Compound G16
(1S,4R,5bR,8S,10aS,11S,11aS,13R)-N-(Cyclohexylmethyl)-8,13-dihydroxy-1-methyl-9-methylene-2-oxo-2,4,5b,6,7,8,9,10,11,11a-decahydro-1H-1,4:8,10a-dimethanoazuleno[1,2-d]oxepine-11-carboxamide
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InChIKey HHOUAIRNMNUNOX-GAAVUFDMSA-N
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
In an oven-dried flask, G8 (128.4 mg, 0.37 mmol) and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (213.0 mg, 0.41 mmol) were dissolved in dichloromethane (4 mL). Diisopropylethylamine (200 µL, 1.15 mmol) was added, and the reaction was stirred at room temperature for 2 hours. After complete complexation by TLC, cyclohexanemethylamine (50 µL, 0.38 mmol) and additional diisopropylethylamine (50 µL, 0.29 mmol) were added, and the reaction was allowed to stir at room temperature for 16 hours. The reaction was quenched with water, extracted with ethyl acetate (3x), and concentrated. Purification by flash silica chromatography (1:1 to 1:2 hexanes/ethyl acetate) afforded pure G16 as a white solid (138.4 mg, 85% yield). 1H NMR (CDCl3, 500 MHz): δ 6.17 (t, J = 5.9 Hz, 1H), 5.77 (dt, J = 5.0, 2.4 Hz, 1H), 5.10 (t, J = 2.5 Hz, 1H), 4.97 (t, J = 2.0 Hz, 1H), 4.77 (t, J = 5.3 Hz, 1H), 4.24 (d, J = 5.3 Hz, 1H), 3.33 (dd, J = 5.9, 2.6 Hz, 1H), 3.14 (dt, J = 13.3, 6.6 Hz, 1H), 3.06 (dt, J = 13.3, 6.0 Hz, 1H), 2.82 - 2.74 (m, 1H), 2.51 (dt, J = 16.5, 2.9 Hz, 1H), 2.38 - 2.28 (m, 1H), 2.30 - 2.05 (br s, buried, 1H), 2.24 (d, J = 5.9 Hz, 1H), 1.97 - 1.86 (m, 1H), 1.78 - 1.62 (m, 7H), 1.58 - 1.52 (m, 1H), 1.51 (dd, J = 11.1, 2.7 Hz, 1H), 1.46 (ddp, J = 11.0, 7.0, 3.6 Hz, 1H), 1.34 (dd, J = 11.0, 2.7 Hz, 1H), 1.29 - 1.10 (m, 3H singlet buried, 7H), 1.00 - 0.85 (m, 2H). 13C NMR (CDCl3, 125 MHz): δ 177.9, 174.0, 153.9, 153.4, 113.1, 107.0, 79.2, 75.8, 74.3, 51.4, 49.5, 49.0, 48.7, 46.3, 45.7, 45.7, 39.1, 38.1, 37.5, 31.1 (2), 26.6, 26.0 (2), 18.9, 17.2. HRMS(ESI): m/z calc. for C26H36NO5 [M+H]+: 442.2593, found: 442.2585.
