N-Methyl-2-quinolone

The occurrence of new furoquinoline alkaloids and their physical properties are indicated in Table VII. N-Methyl-4-quinolones, the so-called isoalkaloids are well known one example is isodictamnine (164), obtained by heating dictamnine with methyl iodide. Isodictamnine, iso-pteleine, isomaculosidine, and isoflindersiamine have now been recognized as constituents of rutaceous species the N-isopentyl alkaloids of Acronychia are also in this category. The alkaloids discussed in this section are grouped in accord with the pattern of oxygenation in the aromatic ring. 

The reaction of haplophyllidine (11) or its hydration product, perforine (12), with concentrated sulphuric acid results in dehydration, loss of methanol, and cyclization the structure (13) of the product was established by spectroscopy and by conversion, with methyl iodide, into the corresponding N-methyl-4-quinolone. The reaction of the Haplophyllum alkaloid haplatine (14) with methyl iodide also results in formation of an N-methyl-quinolone ( 15), and in this case the methylation of the allylic hydroxy-group gives a second product (16). Reductive cleavage of haplatine furnishes the 3-ethyl-2-quinolones (17) and (18). ... 

Ptelea trifoliata is the only known source of hemiterpenoid quinoline alkaloids containing terminal double bonds, and nine compounds of this type have been isolated cf. Vols. 1—3, 5, and 7) the synthesis of two members of the group, O-methylptelefolonium iodide (26) and ptelefolone (29), has now been reported (Scheme 4). The 3-prenyl-4-methoxy-2-quinolone (24) was prepared by standard procedures and was converted with a peroxy-acid into a mixture of the dihydropyrano-quinolone (25) and the dihydrofuro-quinolone (27), Treatment of the latter with thionyl chloride and pyridine resulted in regiospecific elimination to give a terminal olefin, which afforded O-methylptelefolonium iodide (26). Successive reaction of the N-methyl-4-quinolone (28) cf. Vol. 7) with triphenyl phosphite dichloride and with pyridine resulted in an efficient synthesis of ptelefolone (29). 

N-Methyl-4-hydroxy-2-quinolone 183 in a three-component reaction gives spiro pyrano[3,2-c]qionoline-2-ones (02MI2), but indolones 213 with 4-hydroxy-6-methyl-2-pyridone 177 react in a complicated way (97BCJ1625). Ethoxycarbonyl-methylene indolone (Z = COOEt) forms pyrans 224, while dicyano analogs (Z = CN) yield substituted quinoline 225 (Scheme 85). 

A mixture of 114.0 g (0.587 m) of N-methyl-4-nitroacetanilide and 800 ml of ethanol was shaken with hydrogen over one teaspoon of Raney active nickel catalyst in water. A pressure drop of 127 psi was recorded (calc. 118 psi). The catalyst was removed by filtration and the ethanol filtrate refluxed overnight with 127.0 g (0.587 m) of the 9-chloro-7-methylimidazo[4,5-f]quinolone. The mixture was chilled, filtered, washed with ether and air-dried to give 75.5 g of 9-[p-(N-methylacetamido)anilino]-7-methyl-l-H-imidazo[4,5-f] quinoline... 

Alkylation of a series of 4-quinolones under basic two-phase conditions yields a mixture of the O- and A-alkylated derivatives [65], The ratio of the two isomers depends on the substituents. A-Alkylation is predominant (N 0 ratio = ca. >4 1) for most compounds but, somewhat surprisingly, the presence of a methyl group at either the 2- or 8-position results in a higher, or sometimes exclusive, yield of the N-alkylated product, irrespective of other substituents on the system. 

Glide docking of N-methyl-2-alkenyl-4-quinolones with MurE ligase... 

Guzman JD, Wube A, Evangelopoulos D et al (2011) Interaction of N-methyl-2-alkenyl-4-quinolones with ATP-dependent MurE ligase of Mycobacterium tuberculosis antibacterial activity, molecular docking and inhibition kinetics. J Antimicrob Chemother 66 1766-1772... 

The six optically active alkaloids ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, and the N-methylated N-methylephedrine and N-methylpseudoephedrine are described in detail in Reti s review (2). Two new alkaloids of related structure have since been identified in Ephedra species, namely, (9-benzoylpseudoephedrine (271) and the oxazolidine derivative ephe-droxane (272). The 4-quinolone derivative ephedralone, recently isolated from Ephedra alata (273), may be of similar biogenetic origin as the ephedrines. Ephedra species also contain macrocyclic alkaloids of more complex structure (275). The two major Ephedra alkaloids (—)-ephedrine and (+)-pseudoephedrine are diastereomers. (—)-Ephedrine has the erythro and (+)-pseudoephedrine has the threo configuration. 

