Total Synthesis of Luteolin

Abstract

Luteolin is a naturally-occurring polyphenolic flavonoid compound which has received considerable attention because of its wide range of biological and pharmacological properties. Efficient methods are reported for preparing luteolin, based on the acylation of 1,3,5-trimethoxybenzene and condensation with 3,4-dimethoxybenzaldehyde or the reaction of 3,4-dimethoxycinnamic acid with 1,3,5-trimethoxybenzene. The first of these is the better method.The flavonoids are polyphenolic compounds possessing a C6-C3-C6 skeleton ( Fig. 1) 1 , which occur widely in fruits and vegetables, and exhibit a broad spectrum of interesting biological activities against cancer, cardiovascular, and neurodegenerative diseases. 2 They are divided into several subgroups based on structural differences in their ring C involving its oxidation state. 3 The A and B-rings of naturally occurring flavonoids are usually functionalised by OH, OMe, isoprenyl, and glycosyl groups. The OH and glycosyl residues can be further functionalised by acyl, glycosyl or other flavonoid moieties. 3 They exert antioxidant and biological activities due to their aromatic moieties and the presence of oxygen functions. Luteolin (Fig. 2) is a polyphenolic flavonoid compound which has attracted considerable attention owing to its biological and pharmacological activities. 4-6 However, only a small amount of luteolin is available for biological studies because it is difficult to obtain. Among the published syntheses of luteolin, 7-9 none is attractive for large-scale synthesis due to drawbacks such as the use of expensive starting materials that are not easily accessible. Therefore, a simple and efficient synthetic method of luteolin is very desirable. We now report an efficient synthetic route for the preparation of luteolin (Scheme 1) based on our previous work. [10][11][12][13][14][15] Results and discussion

Novel extraction techniques and pharmaceutical activities of luteolin and its derivatives

“…Under the mild condition, this process yielded high demethylation. Acylation of 1, 3, 5‐trimethoxybenzene, condensation with 3, 4‐dimethoxybenzaldehyde or 3, 4‐dimethoxycinnamic acid, and 1, 3, 5‐trimethoxybenzene reaction have been reported as efficient methods for synthesis of luteolin and its derivatives (Zhang, Liu, Cui, Yang, & Yang, ). Luteolin and its derivatives have been proven to be potent cardiovascular protective agents due to many emerging evidences of metabolic syndromes treatment and management.…”

“…Under the mild condition, this process yielded high demethylation. Acylation of 1, 3, 5-trimethoxybenzene, condensation with 3, 4-dimethoxybenzaldehyde or 3, 4-dimethoxycinnamic acid, and 1, 3, 5-trimethoxybenzene reaction have been reported as efficient methods for synthesis of luteolin and its derivatives (Zhang, Liu, Cui, Yang, & Yang, 2014).…”

Modified Syntheses of the Dietary Flavonoid Luteolin

“…We have reported the synthesis of luteolin from 1,3,5-trimethoxybenzene using two routes in 47% and 32% yield, respectively. 26 As a continuation of our investigations on the synthesis of the bioactive natural flavonoids and their biological activities, 26,[27][28][29][30][31][32][33][34][35][36] we have carried out further studies and we now report the preparation of luteolin 1 using easily available starting materials, and by an improved procedure with satisfactory yields. JOURNAL OF CHEMICAL RESEARCH 2015 551 temperature apparatus, 1 H NMR spectral data were recorded on a Bruker Avance 400 NMR spectrometer or a Bruker DRX 500 NMR spectrometer, chemical shifts were reported in ppm against internal tetramethylsilane.…”

Hydnocarpin-Type Flavonolignans: Semisynthesis and Inhibitory Effects on Staphylococcus aureus Biofilm Formation

“…The solid residue obtained according to general procedures A and B, starting from compound 23 (0.2 g, 0.7 mmol), was purified by silica gel column chromatography (CHCl 3 /acetone/HCO 2 H, 80:20:1), affording nearly pure title compound, which was recrystallized from MeOH/H 2 O (9:1) to give pure 24 (55 mg, 29%) as a yellow, microcrystalline solid: mp 326–328 °C (reported mp 326 °C); 1 H NMR (DMSO- d 6 , 700.13 MHz) δ 6.187 (1H, d, J = 2.1 Hz, H-8), 6.441 (1H, d, J = 2.1 Hz, H-6), 6.664 (1H, s, H-3), 6.887 (1H, d, J = 8.3 Hz, H-13), 7.392 (1H, d, J = 2.3 Hz, H-10), 7.412 (1H, dd, J = 2.3, 8.3 Hz, H-14), 9.902, 9.391 (2H, br s, 11-OH, 12-OH), 10.814 (1H, br s, 7-OH), 12.969 (1H, s, 5-OH); 13 C NMR (DMSO- d 6 , 176.05 MHz) δ 93.90 (CH, C-8), 98.89 (CH, C-6), 102.94 (CH, C-3), 103.77 (C, C-4a), 113.44 (CH, C-10), 116.08 (CH, C-13), 119.06 (CH, C-14), 121.58 (C, C-9), 145.80 (C, C-11), 149.76 (C, C-12), 157.36 (C, C-8a), 161.55 (C, C-5), 163.96 (C, C-2), 164.19 (C, C-7), 181.72 (C, C-4); HRESIMS m / z 287.0553 [M + H] + (calcd for C 15 H 11 O 6 , 287.0550).…”