Technical Abstract: Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a–5g) that mimic the natural products piperideines that were recently identified in the fire ant venom have been synthesized. Compounds 5c–5g with the C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexadecyl-2,3,4,5-tetrahydropyridine) and 5f (6-heptadecyl-2,3,4,5-tetrahydropyridine) being the most active ones. Compound 5e exhibits minimum fungicidal concentrations (MICs) of 3.8, 15.0, 7.5, and 7.5 'g/mL against Cryptococcus neoformans, Candida albicans, C. glabrata, and C. krusei, respectively. The antifungal activities of these compounds appear to be associated with the C-6 side chain length. This study represents the first effort of evaluating antifungal activities of synthetic analogs of the newly identified fire ant venom alkaloids.