Enzymatic Synthesis of Austroeupatol Esters with Enhanced Antiprotozoal Activity

Austroeupatol, the principal diterpene isolated from the invasive shrub <i>Austroeupatorium inulifolium</i>, holds promise for structural diversification and biological assessment of its derivatives due to its abundant availability and high yield isolation. We propose an efficient enzymatic synthesis of a series of austroeupatol esters derived from aliphatic and heterocyclic carboxylic acids. Systematic optimization of reaction parameters, including enzyme type and quantity, acylating agent amount, solvent, and temperature, was conducted. <i>Thermomyces lanuginosus</i> lipase in cyclohexane at 55 °C, yielded esters with favorable conversion rates. Through enzymatic catalysis, mono- and diacylated derivatives were obtained, with a diacylation–monoacylation ratio influenced by temperature and acylating agent amount. The antiprotozoal activity of austroeupatol and all synthesized derivatives was evaluated, observing that acylation improved it. The 19-valeroyl, 19-indolylpropyl, and 19-octyl derivatives were the most potent compounds against <i>Trypanosoma cruzi</i> and <i>Leishmania infantum</i>, highlighting this approach as a valuable method for synthesizing austroeupatol derivatives as potential antiparasitic agents.