Oleanolic acid acetate

3-O-Acetyloleanolic acid (3AOA), an oleanolic acid derivative isolated from the seeds of Vigna sinensis K., induces in cancer and also exhibits anti-angiogenesis activity[1].

Ac2O (1.50 equivalents) was added to oleanic acid (2, 0 mmol, 1.00 eq.) in 10 mL of anhydrous pyridine in a 25 mL dry Schelenk flask.The reaction mixture was slowly warmed to room temperature (rt) overnight.The reaction mixture was washed several times with water and extracted with ethyl acetate.It was then dried over MgSO4.The filtrate was concentrated in vacuo to give pure Ac-oleanic acid for the next step (>99percent).Oleanolic acid (1, 80 mg) was dissolved in dry pyridine (4 mL) and treated with distilled acetic anhydride (2 mL). The mixture was stirred overnight at room temperature and monitored on TLC. After completion, the mixture was stirred with 5 mL of saturated NaHCOAcAcAcetylation of OA (5.0 g, 10.9 mmol) in dry pyridine (40 mL) with acetic anhydride (2.6 mL, 27.5 mmol), NEt1) Quqi acid 11mmol (5.00g) was dissolved in dry pyridine / dichloromethane (8mL, 7/1, v / v) added DMAP1.10mmol (0.13g) and acetic anhydride 16.5mmol (58.2mL ), the reaction was stirred for 12 hours at room temperature, the reaction solution was concentrated, and the residue was dissolved with 2NHCl, extracted twice with ethyl acetate, the combined organic layers; the organic layer was washed successively with water, saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated and the obtained residue was purified with a mixed solvent of ethanol and petroleum ether (VAcetylation of OA (5g; 10.95mmol) in dry pyridine (100mL) with acetic anhydride (2.6mL 27.4mmol), NEtA solution of OA (4.16 g, 11.12 mmol) and 30 ml of anhydrous pyridine was added to a dry 100 ml reaction flask, stirred well, cooled to 0 ° C in an ice bath, slowly added with acetic anhydride (10.52 ml, 111.2 mmol) DMAP (0.052 g, 0.42 mmol) was added and allowed to react overnight at room temperature during the reaction.After completion of the reaction, the reaction solution was poured into 200 ml of ice water and stirring was continued until the solid was completely precipitated, washed with dichloromethane (150 ml x 3), 5percent dilute hydrochloric acid 50 ml, distilled water (100 ml x 3), saturated brine (100 ml x 3) Extraction, the combined organic phase, anhydrous NaSO4 dry, standing, suction filtration, washing, evaporated solvent, dark yellow oil, vacuum drying at 50 overnight.Recrystallization from methanol-dichloromethane gave 4.9 g of compound 9 white needle-like crystals in 88percent yieldAcetylation of oleanolic acid (3.00 g, 6.58 mmol) in dry pyridine (40 mL) with acetic anhydride (1.20 mL, 12.7 mmol) in the presence of triethylamine (1.50 mL, 10.8 mmol) and catalytical amounts of DMAP for 1 day at 25 °C followed by usual aqueous workup and chromatography (SiOGeneral procedure: A solution of the triterpenoic acid 1-6 (2.56mmol) in dry DCM(100mL) was treated with acetic anhydride (1.045g, 10.24mmol), triethylamine (1.167g, 11.53mmol) and DMAP (31mg, 0.25mmol).The mixture was stirred at room temperature for one day, dilutedwith Et2O (500mL), and the mixture was subsequently washedwith aqueous HCl (0.1M, 1500mL), water (2500mL) and brine(1250mL), dried (MgSO4), and the filtratewas concentrated underdiminished pressure. The residue was subjected to column chromatography(silica gel, hexane/ethyl acetate, mixtures) to provideacetates 7-12 each as a colorless solid. Their spectroscopic datawere in full agreement with data from the literature.A solution of OA (3.0 g, 6.57 mmol) and DMAP(963.2 mg, 7.88 mmol) dissolved in anhydrous THF, stirring3 h at room temperature, then adding acetic anhydride (1.6 mL, 9.71 mmol) to mixture, stirring 2 h at room temperature.The solvent was evaporated under reduced pressureto remove THF. The residue was extracted with ethylacetate and water, washing to neutral with saturated NaClsolution. The organic layer was dried over anhydrous magnesiumsulfate. Filtration and evaporation of solvent atreduced pressure gave light yellow solid, which was purifiedby silica gel chromatography with a gradient elution of ethylacetate-petroleum ether (1:10, v/v) to yield a white solid(2.42 g, 73percent), m.p.259.5–261.5 °C; 1H-NMR (500 MHz, CDCl3)δ : 5.27 (s, 1H, H-12), 4.49 (t, J = 6.8 Hz, 1H, H-3), 2.81 (dd, J1 = 13.7 Hz, J2 = 4.2 Hz, 1H, H-18), 2.04 (s, 3H, CH3CO–), 1.13, 0.94, 0.93, 0.90, 0.87, 0.85, 0.75 (eachs, 3H); 13C-NMR (125 MHz, CDCl3) δ: 184.22, 171.01, 143.59, 122.54, 80.93, 55.30, 47.55, 46.54, 45.83, 41.54, 40.91, 39.29, 38.07, 37.68, 36.99, 33.79, 33.04, 32.53, 32.44, 30.64, 28.03, 27.66, 25.89, 23.57, 23.51, 23.38, 22.86, 21.26, 18.17, 17.14, 16.64, 15.36; IR (KBr) νmax2932, 2861 (CH), 1724(C=O), 1256 (C–O–C) cm-1.General procedure: A solution of the triterpenoic acid 1-4 (10.0 g, 22 mmol, 1.0 eq.) in acetic anhydride (160 mL) was stirred under reflux for 2 h. To the hot reaction mixture, acetic acid (20 mL) was slowly added. Stirring was continued for another 10 min, then water (40 mL) was slowlyadded, and the precipitate was filtered off. The precipitate was washed with water (4 x 50 mL), cold EtOH (20 mL) and dried underr educed pressure. The desired products were obtained as off-white solids that were pure enough (as checked by TLC, NMR, MS) for the next reaction steps. Analytical samples were obtained either by recrystallization or column chromatography.General procedure: To a well stirred and cooled at 0 °C solution of OA (1.0 equiv.) in dry CHGeneral procedure: A solution of the triterpenoic acid (10 g, 22 mmol, 1.0 eq.) inacetic anhydride (160 mL) was stirred at reflux for 2 h. To the hotreaction mixture acetic acid (20 mL) and water (40 mL) were slowlyadded. The precipitate was filtered off, washed with water(4 x 50 mL), cold EtOH (20 mL) and dried under reduced pressure.The products were obtained as white solids.

Molecular Weight:498.7
XLogP3:8.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:498.37091007
Monoisotopic Mass:498.37091007
Topological Polar Surface Area:63.6
Heavy Atom Count:36
Complexity:992
Defined Atom Stereocenter Count:8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes