Synthesis and Antifungal Activities of Myristic Acid Analogs

Myristic acid analogs that are putative inhibitors of N‐myristoyl‐transferase were tested in vitro for activity against yeasts (Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans) and filamentous fungi (Aspergillus niger). Several (±)‐2‐halotetradecanoic acids including (±)‐2‐bromotetradecanoic acid (14c) exhibited potent activity against C. albicans (MIC = 39 μM). C. neoformans (MIC = 20 μM), S. cerevisiae (MIC = 10 μM), and A. niger (MIC < 42 μM) in RPMI 1640 media. Improved synthetic methods have been developed for the synthesis of 12‐fluorododecanoic acid (12a) and 12‐chlorododecanoic acid (12c). Three novel fatty acids, 12‐chloro‐4‐oxadodecanoic acid (8a), 12‐phenoxydodecanoic acid (12i), and 11‐(4‐iodophenoxy)undecanoic acid (13d) were also synthesized and tested.