A series of new and known geranylated phenol/methoxyphenol derivatives has been tested in vitro as inhibitor agents of mycelial growth of Phytophthora cinnamomi. The activity of tested compounds is correlated with the nature, number, and position of the substituent group on the aromatic ring. Results indicate that the most active geranylated derivatives are those having two hydroxyl groups (or one –OH and one –OCH₃) attached to the aromatic ring. Interestingly, these derivatives are as active as Metalaxil^®, a commonly used commercial fungicide. Thus, our results suggest that some of these compounds might be of agricultural interest due to their potential use as fungicides against P. cinnamomi. The effect of structure on fungicide activity is discussed in terms of electronic distribution on both the aromatic ring and side geranyl chain. All tested compounds have been synthesized by direct coupling of geraniol and the respective phenol. Interestingly, new digeranylated derivatives were obtained by increasing the reaction time.

The inhibitory effects on the mycelial growth of plant pathogen Botritys cinerea have been evaluated for a series of geranylphenols substituted with one, two and three methoxy groups in the aromatic ring. The results show that the antifungal activity depends on the structure of the geranylphenols, increasing from 40% to 90% by increasing the number of methoxy groups. On the other hand, the acetylation of the –OH group induces a change of activity that depends on the number of methoxy groups. The biological activity of digeranyl derivatives is lower than that exhibited by the respective monogeranyl compound. All tested geranylphenols have been synthesized by direct coupling of geraniol and the respective phenol. The effect of solvent on yields and product distribution is discussed. For monomethoxyphenols the reaction gives better yields when acetonitrile is used as a solvent and AgNO₃ is used as a secondary catalyst. However, for di- and trimethoxyphenols the reaction proceeds only in dioxane.

Geranylated hydroquinones and other geranylated compounds isolated from Aplydium species have shown interesting biological activities. This fact has prompted a number of studies where geranylated phenol derivatives have been synthesized in order to assay their bioactivities. In this work, we report the synthesis of a series of new hydrated geranylphenols using two different synthetic approaches and their inhibitory effects on the mycelial growth of Botrytis cinerea. Five new hydrated geranylphenols were obtained by direct coupling reaction between geraniol and phenol in dioxane/water and using BF₃·Et₂O as the catalyst or by the reaction of a geranylated phenol with BF₃·Et₂O. Two new geranylated quinones were also obtained. The synthesis and structural elucidation of all new compounds is presented. All hydrated geranylphenols efficiently inhibit the mycelial growth of B. cinerea. Their activity is higher than that observed for non-hydrated compounds. These results indicate that structural modification on the geranyl chain brings about an enhancement of the inhibition effect of geranylated phenol derivatives.

Botrytis cinerea is a ubiquitous fungus that affects hundreds of plants, resulting in economic losses to the horticulture and fruit industry. The search for new antifungal agents is a matter of current interest. Thus, in this work a series of geranylated phenols in which the side alkyl chain has been hydrated have been synthesized, and their activity against B. cinerea has been evaluated. The coupling of phenol and geraniol has been accomplished under microwave irradiation obtaining the highest reaction yields in the shortest reaction times. Hydration of the side chain was carried out in dioxane with p-toluenesulfonic acid polymer-bound as the catalyst. All synthesized compounds were tested against B. cinerea using the growth inhibition assay and EC₅₀ values were determined. The results show that activity depends on the number and nature of functional groups in the phenol ring and hydration degree of the geranyl chain. The most active compound is 1,4-dihydroquinone with one hydroxyl group attached at the end of the alkyl chain. Results from a molecular docking study suggest that hydroxyl groups in the phenol ring and alkyl chain are important in the binding of compounds to the active site, and that the experimental antifungal activity correlates with the number of H-bond that can be formed in the binding site.