List of supplementary data
Fig. S1 Synthetic pathway ofGAOBn
Fig. S2 Preliminary screening of GAOBn at concentration of 20 μg/ml against BT474,
KATO-3, Hep-G2, CHAGO, SW620 comparison with GA
Supplementary data
Synthesis of 3,4,5-tribenzyloxybenzoic acid (GAOBn) as a potent lung anticancer agent
The synthesis of GAOBn is shown in Fig. S1.
Synthesis of methyl 3,4,5-trihydroxybenzoate (1): 4.99 g (29.3 mmol) of gallic acid was dissolved in 30 ml of methanol. 1.6 ml of sulfuric acid 37% (29.0 mmol) was added and refluxed for 6 h at 60°C. The reaction solution was then evaporated. 200 ml of water was added to the residue and extracted with ethyl acetate (3×40 ml). The organic layer was washed with brine, dried on sodium sulfate and evaporated. Yield: 99%. 1H NMR (400 MHz, D2O): 6.97 (s, 2H), 3.66 (s, 3H). IR (KBr, cm-1): 3455, 3366, 1692, and 1618.
Synthesis of methyl 3,4,5-tribenzyloxybenzoate (2): 5.00 g (27.2 mmol) of (1) was dissolved in 35 ml of dimethylformamide. Then, 11.27 g (81.5 mmol) of potassium carbonate and 9.5 ml (82.4 mmol) of benzyl chloride were added in the solution. The mixture was stirred at 60°C under N2 atmosphere for 24 h. The resulting mixture solution was filtered. The filtrate was taken up in 350 ml of water and extracted with dichloromethane (3x50 ml). The organic layer was washed with brine, dried on sodium sulfate and evaporated. Yield: 60%. 1H NMR (400 MHz, CDCl3): 7.44-7.33 (m, 17H), 5.13 (s, 4H), 5.11 (s, 2H), 3.88 (s, 3H). IR (KBr, cm-1): 3412, 1713, and 1587.
Synthesis of 3,4,5-tribenzyloxybenzoic acid, GAOBn (3): 7.00 g (15.4 mmol) of (2) was dissolved in 125 ml of methanol. 3.10 g (77.5 mmol) of sodium hydroxide was added. The mixture solution was refluxed at 60°C for 24 h. 125 ml of water was added and acidified by 37% hydrochloric acid. The precipitated product was filtered and washed with water. Yield: 96%. 1H NMR (400 MHz, CDCl3): 7.46-7.31 (m, 17H), 5.14 (s, 4H), 5.13 (s, 2H). IR (KBr, cm-1): 1686 and 1593. MALDI-TOF (m/z) for C28H24O5: calc. 440.16, found 440.71.
Figure S1 Synthetic pathway of GAOBn
Figure S2 Preliminary screening of GAOBn at concentration of 20 μg/ml against BT474, KATO-3, Hep-G2, CHAGO, SW620 comparison with GA