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

Abstract

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 BF2 group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al2O3) or silica (SiO2) 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.

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin

“…(iii) Removal of BF 2 with alumina to recover the β-keto-enol function of the curcuminoid (3). The synthetic method was adequate for the synthesis of ligands in good (Dimethoxycurcumin-BF 2 (2), 85%) to excellent (DiMeOC (3), 90%) yields, as reported previously [24,55]. The spectral information of the precursor (2) and ligands (3) were confirmed by infrared (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR).…”

“…Dimethoxycurcumin (3) was synthesized according to the "click and unclick chemistry" approach for the synthesis of curcuminoids [55], where the following simple three-step method was used: (i) Synthesis of synthon (1) with 2,4-pentanedione and BF 3 •THF, which avoids the Knoevenagel reaction by activating the methyl groups. (ii) Condensation of 2 moles of 3,4-dimethoxybenzaldehyde with synthon (1).…”

Curcumin I-SMA nanomicelles as promising therapeutic tool to tackle bacterial infections

“…Obtained data are in agreement with those reported in literature. 36 1 H NMR (200 MHz, DMSO- d 6 ): δ 9.69 (s, 2H, 2 × OH), 7.55 (d, J = 16.0 Hz, 2H, 2 × CH = CHCO), 7.32 (s, 2H, aromatic), 7.16 (dd, J = 8.0, 2.0 Hz, 2H, aromatic), 6.84–6.72 (m, 4H, aromatic + 2 × CH = CHCO), 6.05 (s, 1H, COCH = COH), 3.84 (s, 6H, 2 × OCH 3 ); 13 C NMR (50 MHz, DMSO- d 6 ): δ 183.23, 149.37, 148.00, 140.74, 126.33, 123.18, 121.09, 115.71, 111.31, 100.89, 55.70.…”

The Homoleptic Curcumin–Copper Single Crystal (ML2): A Long Awaited Breakthrough in the Field of Curcumin Metal Complexes

“…Anhydrous copper (II) acetate was available commercially and purchased from Sigma-Aldrich. Pure curcumin was obtained from synthesis as previously reported [ 74 ]. The solvents were HPLC grade from Sigma-Aldrich.…”