Electrosynthesis of 4,4-dimethyl-2-ethoxycarbonyl-5-fluoro-3-thiolanones: highly potent human type II PLA2 inhibitors

Anodic monofluorination of 2-methyl- and 2-benzyl-4,4-dimethyl-2-ethoxy-carbonyl-3-thiolanones 1 and 2 was successfully performed to provide the corresponding 5-fluorinated products 3 and 4, respectively in good yields. The stereoisomeric mixture of 4 was found to possess comparable or even stronger in vitro human type II phospholipase A2 inhibitory activity compared with the known inhibitor, manoalide, and the cis isomer of 4 exhibited higher activity than the trans isomer.