Moxifloxacin synthesis

The synthesis of the moxifloxacin core (de Souza, 2006 Martel et al., 1997 Seidel et al., 2000) proceeds from a Grohe-Heitzer sequence as described earlier in the chapter. Unlike the traditional Grohe-Heitzer sequence, however, the opening step involved the reaction between acid chloride 101 with the mono potassium salt of malonic acid monoethyl ester (102) in the presence of triethylamine to deliver ketoester 103 (Scheme 4.18). Treatment of 103 with ethyl orthoformate furnished acrylate 104, which reacted with cyclopropyl amine to afford 105. Cyclization of 105 in the presence of sodium fluoride in DMF gave the moxifloxicin core 106. 

The first quinolone, nalidixic acid, was isolated as a byproduct of the synthesis of chloroquine. It has been available for the treatment of urinary tract infections for many years. The introduction of fluorinated 4-quinolones, such as ciprofloxacin (Cipro), moxifloxacin (Avelox), and gatifloxacin (Tequin) represents a particularly important therapeutic advance because these agents have broad antimicrobial activity and are effective after oral administration for the treatment of a wide variety of infectious diseases. Relatively few side effects appear to accompany the use of these fluoroquinolones, and microbial resistance to their action does not develop rapidly. Rare and potentially fatal side effects, however, have resulted in the withdrawal from the market of temafloxacin (immune hemolytic anemia), trovafloxacin... 

The first quinolone, nalidixic acid, was isolated as a byproduct of the synthesis of chloroquine. It has been available for the treatment of urinary tract infections for many years. The introduction of fluorinated 4-quinolones, such as ciprofloxacin (Cipro), moxifloxacin (Avelox), and gatifloxacin (Tequin), represents a particularly important... 

Moxifloxacin hydrochloride is a fluoroquinolone/anAbiotic. It interferes with microbial DNA synthesis. Moxifloxacin is indicated in the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chroific bronchitis, community-acquired pneumonia, uncomplicated skin and skin structure infections, and conjunctivitis caused by susceptible organisms. 

Synthesis of new hydroxybisphosphonate derivatives of ciprofloxacin 49 has been performed by using Cu-catalyzed 1,3-dipolar cycloaddition reaction between the corresponding azide and N-alkynyl substituted quinolone [169] (Scheme 22). Derivatives of gati- and moxifloxacin have been obtained similarly. All of these modified compounds maintained antibacterial activity of the starting quinolones and, in addition to that, exhibit osteotropic properties. 

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