Synthesis of N -Alkyl Enamino Ketones Based on 3-Acyl-4 H -polyfluorochromen-4-ones and Their Antimicrobial Activity
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hesis of N-Alkyl Enamino Ketones Based on 3-Acyl-4Hpolyfluorochromen-4-ones and Their Antimicrobial Activity K. V. Shcherbakova,*, M. A. Artemyevaa, Ya. V. Burgarta,b, N. A. Gerasimovac, N. P. Evstigneevac, and V. I. Saloutina,b a
Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, Yekaterinburg, 620990 Russia b c
Yeltsin Ural Federal University, Yekaterinburg, 620002 Russia
Ural Research Institute of Dermatovenerology and Immunopathology, Yekaterinburg, 620076 Russia *e-mail: [email protected]; [email protected] Received June 5, 2020; revised June 15, 2020; accepted June 26, 2020
Abstract—New N-substituted enamino ketones were synthesized by directed transformation of 3-acetyl- and 3-benzoyl-5,6,7,8-tetrafluoro-4H-chromen-4-ones by the action of highly basic primary amines as a result of opening of the pyranone ring and deacylation. The synthesized N-hexyl and N-octyl derivatives were evaluated for fungistatic and bacteriostatic activities. Keywords: enamino ketones, 3-acylpolyfluorochromen-4-ones, primary aliphatic amines, pyranone ring opening, deacylation, antimicrobial activity
DOI: 10.1134/S1070428020090171 Enamino ketones are versatile synthons widely used in organic synthesis; their potential stems from the combination of highly reactive electrophilic and nucleophilic sites [1–4]. In addition, enamino ketones are promising scaffolds for the design of new medicines [5–8], since various biologically active compounds have been found among their derivatives. For example, N-(adamantan-1-yl) enamino ketones were reported to exhibit high anti-inflammatory and cytotoxic activities [9]. N-(Hydroxyalkyl)-β-enaminone derivatives of curcumine showed cytotoxic affect in combination with good bioavailability, which makes them promising candidates for the preparation of antitumor agents [10, 11]. Among the enamino ketone series, the most interesting are their cyclic derivatives, N-aryl-3-aminocyclohex-2-en-1-ones, which showed analgesic and anti-inflammatory activity [12–14] at a level comparable to celecoxib [15], antihistaminic and antiepileptic effects [16–21], and cytotoxicity comparable to that of doxorubicin [22]. Furthermore, enamino ketone moiety is a structural fragment of many heterocyclic systems. Substituted pyridobenzimidazoles are GABA A and GABA B receptor modulators and are interesting as new anxiolytics [23–26]. Oxoquinoline-3-carboxylic acid derivatives showed a broad spectrum of antimicrobial activity and are now used as modern drugs;
examples are ciprofloxacin, levofloxacin, delafloxacin, etc. [27–30]. Growing interest in organofluorine compounds should be noted since the presence of electron-withdrawing fluorine atoms in organic molecules gives rise to not only new synthetic possibilities but also various biological activities [31, 32]. N-Aryl-substituted enamino ketones can be obtained by means of transformation of flavones and chromones by the action of amines [33, 34]. We previously showed that 3-acylpolyfluorochromen-4-ones 1 and 2 react with strong
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