Synthesis and biological evaluation of destruxin A and related analogs

This report describes the development of an efficient solid-phase synthesis protocol and adaptation of reported solution phase procedures for the synt hesis of the cyclic depsihexapeptide destruxin A and related analogs. The s olid-phase method described is based on standard Fmoc peptide chemistry, in cluding a new synthetic method for the assembly of the depsi bond-containin g unit. In order to select analogs of destruxin A for synthesis and evaluat ion of insecticidal activity, the work of Hellberg et al., describing a set of Z-descriptors for amino acid side-chains comparing their physicochemica l properties, was utilized. Destruxin A and 27 different analogs with struc tural variations in four residues were synthesized and insecticidal activit y was evaluated via injections into tobacco budworm (Heliothis virescens) l arvae. Several destruxin A analogs were found to be at least as potent as t he native compound.