title: Synthesis and antimycobacterial activity of agelasine E and analogs.
abstract: Agelasine E, previously isolated from the marine sponge Agelas nakamurai, has been synthesized for the first time, together with analogs with various terpenoid side chains. Treatment of N6-methoxy-9-methyl-9H-purin-6-amine with allylic bromides gave the desired 7,9-dialkylpurinium salts together with minor amounts of the N6-alkylated isomer. The N6-methoxy group was finally removed reductively. 1H-15N HMBC and 1H-15N HSQC NMR spectroscopy gave additional information on tautomerism and charge delocalization in the purine derivatives studied. The heterocyclic products were screened for activity against Mycobacterium tuberculosis and agelasine analogs carrying a relatively long terpenoid substituent in the purine 7-position and a methoxy group at N-6 were potent inhibitors of bacterial growth. Since agelasine analogs with the geranylgeranyl chain at N-7 exhibited antimicrobial activity, several strategies for synthesis of geometrically pure (2E,6E,10E)-geranylgeranyl bromide from geranyllinalool were evaluated.
authors.affiliation: Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway.
authors.forename: Anne Kristin
authors.initials: AK
authors.lastname: Bakkestuen
authors.forename: Lise-Lotte
authors.initials: LL
authors.lastname: Gundersen
authors.forename: Dirk
authors.initials: D
authors.lastname: Petersen
authors.forename: Bibigul T
authors.initials: BT
authors.lastname: Utenova
authors.forename: Anders
authors.initials: A
authors.lastname: Vik
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes