Synthesis and Antifungal Activity of Stereoisomers of Mefloquine Analogs.

and are among the most prevalent causes of life-threatening fungal infections globally. The high mortality associated with these infections despite current antifungal therapy highlights the need for new drugs. In our previous work, we demonstrated that an analogue of the clinically used antimalarial mefloquine, (8-chloro-2-(4-chlorophenyl)quinolin-4-yl)(piperidin-2-yl)methanol (), has both antifungal activity and the ability to penetrate the central nervous system. Herein we describe the synthesis and antifungal assay of all four stereoisomers of . All four stereoisomers retain potent antifungal activity with the enantiomers having MIC values of 1 and 4 μg/mL against and respectively, and enantiomers, MIC values of 2 and 8 μg/mL, respectively. These results indicate that the stereochemistry of the piperidine methanol group is not critical for the antifungal properties of and gives guidance to future medicinal chemistry optimization efforts.