Synthesis of Farnesyloxy- and Drimanyloxy-Arene Scaffold-Based Hybrid Molecules as Antifungals against <i>Botrytis cinerea</i>

There is an increasing interest in the use of biopesticides, which implies the use of living microorganisms, plant and microbial extracts, and natural products isolated from the above-mentioned sources or closely related derivatives. In this regard, 10 farnesyloxy-arenes derivatives (<b>21</b>-<b>25</b>, (±)-<b>26</b>-(±)-<b>30</b>) and 12 drimanyloxyarenes derivatives ((±)-<b>12</b>-(±)-<b>14</b>, (±)-<b>31</b>-(±)-<b>40</b>) were synthesized and tested against the phytopathogenic fungus <i>Botrytis cinerea</i>. In general, the drimanyloxyarenes derivatives were more fungitoxic than their farnesyloxyarene precursors. The most active compounds were (±)-<b>12</b>, (±)-<b>31</b>, and (±)-<b>35</b>, which at a 391 × 10^-5 mg/mL dose, were more active than azoxystrobin, while (±)-<b>12</b> presented an inhibition comparable to that of triclosan. Structure-activity relationships are discussed, as well as the correlation with calculated physicochemical properties such as logP and total polar surface area.