Non-hemiterpenoid Quinolines.—New sources of the simple quinolines 4-methoxy-l-methyl-2-quinolone and its 8-methoxy-derivative (folimine) have been reported the former was isolated from Myrtopsis sellingii9 and from Zanthoxylum cuspidatum,16 and folimine was shown to be a constituent of Haplophyllum perforatum.5 The latter species also contains foliosidine (9), previously isolated from H. foliosum. The micro-organism Pseudomonas aertiginosa has been shown to contain 2-(hept-l-enyl)-4-quinolone (12).10 The structure of the alkaloid was established by n.m.r. and mass spectroscopy and by its synthesis from aniline and the j3-keto-ester Me(CH2)4CH=CHC0CH2C02Me. 

Hydroxy-l-methyl-3-prenyl-2-quinolones, cf. (22), are key intermediates in the synthesis of quinoline alkaloids, and usually are prepared in one stage from an N-methyl-aniline and diethyl prenylmalonate. Interesting new methods beginning with N-methylisatoic anhydrides, cf. (20), have been explored and briefly repor-... 

Very few synthetic compounds other tha,n the sulfa drugs have shown useful activity against systemic bacterial infections, particularly those due to Gram-negative bacteria. Activity of this kind was discovered in a series of l-alkyl-4-quinolones (60BRP830832), but the most active of these, l,2-dimethyl-6-nitro-4-quinolone and l-methyl-6-nitro-4-quin-olone-3-carboxylic acid, produced eye damage (opacity of the lens) that precluded clinical trial. A closely related 1,8-naphthyridine derivative, nalidixic acid (255), was later found to be effective, and it is largely used for urinary tract infections. The quinolone oxolinic acid (256) is also used for this purpose. These compounds inhibit enzymes concerned in DNA synthesis. 

Several further species of Flindersia have been examined for alkaloids and other extractives and the chemistry of this genus has been reviewed (118). The only new alkaloid found was iflflaiamine ([a] n — 0.6° hydrate, mp 62°-63° picrate, mp 207°-209°), the sole alkaloid of the wood of Flindersia ifflaiana F. Muell. (119), which is a dihydrofuroquinoline (XX). Its structure was largely elucidated by spectroscopic measurements. Its UV- and IR-spectra showed it to be a 2-alkoxy-4-quinolone, and the NMR-spectrum showed the presence of three C-methyl groups and one A-methyl (attached to aromatic ring N), a 1,2-disubstituted benzene ring, and other evidence supporting the 2-alkoxy-4-quinolone structure. 

N.27) 2(177)-quinolinone, 4-methyl-, 4-methyl-2-quinolone, 4-methyl-1 (H) -qulnolin-2-one [607-66-9] tautomeric form 2-quinolinol, 4-methyl-, 4-methylquinolin-2-ol, 2-hydroxy-4-methylquinoline [84909-43-3]... 

Echinopsine, l-Methyl-4(lH).quinolinone 1-metkyl-4Echinops ritro L. and other spp of Echinops, Campositae Greshoft, Rec. Trav. Chim. 19, 360 (1900) Ban kovskii et al, Hold. Akad. Nauk SSSR 148, 1073 (1963). Structure Spath, Kolbe, Monotsh. 43, 469 (1923). Synthesis Kondo, Ikawa, /. 

Hydroxy-2-quinolone is a biosynthetic precursor of quinoline alkaloids (see Section VII), and it is not surprising that compounds of this type occur in rutaceous plants (Volume IX, p. 225). Additional 4-methoxy-2-quinolones with or without N-methyl groups have now been reported. 

When heated briefly above its melting point, (+)-N-methyl-platydesminium iodide gave the 4-quinolone 52, [a]D + 82° (MeOH) (37), identified by comparison with the synthetic racemate (27). Higa and Scheuer (43) have now isolated from Pelea barbigera (Gray) Hillebrand quinolone 52, named isoplatydesmine. Araliopsis soyauxii has been shown to contain (+)-isoplatydesmine as the major alkaloid of the root bark (44) the same enantiomer is a constituent of A. tabouensis (45). 

Bucharaine (C19H25NO4 mp 151-152°) gave a mono-O-acetate, an N-methyl derivative, and a dibromide, and with platinum and hydrogen it furnished 4-hydroxy-2-quinolone and an oil, C10H22O2. On this basis bucharaine was assigned partial structure 279, which was also in accord with the IR and UV spectra the alkaloid was believed to contain a double bond and a secondary and a tertiary hydroxyl function (201). The alkaloid... 

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 water insoluble bases, together with those recovered from the mother liquors of the l-methyl-2-quinolone hydrochloride, are heated with 40 cc. of fuming hydrochloric add in a sealed tube at 175 for 2.5 hours, whweby the 4-methoxy-2-n-amyl-... 

Quaternary papaverinium salts (22) have been converted into enamines (23), which have been oxidised by singlet oxygen or by oxygen and cuprous chloride with fission to the quinolones (24). N-methyl-3,4-dihydropapaverinium salts... 

Yoshikazu A, Ichiro A, Kazuhiko 1, linuma F, Hosaka N, Ishizaki T (2005) Synthesis and antibacterial activity of the 4-quinolone-3-carboxyhc acid derivatives having a trifluoro-methyl group as a novel N-1 substituent. J Med Chem 48 3443-3446... 

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