Synthesis of New Hydrated Geranylphenols and in Vitro Antifungal Activity against Botrytis cinerea

Abstract

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.

Synthesis and Fungicidal Activity of Hydrated Geranylated Phenols against Botrytis cinerea

“…Antifungal activities against B. cinerea of all synthesized compounds were evaluated. On the other hand, the effect of chemical modification of the side chain on antifungal activity has received much less attention, i.e., it has been shown that the hydrated derivative of 2-allylphenol exhibits antifungal activity against P. aphanidermatum, V. mali, B. cinerea and R. cereals [16], whereas some hydrated derivatives of geranylated phenols (Figure 2) inhibit the mycelial growth of B. cinerea [14].…”

“…The synthesis of geranylated phenols is well described and generally it proceeds by direct coupling of geraniol with the proper phenol in the presence of BF3•OEt2 as a catalyst and dioxane as solvent [1,9,14,[17][18][19]. Alternatively, BF3•OEt2/AgNO3 has been used as catalyst and acetonitrile as solvent [11,12].…”

“…In previous work, we reported the synthesis of a series of geranylated phenols with different chemical substituents on the aromatic ring (see Figure 1). These compounds exhibited interesting biological activities, such as in vitro cytotoxicity on cancer cell lines [9,10], mycelial growth inhibition of Botrytis cinerea [11][12][13][14] and antifungal activity against Phytophthora cinnamomi [15]. The results indicate that the activity is enhanced mainly by the presence of −OH, -OCH 3 and -OAc functions in the aromatic ring [11][12][13].…”

“…enhanced mainly by the presence of −OH, -OCH3 and -OAc functions in the aromatic ring [11][12][13]. On the other hand, the effect of chemical modification of the side chain on antifungal activity has received much less attention, i.e., it has been shown that the hydrated derivative of 2-allylphenol exhibits antifungal activity against P. aphanidermatum, V. mali, B. cinerea and R. cereals [16], whereas some hydrated derivatives of geranylated phenols (Figure 2) inhibit the mycelial growth of B. cinerea [14]. Thus, the aim of this work is to carry out a systematic study of the effect of ring substitution and hydration of side chain on the activity of geranylated phenols against B. cinerea.…”

Cytotoxic Effect of Geranylphenol Derivatives in the Human Breast Cancer Cell Line MDA-MB-231 and Gastric Cancer Cell Line MKN74

“…Other synthetic geranylphenols, such as 2-geranyl-5methyl resorcinol and 4-geranyl-5-methyl resorcinol ( Figure 1A), showed antimicrobial and antifungal activities [16][17][18][19] . Recently, our research group has developed the synthesis, structural determination and antifungal activity of a series of linear geranylphenols derivatives of 2-geranylhydroquinones, such 2-geranylphloroglucinol ( Figure 1A) [20][21][22][23][24][25][26] .…”