Synthesis of sugars embodying conjugated carbonyl systems and related triazole derivatives from carboxymethyl glycoside lactones. Evaluation of their antimicrobial activity and toxicity |
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Authors: | Xavier Nuno M Goulart Margarida Neves Ana Justino Jorge Chambert Stéphane Rauter Amélia P Queneau Yves |
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Affiliation: | a Universidade de Lisboa, Faculdade de Ciências, Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Campo Grande, Ed. C8, Piso 5, 1749-016 Lisboa, Portugal b INSA-Lyon, Laboratoire de Chimie Organique, Bâtiment J. Verne, 20 av A. Einstein, F—69621 Villeurbanne, France c CNRS, UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université de Lyon, Bâtiment CPE, 43 bd du 11 novembre 1918, F—69622 Villeurbanne, France d Escola Superior Agrária, Instituto Politécnico de Santarém, Complexo Andaluz, Apartado 279, 2001-904 Santarém, Portugal |
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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 ??-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 ??-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 ??-anomer and of the carbamoylmethyl dienepyranosides N-protected with propargyl or benzyl groups. |
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Keywords: | Bicyclic sugar lactones Sugar enones Diene pyranosides 1,2,3-Triazoles Antimicrobial activity |
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