Herein we reported a transition metal free strategy for the synthesis of 4 quinolones, benzopyran derivatives and other fused systems by the domino reaction of 3benzoylchromones, containing a leaving group in the position2 of the benzoyl moiety. Quinolones oxoquinolines are a versatile subgroup within the quinoline family with. For many gramnegative bacteria, dna gyrase is the target, whereas topoisomerase iv is the target for many grampositive bacteria. Get a printable copy pdf file of the complete article 1. Position 1 is nitrogen in the bicyclical aromatic ring structure, with an alkyl group ethyl or perhaps cyclopropyl often attached there. Mediated cyclization with cleavage of aromatic co bond. More than quinolones and analogs have since been synthesized and evaluated in an attempt. Figure 1 are a series of synthetic antibacterial agents derived from, or related to, nalidixic acid and oxolinic acid. Synthesis of halogenated 4 quinolones and evaluation of their antiplasmodial activity. Quinolones and fluoroquinolones have many things in common, but also a. The 6fluoroquinolones also known as 4 quinolones or quinolones. Synthesis of nheterocycles benzofused nheterocycles synthesis of 4 quinolones. Synthesis of halogenated 4quinolones and evaluation of. In addition, another class of antibiotic, called fluoroquinolones, were derived from quinolones by modifying their structure with fluorine.
Links to pubmed are also available for selected references. Currently, most research focus on the structure of quinolone metal complexes, however, the research on the. The key step involved a sp 2 sp 3 suzukimiyaura reaction between a common boronic ester lateral chain and various functionalised quinolone cores. Piperazinyl quinolones such as ciprofloxacin, ofloxacin and levofloxacin are an important group of quinolone antimicrobials which are widely used in the treatment of various infectious diseases. Synthesis of the antimalarial chloroquine 9 via the gould jacobs route for generation. Quinolones exert their bacteriocidal effect by interfering with a bacteriums ability to make dna replication. We here report a conditioncontrolled divergent synthesis strategy of chalcones, quinolones and indoles, which was achieved via a ch activation reaction of nnitrosoanilines and cyclopropenones. Resistance to quinolones occurs through chromosomal mutations in the genes encoding these enzymes and by porin and efflux mutations. Variations of ag salts are observed to be crucial for divergently constructing the three distinct chemical scaffolds. Department of basic medicinal sciences, graduate school of pharmaceutical sciences, nagoya university, chikusa, nagoya 464.
Since quinolones, like pyridones, can be converted into chlorocompounds with pocl 3, they can be used in nucleophilic substitution reactions to build up more complex quinolines. Synthesis of aring quinolones, ninemembered oxolactams. Full text full text is available as a scanned copy of the original print version. Quinolone and fluoroquinolone medicinal products for systemic and inhalation. A coiiicatalyzed enaminonedirected ch coupling with dioxazolones and subsequent deacylation of an installed amide group provides quinolones, an important heterocyclic scaffold for diverse pharmaceutically active structures. The synthesis of four quinolone natural products from the. A quinolone antibiotic is a member of a large group of broadspectrum bacteriocidals that share. The quinolone class of drugs were discovered in the 1960s when lesher et al. Quinolones mechanism of action quinolones are bactericidal. Most imaginable reaction types have been successfully applied and used, as many of the synthetized compounds exhibit interesting biological activity in various fields. It and 2 quinolone are the two most important parent meaning simplified quinolones. Synthesis and structureactivity relationships of a series of amino acid prodrugs of racemic and chiral 73aminolpyrrolidinyl quinolones.
But how do quinolones destroy these microbes without hurting our cells. Synthesis and evaluation of 4hydroxy quinolinone derivatives as antioxidants of lubricating grease modather f. Divergent synthesis of quinolone natural products from. This project demonstrates the synthesis of fluoro quinolones in general with a new and efficient method that employs halogenated ethyl diazoacetates in reaction with indolederivatives. Antibiotics kill or inhibit the growth of bacteria. Eladly3 1faculty of science, alazhar university, assiut, egypt 2faculty of education, ain shams university, cairo, eg ypt 3egyptian petroleum research institute, cairo, egypt abstract. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry nearly all quinolone antibiotics in use are fluoroquinolones, which contain a fluorine atom in their. Tandem synthesis of pyrrolo2,3bquinolones via cadogen. Basic structure of these compounds figure 6 is a bicy clic structure, which contains a ring of type.
