Structure-antifeedant activity relationship of clerodane diterpenoids. Comparative study with withanolides and azadirachtin

A structure-antifeedant activity relationship (SAR) study of clerodane dite rpenoids was carried out. Attention was focused on the feeding-deterrent ac tivities exhibited toward Tenebrio molitor by clerodane diterpenoids and wi thanolides. Azadirachtin was chosen as a reference compound, SAR studies on the clerodane compounds indicate that the stereoelectronic factors are mor e important than the hydrophobic aspects as determinants of antifeedant act ivity. A furan ring in the side chain and a carbonyl alpha,beta-unsaturated (or spiro-epoxide) group appear to be indispensable far the biological res ponse. A conformational study indicate that the optimum interatomic distanc e between these moieties is a range between 9.5 and 10.5 Angstrom. In addit ion, a similar stereoelectronic response was found among withanolides and a zadirachtin. On the basis of these results it is reasonable to imagine a cl osely related chemical mechanism for these compounds.