Synthesis and antifungal activities of 3-substituted phthalide derivatives

Abstract

In order to obtain novel bioactive compounds with significant antifungal activities, two series of 3-substituted phthalide derivatives were designed and synthesized via reduction, bromine substitution, and etherification. In addition, the antifungal activities of all target compounds against nine phytopathogenic fungi in vitro were tested by using the mycelial growth rate method at the concentration of 50 μg mL−1. Preliminary bioassay tests showed that some compounds exhibited more potent antifungal activities as compared with hymexazol. The preliminary structure-activity relationships (SARs) of all target compounds were also investigated.

Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-n-Butylidenephthalide

“…Considering the dependence between the structure and fungistatic activity, available data focuses on preliminary structure-activity tests of more complex 3-substituted phthalides against selected phytopathogens. It has been stated that -OH and -NH 2 groups incorporated in the benzene ring may increase the antifungal activity of phthalides due to the formation of a hydrogen bond with the active site of the pathogen enzyme [ 49 ]. In fact, the lack of the activity of the tested compounds ( 2 ) and ( 3 ) may be explained by the –OH and –OCH 3 groups at the C-3 position.…”

Design, Synthesis and Antifungal Activities of 6‐Substituted 3‐Butylphthalide Derivatives against Phytopathogenic Fungi

“…Finally, in view of azo compounds exhibited good inhibition on bacterial and fungal growth, [17] novel compounds 9a-9g containing an azo group and NBP were designed and synthesized based on combination principles (Scheme 2). The structures of all target compounds were characterized by IR, 1 H-NMR, 13 C-NMR and HR-MS.…”

“…Natural products represent a rich source for the discovery and development of novel fungicides either for direct application or structure modification [9] . In continuation of our work on the discovery and development of compounds with superior antifungal activity, [10–14] and in consideration of NBP has the similar structural skeleton to ( Z )‐ligustilide and ( Z )‐butylidenephthalide, herein we selected the natural product of 3‐butylphthalide (NBP) as the lead compound, a series of 6‐substitued NBP derivatives were designed, synthesized and evaluated for their antifungal activities against nine phytopathogenic fungi in vitro .…”

N-{2-[(3-Oxo-1,3-dihydro-2-benzofuran-1-yl)acetyl]phenyl}acetamide

“…2-Benzofuran-1(3H)-ones or isobenzofuranones (also known as phthalides) are considered privileged scaffolds, owing to their wide range of biological properties. More precisely, some phthalide derivatives have been evaluated as antioxidant 1 [1], anti-HIV-1 2 [2], antileishmanial 3 [3] and antifungal 4 [4] while other phthalides are known for their herbicidal properties 5 [5] (Figure 1).…”

“…2-Benzofuran-1(3H)-ones or isobenzofuranones (also known as phthalides) are considered privileged scaffolds, owing to their wide range of biological properties. More precisely, some phthalide derivatives have been evaluated as antioxidant 1 [1], anti-HIV-1 2 [2], antileishmanial 3 [3] and antifungal 4 [4] while other phthalides are known for their herbicidal properties 5 [5] (Figure 1). Additionally, phthalide derivatives are important intermediates in the synthesis of other relevant heterocyclic systems, as is the case for 2,3-dihydro-1H-isoindol-1-one derivatives, which are another type of unique molecules [6][7][8][9] (Scheme 1).…”