2-Quinolone synthesis from quinoline

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-... 

A method was developed for the synthesis of quinoline derivatives from isatoic anhydrides and lactones. The amino ketones formed at the first stage were then converted into the desired products by cyclocondensation after isolation or by direct heating of the reaction mass. Thus, the reaction of the anhydride 2 with the butyrolactones 94 in the presence of lithium diisopropylamide gave the amino ketones (95) (yield 99%), which when boiled in toluene gave 4-hydroxy-3-R-l-methyl-2-quinolones 96 (yield 98% with R = H or 70% with R = Me). It was established that the latter exist in two isomeric forms 96a,b [57],... 

The group of Nakagawa reported the synthesis of quinoline 71 from N-allyl o-aminostyrenes 69 by using an RCM approach. Attempted deprotection of the dihydroquinolines 70 resulted in quinolone 71 (Scheme 20). Only one example was described, in quantitative yield (01TL8029). 

In 1994, a procedure for the synthesis of benzo[c]-2,7-naphthyridines from pyridine methylstannanes and ort/jo-bromoacetanilides was reported based on a palladium catalyst. " By using CuO as a promoter, good yields of the products were formed (Scheme 3.26a). In 2004, Banwell s group reported the synthesis of quinolines, 2-quinolones, phenanthridines, and 6(5H)-phe-nanthridinones via palladium-mediated Ullmann cross-coupling of... 

Sharma K, Fernandes P (2006) Synthesis and biological activity of substituted quinolones derived from 6-fluoro-3-carbethoxy-lH-quinolin-4-one. Ind J Heterocycl Chem 15 253-258... 

The enamine will normally prefer to adopt the first configuration shown in which cyclization is not possible, and (perhaps for this reason or perhaps because it is difficult to predict which quinoline will be formed from an unsymmetrical 1,3-dicarbonyl compound) this has not proved a very important quinoline synthesis. We shall describe two more important variants on the same theme, one for quinolines and one for quinolones. 

Syntheses of the antibiotic compounds deoxynybomycin (100) and nybomycin (102) as well as related heterocyclic compounds have been described (Scheme 7). The 8-hydroxy-2-quinolone (97), readily prepared from o-anisidine in three steps, was converted into the fused oxazoline-quinoline derivative (98) by successive nitration, reaction with dibromomethane, and hydrogenation. Adaptation of the Doebner-von Miller quinoline synthesis to (98) provided the tetracyclic product (99), which upon methylation and oxidation gave deoxynybomycin (100) in 0.83% overall yield from o-anisidine. The key intermediate... 

As shown in Scheme 1.46, a simple synthesis of complex fused 1,4-benzoxaz-epin-2-one derivatives 86 and 87 was aehieved via a three-component leaction of quinoline or isoquinoline, acetylene dicaiboxylic esters and l-(6-hydioxy-2-isopio-penyl-l-benzofman-yl)-l-ethanone in water, in the absence of aiy catalyst [68]. Presumably, this transformation proceeds via the initial formation of a 1 1 zwitter-ionic intermediate 88 from the Michael addition of isoquinohne (or quinolone) to the activated ester. A proton transfer reaction takes then place in which this species is protonatedby the phenol group in the l-(6-hydroxy-2-isopropenyl-l-benzofuran-yl)-l-ethanone substrate, and this is followed by a second Michael addition of the resulting phenoxide anion to the isoquinohnium ion to afford intermediate 88, containing benzofuryl and isoquinoline ring systems. This intermediate then undergoes... 

Further studies with P. citrinum VKM FW-800 obtained from the permafrost region of Northern Russia, led to the isolation of the alkaloids (+)-quinocitrinine A and (—)-quinocitrinine B, which are diastereomers at the C-1 and C-9 stereocenters (186). These alkaloids were the first pyrrolo[3,4-lr]quinoline-type representatives isolated from microbial sources. Their structures are unique in that a quinolone skeleton is conjugated with a y-lactam ring. A biomimetic total S3mthesis of quinolactacin B was reported by Tatsuta s group (215). A new enantioselective synthesis of quinolactacins A2 and B, via the skeletal rearrangement of a p-carboline to the pyrrolo[3,4- ]quinolin-4(lf-D-one system by an... 

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