Parasitic nematodes are a major cause of morbidity and mortality in man and also cause widespread loss of food production by
infection of livestock. A milestone in the
chemotherapy of
nematode infections, especially in animals, was the discovery of the
avermectins and
milbemycins during the 1970s. Since the discovery of these highly active
macrolides, reports of potent new classes of
anthelmintics have been scarce. One of the most outstanding recently reported
anthelmintics is the cyclooctadepsipeptide
PF1022A, the most active member of a novel class of
anthelmintic agents. During the past years several total syntheses of
PF1022A and manifold structure-activity relationships have been established. Additionally, the biosynthesis of
PF1022A has been elucidated and intensive investigations into the mode of action of this novel
anthelmintic are underway. Comprehensive studies including
cyclodepsipeptides with smaller ring-sizes, such as the
enniatins, proved the PF1022 family and related
cyclodepsipeptides to be the most promising follow-up candidates for the
avermectins and
milbemycins, which suffer from increasing nematode resistance.