Each agent inhibits bacterial dna synthesis by forming a ternary. They inhibit bacterial dna synthesis in several ways causing rapid cell death quinolones bind the dnadna gyrase topoisomerase ii complex blocking further dna replication quinolones mechanism of action quinolones block topoisomerase iv. These substances inhibit synthesis of bacterial dna via binding to. Quinolones can enter cells easily via porins and, therefore, are often used to treat intracellular pathogens such as legionella pneumophila and mycoplasma pneumoniae. Pdf one of the most promising and vigorously pursued areas of contemporary antiinfective chemotherapy is that of antibacterial quinolones. Two divergent synthetic routes are reported offering access to four quinolone natural products from pseudonocardia sp. Get a printable copy pdf file of the complete article 11m, or click on a page image below to browse page by page.
Quinolones rapidly inhibit dna synthesis by promoting cleavage of bacterial dna in the dnaenzyme complexes of dna gyrase and type iv topoisomerase, resulting in rapid bacterial death. Synthesis of fluoroquinolone derivatives having saturated alkyl. A quinolone antibiotic is a member of a large group of broadspectrum bacteriocidals that share a bicyclic core structure related to the substance 4 quinolone. In the present study, we synthesized a new series of levofloxacin derivatives and evaluated their antibacterial activities. Highly soluble quinolone prodrugs with in vivo pseudomonas activity. This is a pdf file of an unedited manuscript that has. Some compounds in this class have been shown to inhibit the synthesis of. Inhibition of nucleic acid synthesis by antibiotics biofiles 2006, 1. Quinolones are potent antimicrobial agents with a basic chemical structure. Exploration of new sustainable synthetic methods for the. The key reaction in the new method is the synthesis of the quinoline precursor.
View the article pdf and any associated supplements and figures for a period of 48 hours. Key steps to the natural products involved a regioselective epoxidation, an intramolecular buchwaldhartwig amination and a final acid. Synthesis and antibacterial activity of novel levofloxacin. Exploration of new sustainable synthetic methods for the synthesis of fused pyridines and 4 quinolones based on the domino reaction of chromones and. An efficient onepot synthesis of 41h quinolones through an orthogonal engagement of diverse ohaloaryl ynones with ammonia in the presence of cui, involving tandem michael addition and arcsp2n coupling, is presented. Chemical structure and pharmacokinetics of novel quinolone agents. The substrate propiolates were prepared from the corresponding silylalkynes with carbon dioxide by kondos carboxylation method using n,n. It is a synthesis of a dihydroisoquinoline by what. The substrate scope of this convenient protocol, wherein ammonium carbonate acts as both an in situ ammonia source and a base toward diverse 2substituted 41h quinolones. The oxidation of indolofused 28oxoallobetulin or methyl platanoate with ozone led to a mixture of a quinolone as the major product and a nineme synthetic methodology in obc.
Inhibition of nucleic acid synthesis by antibiotics. Attempts to activate the carbonyl of the carboxyl group of 4chloro acid 2a by converting it to an acid halide were also unjustified. In this study, we report the synthesis of 4 quinolones in one step, under microwave irradiation and with diphenyl ether as a solvent, using ethyl acetoacetate and electron rich anilines. Antibiotics are chemotherapeutic agents used to inhibit or kill bacteria. The synthesis of four quinolone natural products from the actinomycete pseudonocardia sp. The first quinolone was isolated as a by product of. An efficient transitionmetalfree oxidative cyclization reaction of alkynes with isatins enables a facile synthesis of structurally diverse 4 quinolones. The synthesis of quinolone natural products from pseudonocardia sp.
Other aminopyrrolidines also are compatible for activity, the nature of the c7 substituent along with c8 also strongly affects the target preferences dna gyrase andor dna topoisomerase iv of quinolones. Synthesis of 4quinolones, benzopyran derivatives and. This paper describes an access to new nitrogencontaining heterocyclic triterpenoids by the reaction of 2,3indolotriterpenoids with ozone and dimethyldioxirane. Structureactivity relationships of the fluoroquinolones.
The synthesis, characterization and application of. Quinolones are a key group of antibiotics that interfere with dna synthesis by inhibiting topoisomerase, most frequently topoisomerase ii dna gyrase, an enzyme involved in dna replication. Quinolones rapidly inhibit dna synthesis by promoting cleavage of bacterial dna in the dnaenzyme complexes of dna gyrase and type iv topoisomerase, resulting in rapid bac. Quinolones inhibit two enzymes that are required for bacterial dna synthesis, i. Synthesis of polysubstituted 4 quinolones xiang wu, langlang zheng, liping zhao, chengfeng zhu and yougui li anhui province key laboratory of advanced catalytic materials and reaction engineering, school of chemistry and chemical engineering, hefei university of technology, hefei 230009, china. Design, synthesis, and evaluation of novel n1 fluoroquinolone. By senior scientist henrik hasman national food institutedtu antibiotics.
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