A synthesis of curcumin and related compounds

Pabon, H. J. J.

doi:10.1002/recl.19640830407

Cited by 316 publications

(289 citation statements)

References 6 publications

Supporting

Mentioning

276

Contrasting

Unclassified

Order By: Relevance

“…Synthesis of 4Ј,4Љ-Dimethoxycurcumin-The procedure followed the method of Pabon for the synthesis of curcumin (26). Boron oxide (B 2 O 3 ), 0.5 g (7 mmol), was mixed with 1 g (10 mmol) of acetylacetone and stirred for 3 h to give a thick white suspension.…”

Section: Methodsmentioning

confidence: 99%

Autoxidative and Cyclooxygenase-2 Catalyzed Transformation of the Dietary Chemopreventive Agent Curcumin

Grießer

Pistis

Suzuki

et al. 2011

Journal of Biological Chemistry

134

196

View full text Add to dashboard Cite

The efficacy of the diphenol curcumin as a cancer chemopreventive agent is limited by its chemical and metabolic instability. Non-enzymatic degradation has been described to yield vanillin, ferulic acid, and feruloylmethane through cleavage of the heptadienone chain connecting the phenolic rings. Here we provide evidence for an alternative mechanism, resulting in autoxidative cyclization of the heptadienone moiety as a major pathway of degradation. Autoxidative transformation of curcumin was pH-dependent with the highest rate at pH 8 (2.2 M/min) and associated with stoichiometric uptake of O 2 . Oxidation was also catalyzed by recombinant cyclooxygenase-2 (COX-2) (50 nM; 7.5 M/min), and the rate was increased ≈10-fold by the addition of 300 M H 2 O 2 . The COX-2 catalyzed transformation was inhibited by acetaminophen but not indomethacin, suggesting catalysis occurred by the peroxidase activity. We propose a mechanism of enzymatic or autoxidative hydrogen abstraction from a phenolic hydroxyl to give a quinone methide and a delocalized radical in the heptadienone chain that undergoes 5-exo cyclization and oxygenation. Hydration of the quinone methide (measured by the incorporation of O-18 from H 2 18 O) and rearrangement under loss of water gives the final dioxygenated bicyclopentadione product. When curcumin was added to RAW264.7 cells, the bicyclopentadione was increased 1.8-fold in cells activated by LPS; vanillin and other putative cleavage products were negligible. Oxidation to a reactive quinone methide is the mechanistic basis of many phenolic anti-cancer drugs. It is possible, therefore, that oxidative transformation of curcumin, a prominent but previously unrecognized reaction, contributes to its cancer chemopreventive activity.The yellow plant phenolic pigment curcumin shows a remarkable ability to affect a wide variety of signaling pathways that are dysregulated during tumorigenesis, including proliferation, invasion, apoptosis, and cell cycle checkpoints (1).Altogether more than one hundred molecular targets of curcumin have been identified using in vitro cell culture-based assays (2). The diversity of biological effects of curcumin has been attributed to its ability to act as an antioxidant, anti-inflammatory, and anti-viral agent (3). As a consequence of promising in vitro results, several clinical trials have been initiated to investigate the effect of dietary curcumin in the prevention of inflammatory bowel disease, colon, and pancreatic cancer, and Alzheimer Disease, among others (3).Prior to the more recent interest in its chemopreventive properties, curcumin was being considered as a food coloring agent but its chemical and photochemical instability prevented widespread application. Light-induced degradation of curcumin in organic solvents results in cleavage of the heptadienone chain, and the most abundant products have been identified as vanillin, ferulic aldehyde, ferulic acid, and feruloylmethane (4, 5). The same products have been observed as degradation products of curcumin in aqueous buf...

show abstract

Section: Methodsmentioning

confidence: 99%

Autoxidative and Cyclooxygenase-2 Catalyzed Transformation of the Dietary Chemopreventive Agent Curcumin

Grießer

Pistis

Suzuki

et al. 2011

Journal of Biological Chemistry

134

196

View full text Add to dashboard Cite

show abstract

“…This difficulty of separation has led to several efforts to synthesize the compound. For this study, pure curcumin was synthesized according to the method of Pabon 17 that involves condensation of vanillin and 2,4 pentanedione, followed by purification by crystallization from ethyl acetate/MeOH at 4°C (97% pure by high-performance liquid chromatography [HPLC] analysis; high resolution mass spectrometry calculated for C 21 H 20 O 6 H 369.1333, found 369.1324).…”

Section: Synthesis Of Curcuminmentioning

confidence: 99%

Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

Ghosh¹,

Banerjee²,

Bhandary³

et al. 2014

IJN

View full text Add to dashboard Cite

Aim The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results The nanopreparation was found to be non-toxic and had a particle size distribution of 20–50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration [IC 50 ]: 0.5 μM) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC 50 : 5 μM). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei -infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system.

show abstract

“…The weak N-O bond of isoxazole ring is easily cleaved into b-aminoenone by either catalytic hydrogenolysis with platinum or palladium and Raney nickel under normal pressure and temperature 16,17 or by treatment with transition metal carbonyls such as molybdenum hexacarbonyl [Mo(CO) 6 ]. 18 To avoid catalytic hydrogenation at the two styryl groups, 3,5-bisstyrylisoxazoles 2a-f were treated with molybdenum hexacarbonyl in moist acetonitrile at reflux temperature.…”

Section: Resultsmentioning

confidence: 99%

“…Synthetic symmetrical curcumin derivatives reported in literature [2][3][4][5] were obtained from Pabons procedure. 6 Unsymmetrical curcumin derivatives, on the other hand, were synthesized by solid-phase synthetic strategy. 7 Both syntheses proceeded through acetylacetone-boric anhydride complex which methyl terminals of this complex were allowed to undergo aldol condensation.…”

Section: Introductionmentioning

confidence: 99%

Reductive ring opening of 3,5-bis(2-arylethenyl)isoxazoles with molybdenum hexacarbonyl: A novel route to symmetrical and unsymmetrical curcumin derivatives

Hahnvajanawong

Thaima²,

Tearavarich³

et al. 2016

Orient. J. Chem

View full text Add to dashboard Cite

Curcumin derivatives were successfully synthesized from 3,5-dimethylisoxazole by lateral metalation and condensation with various aromatic aldehydes sequentially at C 5 -and C 3 -methyl groups. After dehydration, further transformation of isoxazole ring to b-diketone moiety was accomplished by reductive ring opening using molybdenum hexacarbonyl [Mo(CO) 6 ] and subsequent simple acidic hydrolysis.

show abstract

A synthesis of curcumin and related compounds

Abstract: Curcumin has been prepared in 80% yield from vanillin and acetylacetone/BaOs in the presence of tri-sec. butyl borate and butylamine. The reaction was carried out in ethyl acetate at room temperature. Eight compounds related to curcumin have also been synthesized.

Cited by 316 publications

References 6 publications

Autoxidative and Cyclooxygenase-2 Catalyzed Transformation of the Dietary Chemopreventive Agent Curcumin

Autoxidative and Cyclooxygenase-2 Catalyzed Transformation of the Dietary Chemopreventive Agent Curcumin

Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

Reductive ring opening of 3,5-bis(2-arylethenyl)isoxazoles with molybdenum hexacarbonyl: A novel route to symmetrical and unsymmetrical curcumin derivatives

Contact Info

Product

Resources

About