Dihydro-4-quinolones, synthesis

The synthesis and antibacterial properties of norfloxacin (2a) were described in 1980 [65]. In this key paper in the evolution of quinolone antibacterial agents, a series of 6,7,8-polysubstituted-l-ethyl-l,4-dihydro-4-oxoquinoline-3-carb-oxylic acids (13) was synthesized, employing previously developed quantitative structure-activity relationships (QSAR) for the corresponding 6-, 7- and 8-monosubstituted derivatives versus Escherichia coli. The QSAR analysis... 

Perhydro derivatives of pyrido[l,2-6][l,2]oxazines are frequently applied in the total synthesis of various alkaloids to control the stereochemistry, and 4-(substituted amino)-5-fluoro-7-oxo derivatives of 3,7-dihydro-2//-pyrido[3,2,l-f7][2,l]benzoxazine- and l,2,3,7-tetrahydropyrido[3,2,l-//]cin-noline-8-carboxylic acids are considered as a subfamily of the third generation of antibacterial quinolones. 

Norfloxacin Norfloxacin, l-ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)-3-quinolincarboxylic acid (33.2.18), is the first representative of a series of fluorinated qninolones as well as the first drug of the quinolone derivatives used in medicine that contains a piperazine snbstituent. The method of synthesis is basically the same as that suggested for synthesizing nalidixic and oxolinic acids. 

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, /. 

Enders and co-workers developed a highly enantioselective synthesis of 4-aryl-dihydro-2-quinolones by combining enaminone chemistry and asymmetric Michael additions with the SAMP/RAMP-hydrazone method. As shown in Scheme 125, the cyclic 1,3-diketones 457 are transformed into... 

Alcohols can be converted into halides if lithium halides (F, Cl, Br, I) or Mel are used in the presence of TPP/DEAD. Kim and Kim were interested in the preparation of (5)-(-)-7,8-difluoro-3,4-dihydro-3-methyl-2//-1,4-benzoaxine (223), a key intermediate for the synthesis of the commercially available quinolone antibiotic levofloxacin. Initial attempts to cyclize 222 under the standard Mitsunobu conditions employing the TTP/DEAD conditions failed to give acceptable yields even when the reaction was refluxed for 1 h in benzene or acetonitrile. Addition of several equivalents of zinc chloride gave the desired cyclized product, some chlorinated intermediate, and none of the DEAD adduct 224. The DEAD adduct was the major product under the standard Mitsunobu conditions. The stereochemistry of the obtained products, which indicates retention of stereochemistry, suggests that the reaction proceeded via a chloride intermediate. 

Edmont D, Marot C, Chenault J (2002) Synthesis of novel fused tricyclic quinolones 4a,5-dihydro-lH-[T,2,4]triazino[l,6-a]quinoline-2,4,6(3//)-triones. J Heterocycl Chem 39 1161-1167... 

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