Design, Synthesis and Antifungal Activity of Coumarin Ring-Opening Derivatives

Abstract

Based on our initial design, we synthesized two series of coumarin ring-opening derivatives by the reactions of hydrolysis and methylation. Results of antifungal screening in vitro showed that the target compounds exhibited potent activity against the six common pathogenic fungi. Compounds 6b, 6e, 6g, 6i, 7b and 7c were identified as the most active ones, and the EC 50 values of these active compounds were further tested. Compared to the commonly used fungicide Azoxystrobin (0.0884 µM), compounds 6b (0.0544 µM) and 6e (0.0823 µM) displayed improved activity against Botrytis cinerea.

Novel Fluorinated 7-Hydroxycoumarin Derivatives Containing an Oxime Ether Moiety: Design, Synthesis, Crystal Structure and Biological Evaluation

“…The test strains Botrytis cinerea ( B. cinerea ), Alternaria solani ( A. solani ), Gibberella zeae ( G. zeae ), Rhizoctorzia solani ( R. solani ), Colletotrichum orbiculare ( C. orbiculare ) and Alternaria alternata ( A. alternata ) were provided by the State & Local Joint Engineering Research Center of Green Pesticide Invention and Application at Nanjing Agricultural University. The antifungal activities of target compounds were implemented at an equivalent concentration of 100 μg/mL using mycelia growth inhibitory rate methods according to our published literature [ 16 , 37 ]. Every title compound (30.0 mg) was dissolved in 0.6mL dimethyl sulfoxide and evenly mixed with 299.4 mL of PSA (potato sucrose agar) medium.…”

“…The corresponding synthesis methods and pharmacological activities were also well reported, such as Osthole, Coumoxystrobin and Warfarin ( Figure 1 ). Employing Osthole as a lead structure, our group synthesized a series of coumarin derivatives against the phytopathogenic fungi effectively ( Figure 2 ), including coumarin [8,7- e ][1,3]oxazine [ 13 ], furo[3,2- c ]coumarin [ 14 ], pyrano[3,2- c ]chromene-2,5-dione [ 14 ], coumarin-3-carboxamide derivatives [ 15 ], coumarin ring-opening derivatives [ 16 ] and pyrrole/pyrazole-substituted coumarin derivatives [ 17 ]. Due to the pharmacological diversity of coumarin derivatives, it has been described as one of “privileged scaffolds” [ 18 , 19 ].…”

Design, Synthesis and Antifungal Activity of Psoralen Derivatives

“…To date, in order to decrease toxicity and explore the potential biological activity of linear furanocoumarins there has been accomplished in three different ways: first, using angular furanocoumarins, which on account of their geometry cannot crosslink with DNA; second, blocking of the photo reactive α-pyrone double bond by appropriate substituents or by annelation of an additional aromatic ring; third, incorporating an additional benzene ring between active double bonds of the a-pyrone and furan moiety [ 16 ]. Based on our previous work ( Figure 1 ) [ 12 , 13 , 17 , 18 , 19 , 20 ], a series of different substituted linear furanocoumarins were designed and synthesized by construction of a furan ring on the benzene moiety of coumarin ( Scheme 1 ). To the best of our knowledge, there was less research systematically investigated the antifungal activity of linear furanocoumarins against plant pathogenic fungi.…”

Selectfluor-Enabled C(sp3)–H Alkoxylation of 3-Methylfuranocoumarins

“…1c, 3af′, 3ef′, 3aa−3al, 4bf−4ff, 4ea−4ep, 5, and 6 were synthesized as follows 3-Methyl-8-nitro-4H-furo[3,2-c]chromen-4-one (1c). 20 1c was obtained as a yellow solid (35% yield, 52 mg) after flash chromatography (SiO 2 , petroleum ether/ethyl acetate, 20:1): 1 2-Fluoro-3-isopropoxy-3-methyl-2,3-dihydro-4H-furo[3,2-c]chromen-4-one (3af′) cis Form. 17 3af′ was obtained as a white solid (71% yield, 39.2 mg) after flash chromatography (SiO 2 , petroleum ether/ethyl acetate, 20:1): 1 3-(Methoxymethyl)-4H-furo[3,2-c]chromen-4-one (3aa).…”

“…Undoubtedly, classic fluoroalkoxylation of the 3-methylfuran ring occurred in the presence of Selectfluor and alcohols (Scheme c) . In recent years, the application of Selectfluor as a “fluorine-mediated” functional reagent under transition-metal-free conditions was realized in organic synthesis. , 3-Methylfuranocoumarin is an important pharmaceutical intermediate, and in a continuation of our group’s work on fluorine chemistry and C–H activation, − we envisioned that 3-methylfuranocoumarin and alcohols might provide the C­(sp 3 )–H ethers using Selectfluor under metal-free conditions. Herein, we report our research results (Scheme d).…”