Synthesis of norbornane bisether antibiotics via silver-mediated alkylation

A small series of norbornane bisether diguanidines have been synthesized and evaluated as antibacterial agents. The key transformation-bisalkylation of norbornane diol 6-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, 16g and 16h) exhibited antibiotic activity. For example, compound 16d was active against a broad range of bacteria including Pseudomonas aeruginosa (MIC = 8 µg/mL), Escherichia coli (MIC = 8 µg/mL) and methicillin-resistant Staphylococcus aureus (MIC = 8 µg/mL).

Nitrile functionalized methimazole-based ionic liquids

The alkylation reaction of 2-mercapto-1-methylimidazole 1b with 2-chloroacetonitrile and 2-chloropropionitrile produced S-alkyl methimazole chlorides 2a and 2b which were subjected to anion metathesis with lithium bis(trifluoromethanesulfonyl)amide, LiNTf2, to afford nitrile functionalized methimazole-based room temperature ionic liquids 3a and 3b in 94% and 89% yields, respectively. Ionic liquids 3a and 3b have reasonably wide electrochemical windows. The efficient extraction of Ag+ from aqueous media into 3a and 3b is also reported.