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Sustainable Synthesis of Pyrano[3,2‐c]Chromenes With Dual Antioxidant and Anti‐Inflammatory Activities Using a Recyclable 1,3‐Butanediol/ChCl/Ammonia (B‐DES/NH 3 ) System

Year: 2026

Type: article

Abstract: ABSTRACT Pyrano[3,2‐c]chromenes are of significant interest in both biology and synthetic methodology. In a one‐pot three‐component reaction of 4‐hydroxycoumarin, malononitrile (or 1,3‐dicarbonyl compound), and aldehyde, basic conditions were found to promote the synthesis for the first time, with ammonia identified as the optimal catalyst. A series of choline chloride‐based deep eutectic solvents (DESs) were designed as sustainable media; the 1,3‐butanediol/ChCl/ammonia (B‐DES/NH 3 ) system afforded product 4a in 92% yield and could be recycled over 10 times without substantial loss. Under optimized conditions, 21 pyrano[3,2‐c]chromene derivatives were synthesized. Biological evaluation revealed potent antioxidant activity: derivatives 4p, 4q, 5b , and 5c (derived from natural aldehydes) showed greatly enhanced DPPH and ABTS activity compared to parent aldehydes, while 4a, 4e, 4f, 4h , and 4r exhibited ABTS IC 50 values as low as 1.49 to 2.50 µM. In an LPS‐induced mouse inflammation model, most derivatives significantly suppressed IL‐6 and TNF‐α expression, with 4e, 4h, 4i , and 4k achieving >50% inhibition of both cytokines. These results confirm the promising dual antioxidant and anti‐inflammatory profile of these compounds, particularly 4e and 4h derived from electron‐withdrawing aromatic aldehydes. In summary, an atom‐economical, recyclable, and operationally simple protocol has been developed using the green B‐DES/NH 3 system, yielding compounds with potent dual activities.

Source: ChemistrySelect

DOI: 10.1002/slct.74072