Synthesis and anthelmintic activity of thioamide analogues of cyclic octadepsipeptides such as PF1022A

The tetra- and mono-thionated cyclic octadepsipeptides represent novel cycl ic octadepsipeptide derivatives with broad-spectrum activity against parasi tic nematodes in mice and sheep. Some of these show better activity than th e potent natural anthelmintic cyclic octadepsipeptide PF1022A against Hymen olepis nana, Heterakis spumosa and Trichinella spiralis larvae in mice. In particular, they show improved efficacy against Haemonchus contortus and Tr ichostrongylus colubriformis in sheep compared with PF1022A. Here we report on two different and simple synthetic pathways for this new class of thion ated cyclic octadepsipeptides. (C) 2001 Society of Chemical Industry