Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of -Alkyl d- and l-Iminosugars.

In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars - and - based on the one-pot conjugation of both enantiomeric forms of -butyldeoxynojirimycin (NBDNJ) and -nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction was tuned using the established PS-TPP/I/ImH activating system, which provided the desired compounds in high yields (94-96%) by a one-pot procedure. The substantial increase in the lipophilicity of - and - is supposed to improve internalization within the bacterial cell, thereby potentially leading to enhanced antimicrobial properties. However, assays are currently hampered by solubility problems; therefore, alternative administration strategies will need to be devised.