Synthesis and Antimicrobial Evaluation of Dibenzo[b,e]oxepin-11(6H)-one O-Benzoyloxime Derivatives

Abstract

A series of dibenzo[b,e]ox(thi)epin-11(6H)-one O-benzoyloximes has been synthesized and structurally elucidated by means of IR, 1H-NMR, 13C-NMR, MS, and elemental analysis. The newly developed compounds were screened at concentrations of 200–25 μg/mL for their antibacterial activity against Gram+ve organisms such as Methicillin-Resistant Staphylococcus Aureus (MRSA), Gram−ve organisms such as Escherichia coli (E. coli), and at the same concentration range for their antifungal activity against fungal strain Aspergillus niger (A. niger) by the cup plate method. Ofloxacin and ketoconazole (10 μg/mL) were used as reference standards for antibacterial and antifungal activity, respectively. The dibenzo[b,e]oxepines 6a–c and 6e–h showed low antimicrobial activity (MIC 125–200 μg/mL) compared to the reference substances, whereas a major improvement (MIC 50–75 μg/mL) was achieved with the synthesis of the corresponding bromomethyl derivative 6d. Moreover, replacement of oxygen by its bioisosteric sulfur led to isomeric dibenzo[b,e]thi-epine derivatives 6g,h which significantly exhibited higher antimicrobial activity (MIC 25–50 μg/mL) against all tested culture strains used in the present study, demonstrating that a change of chemical class from dibenzo[b,e]oxepine to dibenzo[b,e]thiepine significantly improves the antimicrobial activity. Further variation, such as the oxidation of the thiepine sulfur to the corresponding isomeric dibenzo[b,e]thiepine 5,5-dioxide derivative 9, comparatively failed to exhibit high activity (MIC 200 μg/mL) against S. aureus, E. coli or A. niger.

A Parham cyclization approach to diaryl-fused seven-membered ring heterocyclic ketones

“…Current synthesis methods involve several reaction steps or restrictive reaction conditions such as strongly acidic media (intramolecular Friedel-Crafts) which preclude the incorporation of reactive functional groups. 5,8,9 Based primarily on work directed toward the preparation of symmetrical dibenzosuberones via intramolecular Parham cyclizations described by Reames et al 10 We have found that the Parham protocol is well-suited for the preparation of a variety of these classes of compounds. 11 This Letter describes a general protocol for a straightforward synthesis of diaryl-fused seven-membered heterocyclic ketones under Parham conditions.…”

“…The benzo-fused seven-membered heterocyclic ketones have been shown to possess central nervous system pharmacological activity while products derived from diaryl-fused 6,7,6 heterocyclic compounds have been shown to have utility in a variety of different therapeutic applications including treatment of cognitive disorders such as Alzheimer's disease and Huntington's disease through inhibition of histone deactylase, 1 the treatment of sleep disorders, [2][3][4] antimicrobial agents, 5 and agonists of the peroxisome proliferator-activated receptor 6 to name a few (Fig. 1).…”

Synthesis of two 2,3,4,5‐tetrahydrooxepin‐7‐ylamino)benzoate derivatives as antibacterial agents against Escherichia coli and Staphylococcus aureus

“…For several years now, the pharmaceutical and chemical industries have shown great interest in the development of new oxepine derivatives for therapeutic purposes. [1][2][3][4] In this sense, a report showed the preparation of benzoxepine-1,2,3-triazol via reaction of an azide analog with a terminal-alkyne derivative. [5] In addition, other data showed the synthesis of an oxazepine-dione analog from a semicarbazone.…”

A Novel Antioxidant Isobenzofuranone Derivative from Fungus Cephalosporium sp.AL031

“…Isobenzofuranone derivatives are an important class of compounds displaying a variety of biological effects, such as antioxidant, antimicrobial, antiplatelet, cytotoxic activity and antiarrhythmic effects [ 1 , 2 , 3 , 4 ]. As sources of bioactive substance, fungi are now considered as efficient producers of biologically active and chemically novel compounds.…”