title: Synthesis of Norbornane Bisether Antibiotics via Silver-mediated Alkylation.
abstract: A small series of norbornane bisether diguanidines have been synthesized and evaluated as antibacterial agents. The key transformation-bisalkylation of norbornane diol6-was not successful using Williamson methodology but has been accomplished using Ag2O mediated alkylation. Further functionalization to incorporate two guanidinium groups gave rise to a series of structurally rigid cationic amphiphiles; several of which (16d, 16gand16h) exhibited antibiotic activity. For example, compound16dwas active against a broad range of bacteria includingPseudomonas aeruginosa(MIC = 8 µg/mL),Escherichia coli(MIC = 8 µg/mL) and methicillin-resistantStaphylococcus aureus(MIC = 8 µg/mL).
authors.affiliation: Research Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia.
authors.forename: Shane M
authors.initials: SM
authors.lastname: Hickey
authors.affiliation: Research Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia.
authors.forename: Trent D
authors.initials: TD
authors.lastname: Ashton
authors.affiliation: Bio21 Institute, School of Chemistry, University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: White
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Royal Parade, Parkville, Victoria, 3052, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Royal Parade, Parkville, Victoria, 3052, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Royal Parade, Parkville, Victoria, 3052, Australia.
authors.forename: Heidi Y
authors.initials: HY
authors.lastname: Yu
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
authors.forename: Alysha G
authors.initials: AG
authors.lastname: Elliott
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Butler
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
authors.forename: Johnny X
authors.initials: JX
authors.lastname: Huang
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: Research Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Pfeffer