Design, Synthesis, and Antifungal Activity of Isochroman-Fused Coumarins against Rhizoctonia solani

We dedicate this article to the fond memory of our beloved Late Prof. Ashok K. Prasad

Abstract

This study presents the synthesis and antifungal assessment of novel isochroman-fused coumarin derivatives against Rhizoctonia solani. The compounds were synthesized using an efficient and environmentally benign approach and demonstrated strong in silico binding affinity to CYP51. In vitro assays further confirmed their antifungal activity, with one compound exhibiting the highest potency, achieving an ED₅₀ value of 3.59 μM. These findings underscore the potential of isochroman-fused coumarins as eco-friendly rice sheath blight control agents.

Key words

isochroman-fused coumarins - antifungal agents - Rhizoctonia solani - palladium catalysis - in silico

Publication History

Received: 10 March 2025

Accepted after revision: 19 May 2025

Accepted Manuscript online:
20 May 2025

Article published online:
02 July 2025

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• 38 General Procedure for the Synthesis of Isochroman-Fused Coumarins 4a–i 4-Hydroxy coumarins 1a–h (1 equiv) and 2-bromobenzyl bromide 2a,b (1 equiv) were dissolved in propylene carbonate (5 mL) in the presence of potassium carbonate base (3 equiv) and 10 mol% PdCl₂ as a catalyst in a 50 mL round-bottomed flask. The reaction mixture stirred for 4 h at 120 °C. Chloroform was then used to extract the resultant reaction mixture (3 × 30 mL) after the indication of completion of the reaction by TLC. The combined extracts were washed with brine solution, then dried using anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure under a vacuum resulting in the isolation of the crude product. The crude product thus obtained was purified by silica gel chromatography using ethyl acetate in petroleum ether as a gradient solvent system. The separated pure products were characterized by ¹H, ¹³C NMR spectroscopy, mass spectroscopy, and IR spectroscopy.
• 39 6H,11H-Isochromeno[4,3-c]chromen-11-one (4a) It was obtained as a white solid in 68% yield using 5% ethyl acetate in petroleum ether as an eluent, mp 105–107 °C; R _ƒ = 0.4 (8% ethyl acetate in petroleum ether). IR (KBr): 1702, 1612, 1490, 1332, 1286, 1091, 913, 750 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.56 (1 H, d, J = 7.9 Hz), 7.86–7.88 (1 H, m), 7.57 (1 H, t, J = 8.4 Hz), 7.42 (1 H, t, J = 7.6 Hz), 7.32 (3 H, dt, J = 15.2, 7.7 Hz), 7.13 (1 H, d, J = 7.4 Hz), 5.41 (2 H, s). ¹³C NMR (100.6 MHz, CDCl₃): δ = 161.3, 160.3, 153.0, 132.6, 129.2, 128.4, 127.5, 126.8, 125.0, 124.2, 124.1, 123.2, 116.7, 115.3, 102.8, 69.9. HRMS (ESI): m/z calcd for C₁₆H₁₁O₃ [M + H]⁺: 251.0703; found: 251.0705.