamide. 

The presence of a phenolic group was indicated by a positive ferric chloride test and by methylation to ether 31, which showed reactions typical of quaternary salts of the O-methylbalfourodinium type. Thus, heating O-methylribalinium iodide in pyridine furnished the 4-quinolone (32), which was reconverted into the quaternary salt by methyl iodide. The structures of 30 and 32 were confirmed by NMR and mass spectrometry. 

Yunusov and his collaborators (87) obtained the alkaloid haplamine from Haplophyllum perforatum. Spectroscopic data indicated that haplamine was a methoxyflindersine, and it was assigned structure 143 on the basis of its reaction with base, followed by methylation, to give 4,6-dimethoxy-l-methyI-2-quinolone, although evidence for the structure of this degradation product was not recorded. The constitution of the alkaloid has since been confirmed by synthesis (see Section III,G,2). 

The structure of bucharaine has now been confirmed by synthesis (Scheme 25). The geranyl ether 286 was prepared from 4-hydroxy-2-quinolone and geranyl chloride. Selective epoxidation with m-chloro-perbenzoic acid yielded monoepoxide 287. Reaction of the epoxide with formic acid gave the formate ester 288, which on treatment with base was converted into bucharaine (206). 

A second alkaloid from V. ampody was shown to be the primary alcohol 301 (134). The NMR spectrum showed a resonance at .35 (2H, triplet, -C//2OH), appearing at lower field after acetylation. The third alkaloid was the 4-quinolone 302 with a Cu side chain. The presence of a ketonic function was indicated by IR absorption at 1705 cm-1, and the structure was confirmed by NMR and mass spectrometry. 

Piozzi et al. (219) have confirmed 317 as the structure of japonine by synthesis (Scheme 27). Application of Darzen s reaction to 2-nitro-5-methoxybenzaldehyde furnished epoxide 314. This was converted with hydrogen chloride and hydroquinone into 315, which was reduced to the 3-hydroxy-4-quinolone 316 methylation then afforded japonine as the major product. 

Confirmation of the isoprenoid nature of the furan rings of dictamnine (328) and of N-methylplatydesminium salt (326) in S. japonica was provided indirectly by Grundon and his co-workers (224), who showed that the 3-prenylquinolones 321 and 322 labeled at - with 14C were good precursors of both alkaloids (3.6-4.8% incorporation). Specific incorporation of the precursors into dictamnine was indicated by oxidative degradation by a method similar to that used previously. N-Methylplatydesminium salt was counted as its base-cleavage product edulinine (256), which was converted into isodictamnine (Section IV,B,3) oxidation via 3-carboxy-4-hydroxy-l-methyl-2-quinolone gave 14C-labeIed carbon dioxide. 

The only note dealing with quinoline derivatives of fungal origin is by way of confirming the well-known fact that viridicatin (3-hydroxy-4-phenyl-2-quinolone) is produced by Penicillium cyclopium ... 

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