Experimental Section for Compound 24 to 1 The cross-metathesis between 24 and freshmen distilled 2-methyl-2-butene (22°C, 24 h) is promoted by the Hoveyda-Grubbs II catalyst (0.2 equiv) and subsequence cleavage of the acetyl a group with DIBAL-H (5.0 equiv, dissolved in 1.0 mols of hexane) in a solvent of dichloromethane at -78°C for 30 minutes. This afforded anominine (1) in 83% yield over the two steps.Step h: O-Acetylated anominine 24a: To a solution of acetate 24 (11.2 mg, 0.0267 mmol) in fresh distilled 2-methyl-2-butene (700 µL) was added Hoveyda-Grubbs second generation catalyst 26 (3.0 mg, 0.0048 mmol) at 22°C. After removal of the solvent, the residue was subjected to flash column chromatography using CH2Cl2 as eluent to give O-Acetylated anominine 24a (11.3 mg, 95%) as a colorless oil. 24a: Rf = 0.34 (silica, EtOAc:petroleum ether 1:10); [α]26 D = -3.35 (c = 0.11 in CHCl3); IR(film): νmax = 3010, 2930, 2891, 2856, 1722, 1652, 1646, 1456, 1378, 1249, 1186, 1079, 1010, 834, 774cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.91 (br s, 1H), 7.64 (d, J = 7.8 Hz, 1 H), 7.33 (d, J = 8.0 Hz, 1 H), 7.20-7.15 (m, 1 H), 7.15-7.09 (m, 1 H), 6.96 (s, 1 H), 5.64 (s, 1 H), 5.10-5.00 (m, 1 H), 4.96 (s, 1 H), 4.87 (s, 1 H), 3.30-3.20 (m, 1 H), 3.18-3.07 (m, 2 H), 2.52-2.37 (m, 1 H), 2.28-2.11 (m, 3 H), 2.09 (s, 3 H), 1.90-1.83 (m, 3 H), 1.70 (s, 3 H), 1.62 (s, 3 H), 1.55-1.47 (m, 3 H), 1.39-1.24 (m, 3 H), 0.99 (s, 3 H), 0.84 (d, J = 6.5 Hz, 3 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 170.53, 148.65, 136.07, 131.01,127.77, 125.76, 121.99, 121.43, 119.34, 118.96, 117.04, 111.12, 108.09, 73.26, 47.64, 45.74, 41.28, 34.49, 33.64, 31.08, 29.57, 25.97, 25.88, 25.80, 23.76, 21.75, 21.69, 18.37, 17.76, 16.76 ppm; HRMS (m/z): [M + Na]+ calcd for C30H41NO2Na+ 470.3030; found 470.3033.Step i: (+)-Anominine: To a stirred solution of O-acetylated anominine 24a (11.3 mg, 0.0252 mmol) in CH2Cl2 (2 mL) was added DIBAL-H (120 µL, 1.0 M in hexanes, 0.12 mmol) at -78°C. The resulting mixture was stirred at that temperature for 30 min before it was quenched with saturated aq. NaHCO3 solution (5 mL). After extraction with EtOAc (5 × 5 mL), the combined organic phase was dried over anhydrous MgSO4, filtered, and concentrated under vacuum. The residue so obtained was purified by flash column chromatography with EtOAc/petroleum ether (1:5) to give (+)-anominine 1 (9.0 mg, 88%) as a white solid. 1: Rf = 0.21 (silica, EtOAc/petroleum ether 1:5); [α]26 D = +20.35 (c = 0.10 in MeOH); IR (film): νmax = 2962, 2922, 2850, 1714, 1644, 1457, 1377, 1261, 1096, 1013, 884, 802, 740 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.90 (br s, 1 H), 7.61 (d, J = 7.8 Hz, 1 H), 7.34 (d, J = 7.9 Hz, 1 H), 7.21-7.15 (m, 1 H), 7.15-7.08 (m, 1 H), 6.95 (s, 1 H), 5.23-5.15 (m, 1 H), 4.93 (s, 1 H), 4.82 (s, 1 H), 4.54 (s, 1 H), 3.29-3.20 (m, 1 H), 3.16-3.00 (m, 2 H), 2.53-2.40 (m, 1 H), 2.30-2.16 (m, 3 H), 2.15-2.07 (m, 1 H), 2.04-1.88 (m, 1 H), 1.73 (s, 3 H), 1.69 (s, 3 H), 1.67-1.62 (m, 1 H), 1.60-1.47 (m, 3 H), 1.41-1.31 (m, 2 H), 1.26 (m, 2 H), 1.03 (m, 3 H), 0.84 (d, J = 6.6 Hz, 3 H) ppm; 13C NMR (100 MHz, CDCl3): δ =149.08, 136.02, 131.43, 127.84, 125.96, 121.99, 121.39, 119.29, 118.71, 117.21, 111.19, 107.89, 70.11, 47.99, 45.97, 40.97, 34.52, 33.63, 31.24, 29.28, 28.86, 25.91, 25.52, 23.95, 21.50, 18.84, 17.97, 16.78 ppm; HRMS (m/z): [M + Na]+ calcd for C28H39NONa+ 428.2924; found 428.2916. (±)-1 was prepared in the same manner (m.p. 178-180°C, EtOAc/petroleum ether 1:1) for X-ray crystallographic analysis. |
|
|
