Curcumin, a natural polyphenolic compound with broad pharmacological potential, continues to attract interest for its diverse bioactivities. However, its clinical application is hindered by poor stability and low bioavailability. To address these limitations, researchers have focused on the design and synthesis of mono-carbonyl curcumin analogues. This review provides a comprehensive analysis of synthetic methodologies for α,β-unsaturated mono-carbonyl curcumin analogues, critically examining classical aldol and Claisen-Schmidt condensation reactions under both acidand base-catalysed conditions. The suitability of these conditions for various substituents, including methoxy, alkyl, hydroxy, halogen, and pyrazole rings, is discussed alongside key reaction parameters such as solvent choice, temperature, catalyst type, and reaction time. Acid catalysis is generally more effective for hydroxy-substituted analogues, while base catalysis favours methoxy and alkyl analogues. In addition, this review highlights recent advances in green and sustainable synthetic strategies such as microwave-assisted reactions, solvent-free conditions, ionic liquids, and recyclable heterogeneous catalysts that improve reaction efficiency while minimising environmental impacts. The influence of electronic and steric substituent effects, as well as practical considerations for scalability and reproducibility, is discussed to support effective analogue design. By bridging traditional synthetic approaches with sustainable strategies, this review offers updated and practical insights for researchers working on the development of more stable and bioavailable curcumin analogues for therapeutic use.
Loh et al. (Wed,) studied this question.
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