(4aR,5S,6S,6aR,9S,11aS,11bS,14R)-5,six,14-trihydroxy-4,4-dimethyl-8methylene-4,4a,five,six,9,ten,11,11a-octahydro-1H-6,11b-(epoxymethano)-6a,9methanocyclohepta[a]naphthalene-1,7(8H)-dione (7) To a remedy of six (eight.0 mg, 0.02 mmol) inside a mixture of MeOH (two mL) and CH2Cl2 (0.5 mL) was added 5 HCl aqueous option (0.five mL) at rt. The resulting mixture was stirred at rt for four h. The reaction mixture was then diluted with water and extracted with dichloromethane. The extract was washed with saturated NaHCO3 (aq.) remedy and brine, dried more than anhydrous Na2SO4, filtered, and evaporated to provide an oily residue. The residue was purified working with preparative TLC developed by 50 EtOAc in hexane to afford the preferred product 7 as a colorless amorphous gel (6.five mg, 89 ). []25D -56 (c 0.ten, CH2Cl2); HPLC purity 99.0 (tR = 16.02 min); 1H NMR (600 MHz, CDCl3/CD3OD = 5:1) 6.88 (d, 1H, J = 9.6 Hz), six.2-Bromonaphthalen-1-amine Order 21 (s, 1H), 5.87 (d, 1H, J = 10.2 Hz), five.63 (s, 1H), four.97 (s, 1H), 4.27 (m, 2H), 4.06 (dd, 1H, J = 1.2 Hz, ten.two Hz), three.96 (d, 1H, J = 8.4 Hz), 3.04 (d, 1H, J = 9.six Hz), two.52 (m, 1H), 2.10 (m, 2H), two.03 (d, 1H, J = eight.4 Hz), 1.62 (m, 1H), 1.48 (m, 1H), 1.39 (s,J Med Chem. Author manuscript; offered in PMC 2014 November 14.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDing et al.Page3H), 1.27 (s, 3H); 13C NMR (150 MHz, CDCl3/CD3OD = 5:1) 206.7, 197.3, 161.eight, 150.8, 126.8, 121.two, 97.9, 72.3, 72.two, 65.2, 61.4, 56.8, 50.0, 45.9, 42.7, 35.7, 29.8, 29.four, 23.9, 18.9; HRMS Calcd for C20H25O6: [M + H]+ 361.1646; discovered 361.1544. Synthesis of (3S,3aR,3a1R,6aR,7S,7aR,11aS,11bS,Z)-10-((dimethylamino)methylene)-7hydroxy-5,five,8,8-tetramethyl-15-methyleneoctahydro-1H-6a,11a-(epoxymethano)-3,3a1ethanophenanthro[1,10-de][1,3]dioxine-11,14(2H)-dione (eight) To a option of 2 (250 mg, 0.2-(3,4,5-Trimethoxyphenyl)acetonitrile custom synthesis 68 mmol) in acetone (10 mL) was added p-TsOH (20 mg) and two,2-dimethoxypropane (1.PMID:23563799 0 mL) at rt. The resulting mixture was stirred at rt for 2 h. The reaction mixture was then diluted with water and extracted with dichloromethane. The extract was washed with saturated NaHCO3 (aq.) answer and brine, dried over anhydrous Na2SO4, filtered, and evaporated to afford compound 3 as a colorless gel (263 mg, 95 ). To a solution of 3 (230 mg, 0.57 mmol) in DMF (four mL) was added DMF-DMA (136 mg, 1.14 mmol) at rt. The resulting mixture was refluxed at 110 for 36 h. The solvent was then removed beneath vacuum to provide a brown oily residue, which was further purified making use of preparative TLC created by 66 EtOAc in hexane to afford the preferred solution 8 as a brown gel (156 mg, 60 ). 1H NMR (600 MHz, CDCl3) 7.42 (s, 1H), 6.14 (s, 1H), five.55 (s, 1H), 5.20 (d, 1H, J = 12.0 Hz), four.87 (s, 1H), 4.31 (d, 1H, J = 10.2 Hz), four.04 (d, 1H, J = 10.two Hz), 3.87 (m, 1H), 3.07 (s, 6H), 3.04 (d, 1H, J = 9.6 Hz), two.47 (m, 3H), 1.97 (m, 2H), 1.66 (s, 3H), 1.62 (m, 1H), 1.56 (m, 2H), 1.34 (s, 3H), 1.23 (s, 3H), 1.00 (s, 3H); HRMS Calcd for C26H36NO6: [M + H]+ 458.2537; discovered 458.2541. Synthesis of (3S,3aR,3a1R,6aR,7S,7aR,11aS,11bS,Z)-7-hydroxy-10(hydroxymethylene)-5,five,eight,8-tetramethyl-15-methyleneoctahydro-1H-6a,11a(epoxymethano)-3,3a1-ethanophenanthro[1,10-de][1,3]dioxine-11,14(2H)-dione (9) To a resolution of 8 (200 mg, 0.43 mmol) in THF (five mL) was added 5 HCl aqueous answer (0.five mL) at rt. The resulting mixture was stirred at rt for 15 min. The reaction mixture was then diluted with water and extracted with dichloromethane. The extract was washed with saturated NaHCO3 (aq.) option and brine, dried over anhydro.
