title: Synthesis of sugars embodying conjugated carbonyl systems and related triazole derivatives from carboxymethyl glycoside lactones. Evaluation of their antimicrobial activity and toxicity.
abstract: The synthesis of a series of pyranoid derivatives comprising a conjugated carbonyl function and related triazole derivatives, structurally suitable for bioactivity evaluation, was achieved in few steps starting from readily available carboxymethyl glycoside lactones (CMGL). 3-Enopyranosid-2-uloses were generated by oxidation/elimination of tri-O-acylated 2-hydroxy pyranosides. Subsequent Wittig olefination provided stereoselectively 2-C-branched-chain conjugated dienepyranosides with (E)-configuration around the exocyclic double bond. A heterogeneous CuI/Amberlyst-catalyzed 'click' chemistry protocol was used to convert glycosides bearing a propargyl moiety into the corresponding 1,2,3-triazoles. These new molecules were screened for their in vitro antibacterial and antifungal activities and those containing conjugated carbonyl systems demonstrated the best efficacy. (N-Dodecylcarbamoyl)methyl enone glycerosides were the most active ones among the enones tested. The α-anomer displayed very strong activities against Bacillus cereus and Bacillus subtilis and strong activity toward Enterococcus faecalis and the fungal pathogen Penicillium aurantiogriseum. The corresponding β-anomer presented a very strong inhibitory effect against two fungal species (Aspergillus niger and P. aurantiogriseum). (N-Dodecyl-/N-propargyl/or N-benzylcarbamoyl)methyl dienepyranosides exhibited selectively a strong activity toward E. faecalis. Further acute toxicity evaluation indicated low toxic effect of the (N-dodecylcarbamoyl)methyl enone glyceroside α-anomer and of the carbamoylmethyl dienepyranosides N-protected with propargyl or benzyl groups.
authors.affiliation: Universidade de Lisboa, Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Portugal.
authors.forename: Nuno M
authors.initials: NM
authors.lastname: Xavier
authors.forename: Margarida
authors.initials: M
authors.lastname: Goulart
authors.forename: Ana
authors.initials: A
authors.lastname: Neves
authors.forename: Jorge
authors.initials: J
authors.lastname: Justino
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chambert
authors.forename: Amélia P
authors.initials: AP
authors.lastname: Rauter
authors.forename: Yves
authors.initials: Y
authors.lastname: Queneau
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D002241:Carbohydrates / Q000737:chemistry*; D045744:Cell Line, Tumor; D057930:Click Chemistry; D004353:Drug Evaluation, Preclinical; D005658:Fungi / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry*; D051379:Mice; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D000935:Antifungal Agents; D002241:Carbohydrates; D006027:Glycosides; D007783:Lactones; D014230:Triazoles