The use of biological catalysts, such as lipases, instead of more conventional synthetic methods can, in certain cases, provide superior selectivity and permit the selective functionalization of molecules. The utilization of enzymes is also advantageous due to their low environmental impact and lack of toxicity in the concentrations used. Lipases (EC 3.1.1.3), which are part of the hydrolase family, have already been employed for the modification of terpenoids, as they are capable of executing acylation reactions (esterification, transesterification) on alcohol functions. Commercial lipases, and particularly the lipase B from Candida antarctica, have demonstrated remarkable versatility and robustness, and can be utilized to modify a large variety of substrates. Among the thousands of characterized terpenoid compounds, it is noteworthy that a primary allyl alcohol moiety is commonly observed within the terpene family. This represents a promising starting point for the addition of side chains or various linkers, as already described in the literature with other semi-synthetic ester derivatives of sesquiterpene lactones (STLs), such as helenalin. In this context, the strategy discussed herein consists of utilizing immobilized lipases to introduce ester chains onto STLs, with the goal of creating novel derivatives and modulating certain properties of these compounds (e.g., lipophilicity). We sought to develop a methodology which could be conveniently applied to a plethora of terpenoid compounds, thus paving the way for the synthesis of numerous novel semi-synthetic derivatives. For this study, Novozym 435 (immobilized CAL-B) was chosen due to its successful track record in ester synthesis, as well as the straightforward process required to isolate it from the reaction medium (simple filtration). Despite the enzyme's widespread use across various conditions and substrates, no study to date has reported its application in synthesizing STL esters. Furthermore, the specific STLs selected for this article have not been described in any existing literature as having undergone enzymatic modification. STLs from chicory have a limited commercial availability and their high cost makes high-scale studies difficult. Therefore, we opted to begin with a simpler model compound, featuring an allyl-type primary alcohol moiety similar to the one present in our STL targets, ensuring functional conditions for our enzyme. The monoterpenoid (S)-perillyl alcohol (POH) was then selected as a model compound to set up our reaction conditions, mainly due to the presence of the allyl alcohol moiety similar to the one in STLs, as well as its good commercial availability. This cyclic monoterpenoid derives from D-limonene and can be found in Perilla frutescens and several essential oils from plants such as peppermint, spearmint, sage, lemongrass, lavandin, wild bergamot, gingergrass, savin, caraway and celery seeds, cherries and cranberries. In addition to its role as a model substrate for our study, it has already attracted attention of the pharmaceutical community as a potential anticancer agent for the treatment of ovarian, prostate, breast, pancreatic, lung and colorectal cancer. However, recent studies have shown that brain tumors might be one of the most promising targets for perilyl alcohol, particularly via intranasal administration, given its ability to penetrate the Blood-Brain-Barrier. As a result, ester derivatives of perillyl alcohol such as NEO218 and NEO212 have been patented for such pharmaceutical applications, making this substrate a second interesting target for our study. Additionally, the lipase-catalyzed synthesis of perillyl alcohol derivates has also been described in the literature, mainly the acylation with long chain fatty acids and the preparation of perillyl beta-D-glucopyranoside fatty esters (Figure .). Perillyl esters were prepared by Xanthakis et al. using Novozym 435 (40 mg, 167 mM POH, 167 mM acyl donor at 50 °C) with varying yields going from 5.6 % (propionic acid) to 81.5 % (decanoic acid) and 67.5 % for the glycoside derivative (30 mM POH, 100 mM vinyl laureate at 50 °C). This gave us hope that we could find convenient esterification conditions for POH with the enzyme we had selected. In terms of acyl donors, our strategy involved starting with the simplest compound and then gradually increasing the complexity of the acyl chain by modifying the characteristics of its substituents (length and functional groups). Consequently, we began by synthesizing the simplest ester derivative, a methyl ester. Given that the nature of the acyl donor can significantly influence the final esterification yield, both thermodynamically and in terms of the capacity of the enzyme to execute the desired reaction, we chose to employ the synthesis of the acetyl ester as a benchmark reaction. This allowed us to compare the reactivity of two commonly used acyl donors: vinyl acetate and acetic acid.