High Yield Synthesis of Curcumin and Symmetric Curcuminoids: A "Click" and "Unclick" Chemistry Approach

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 1; p. 289
• Main Authors: Obregón-Mendoza, Marco A, Meza-Morales, William, Alvarez-Ricardo, Yair, Estévez-Carmona, M Mirian, Enríquez, Raúl G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-12-2022; MDPI
• Subjects: Acetylacetone; Adsorption; Aluminum; Aluminum hydroxide; Aluminum oxide; Alzheimer's disease; BF3·THF; bis-demethoxycurcumin; Boron; Chemistry; Chromatography; Cleavage; Crystallization; Curcuma longa; Curcumin; diferuloylmethane; Efficiency; Metal oxides; Michael acceptor; Reagents; Silica; Silicon dioxide; alumina; Michael acceptor; Curcuma longa; bis-demethoxycurcumin; BF3·THF; diferuloylmethane; curcumin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28010289

The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF
group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al
O
) or silica (SiO
) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms "click" and "unclick" applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80-92% yield), in pure form and excellent yields.