Dillapiol is a naturally occurring methylenedioxyphenyl (MDP) compound that acts as an insecticide synergist comparable in activity to the widely used piperonyl butoxide (PBO). More than thirty synthetic analogs of dillapiol and sesamol were prepared and evaluated for their inhibitory activity in a cloned human Cytochrome P450 3A4 (CYP 3A4) enzyme in order to assess their use as pesticide synergists and to determine the next generation of compounds. These compounds represent a second generation of analogs based on the knowledge gained from compounds prepared and evaluated by a former member of our group. The choice of new structures was also influenced by the surprising and important observations by Dr. Suqi Liu that compound 21 inhibited not only CYP 3A4 but also glutathione-S- transferase (GST). A set of compounds related to 21 were sent to BASF (Durham NC) for evaluation of their synergistic activity, toxicity and persistence in soil studies. In a number of instances these analogs outperformed PBO as synergists even when given at 1:1 synergist: pesticide ratio compared to PBO at 5:1 when tested against a variety of resistant insects in BASF laboratories in the USA, Holland, India and Indonesia. All of the compounds were shown to be non-toxic to animal life. Their half-life in soils was typically less than 10 days. The results obtained form the basis of two BASF - University of Ottawa patent applications. The most potent CYP3A4 inhibitors synthesized as part of this project are the sulfones 15and 15a. These compounds are 107 and 71 times more potent than dillapiol, respectively which has an IC50 of 8.9 ±0.3 µM. The ortho- chlorobenzyl ether 48 was shown to be 74 times more potent than dillapiol. The synthesis of Z02 analogs in which the NH and C (O) substituents of the B unit are in the ortho-, meta- and para-orientation compared to the meta-orientation of Z02 is reported. The bioactivities of these compounds were compared with previously synthesized meta- substituted analogs to determine which of the three orientations, ortho-, meta-, or para-, resulted in the most potent compounds. In vitro bioassay results obtained by the Brown group allow us to draw conclusions on the effects of the structural characteristics necessary for optimization of activity. Results acquired thus far have suggested that both the ortho- or para- substituted analogs have reduced activity relative to the meta- substituted analogs. Replacement of the oxygen in the CD unit by a sulfoxide and sulfone gave compounds with slightly improved inhibition of SOX9 but with still lower activity relative to Z02. The SAR performed in this project did not result in compounds superior to Z02. Nevertheless, the results described in this thesis give guidance for future SAR studies. It is recommended that future synthetic efforts be concentrated on the metaoriented analogs.