Semisynthesis of Licochalcone E and Biological Evaluation as Vasorelaxant Agents

Highly Efficient Synthesis of Licochalcone E through Water-Accelerated [3,3]-Sigmatropic Rearrangement of Allyl Aryl Ether

“…The spectral data of this compound was nicely matched to the literature value. 4 (E)-2-Methoxy-4-(2-methylbut-2-enyloxy)benzaldehyde (6). 4-Hydroxy-2-methoxybenzaldehyde (1) (50 mg, 0.33 mmol), (E)-2-methyl-2-butenyl bromide (12) (74 mg, 0.49 mmol), anhydrous K 2 CO 3 (91 mg, 0.39 mmol) were dissolved in acetone (10 mL) and refluxed for 3 h. After completion of the reaction, K 2 CO 3 was filtered and the resulting solution was concentrated in vacuo and the residue was purified by silica gel flash column chromatography (EtOAc-Hexane = 1:7) to give an oil; yield: 67 mg (93%).…”

“…26 However, Our water-accelerated [3,3]-sigmatropic rearrangement conditions using EtOH/water co-solvent system provided the best yield of licochalcone E without deallylated by-product or regio-isomer within 24 h at 150 o C. The spectral data of licochalcone E were nicely matched to the previously reported results. 4,10,11,14,15 In summary, we developed a new synthetic pathway which enables sufficient supply of licochalcone E for biological tests (4 steps, overall 46% yield). This method could overcome the current situation of depending on multistep synthesis due to low isolated yield from natural resources.…”

“…4 They converted licochalcone A (5) to licochalcone E (4) with a good yield (77% by thermal reaction). But this method has also limitation (valuable licochalcone A itself was used as a starting material).…”

“…Among these, licochalcone E ( Fig. 1) gets drawing attentions due to its promising biological activities (antitumor, 9 vasorelaxant, 4 anti-inflammatory, 3 cytotoxic, 3 inhibitor of topoisomerase I, 4 protein tyrosine phosphatase 1B 4 etc). But because of the low isolated yield (5 mg from 1 Kg dried G. inflata) 7 and low yield producing current multi-step synthesis, growing needs were generated for developing new synthetic route.…”

“…1 They are reported to have various biological activities; antitumor, 2 anti-inflammatory, 3 vascular, 4 cytotoxic, 5 anti-proliferative, 6 inhibitor of topoisomerase I, 7 protein tyrosinase phosphatase 1B 8 etc. Among these, licochalcone E ( Fig.…”