Synthesis and antimicrobial activities of N6-hydroxyagelasine analogs and revision of the structure of ageloximes |
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| Authors: | Britt Paulsen Kim Alex Fredriksen Dirk Petersen Louis Maes An Matheeussen Ali-Oddin Naemi Anne Aamdal Scheie Roger Simm Rui Ma Baojie Wan Scott Franzblau Lise-Lotte Gundersen |
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| Affiliation: | 1. Department of Chemistry, University of Oslo, P.O.Box 1033, Blindern, 0315 Oslo, Norway;2. Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Wilrijk, Belgium;3. Institute of Oral Biology, University of Oslo, P.O. Box 1052, Blindern, 0316 Oslo, Norway;4. Institute for Tuberculosis Research, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL, USA |
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| Abstract: | (+)-N6-Hydroxyagelasine D, the enantiomer of the proposed structure of (?)-ageloxime D, as well as N6-hydroxyagelasine analogs were synthesized by selective N-7 alkylation of N6-[tert-butyl(dimethyl)silyloxy]-9-methyl-9H-purin-6-amine in order to install the terpenoid side chain, followed by fluoride mediated removal of the TBDMS-protecting group. N6-Hydroxyagelasine D and the analog carrying a geranylgeranyl side chain displayed profound antimicrobial activities against several pathogenic bacteria and protozoa and inhibited bacterial biofilm formation. However these compounds were also toxic towards mammalian fibroblast cells (MRC-5). The spectral data of N6-hydroxyagelasine D did not match those reported for ageloxime D before. Hence, a revised structure of ageloxime D was proposed. Basic hydrolysis of agelasine D gave (+)-N-[4-amino-6-(methylamino)pyrimidin-5-yl]-N-copalylformamide, a compound with spectral data in full agreement with those reported for (?)-ageloxime D. |
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| Keywords: | Agelasine Ageloxime Antimicrobial activity Structure elucidation |
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