Natural cyclopeptides as leads for novel pesticides: tentoxin and destruxin

Difficulties in synthesis make natural cyclopeptides challenging targets for chemists. Our interest focused on two natural toxic cyclopeptide series produced by pathogenic fungi: tentoxin, [cyclo-(N-MeAla¹-Leu²-N-Meδ^zPhe³-Gly⁴)] and the destruxins [cyclo-(Pro¹-Ile²-N-MeVal³-N-MeAla⁴-β-Ala⁵-HA⁶)]. The total syntheses of these two bioactive series were optimised, and several analogues were designed and synthesised to establish structure–activity relationships. The importance of synthetic analogues in the identification of molecular targets and the explanation of mechanisms of action was demonstrated. Such systematic investigations can determine the crucial features responsible for the activity of the natural compound and help the design of more powerful or more selective products. © 1998 SCI.