# Regiosellective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin
## 2 Materials and Methods
Data for **14**: R\({}_{\rm f}\) = 0.66 (1:4 EtOAc/hexane); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.08 (d, \(J\) = 7.2 Hz, 3H), 1.59 (s, 3H), 1.60 (s, 6H), 1.68 (s, 3H), 1.94-2.12 (m, 10H), 2.13 (s, 3H), 2,14 (s, 3H), 2.18-2.24 (m, 1H), 2.32-2.41 (m, 1H), 5.04-5.13 (m, 3H), 5.22 (dd, \(J\) = 6.0, 1.6 Hz, 1H), 5.61 (d, \(J\) = 1.6 Hz, 1H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\))* \(\delta\) = 16.0 (16.0), 17.7, 19.1, 20.4 (20.9), 21.0 (21.3), 21.5, 25.7, 26.5 (26.6), 26.8, 29.3 (31.6), 31.3 (31.9), 39.7, 39.8 (39.9), 43.9 (46.0), 107.0 (108.9), 112.8 (113.4), 120.9 (121.1), 123.8 (124.3), 124.1 (124.4), 131.3 (131.4), 135.1 (135.3), 138.0 (138.5), 142.9 (153.1), 166.7 (167.8), 168.8 (169.0), 183.7 (185.1) ppm; IR v = 2962, 2922, 2855, 1765, 1614, 1448, 1367, 1275, 1190, 1119, 1096, 1006, 896, 846, 773, 734 cm\({}^{-1}\); HRMS (ESI) calcd. C\({}_{26}\)H\({}_{38}\)O\({}_{4}\)+H\({}^{*}\) for. 415.2848, found 415.2845. *: diastereomeric peaks are notified in parenthesis. **5-Methyl-4-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)-1,3-phenylene diacetate. ** To a stirred solution of diacetate **14** (130 mg, 0.31 mmol) in CH\({}_{2}\)Cl\({}_{2}\), DDQ (0.10 g, 0.44 mmol) was added. The mixture was stirred at 25 \({}^{\circ}\)C for 5 h and quenched with H\({}_{2}\)O. The mixture was then extracted with CH\({}_{2}\)Cl\({}_{2}\), dried over anhydrous Na\({}_{2}\)SO\({}_{4}\), filtered, and concentrated under reduced pressure. The crude product was purified by SiO\({}_{2}\) flash column chromatography (5-10% EtOAc/hexane eluent) to produce the aromatized diacetate (66 mg, 0.16 mmol) in 52% yield as a colorless oil. Data: R\({}_{\rm f}\) = 0.54 (EtOAc/hexane); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.58 (s, 3H), 1.59 (s, 3H), 1.67 (s, 3H), 1.73 (s, 3H), 1.92-2.10 (m, 8H), 2.26 (s, 3H), 2.28 (s, 3H), 2.29 (s, 3H), 3.22 (d, \(J\) = 6.4 Hz, 2H), 4.98 (t, \(J\) = 6.4 Hz, 1H), 5.04-5.13 (m, 2H), 6.70 (d, \(J\) = 2.4 Hz, 1H), 6.80 (d, \(J\) = 2.4 Hz, 1H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\)) \(\delta\) = 16.0, 16.2, 17.7, 19.8, 20.9, 21.1, 25.7, 25.8, 26.6, 26.7, 39.6, 39.7, 113.5, 120.9, 121.2, 124.0, 124.4, 129.7, 131.3, 135.1, 135.8, 139.2, 148.4, 149.1, 169.3, 169.3 ppm; IR v = 2919, 1769, 1617, 1588, 1480, 1441, 1367, 1289, 1195, 1119, 1046, 1017, 977, 902, 833, 772 cm\({}^{-1}\); HRMS (FAB) calcd. for. C\({}_{26}\)H\({}_{36}\)O\({}_{4}\)+H\({}^{+}\) 413.2692, found 413.2701. **Neogridin: 5-methyl-4-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)benzene-1,3-diol (2)**. To a stirred solution of the above aromatized diacetate (40 mg, 0.097 mmol) in MeOH (5 mL) at 0 \({}^{\circ}\)C a 50% aqueous solution of KOH (28 mg, 0.5 mmol) was added. The mixture was stirred at 25 \({}^{\circ}\)C for 10 min and quenched with 1 M HCl. The mixture was then extracted with EtOAc, dried over anhydrous Na\({}_{2}\)SO\({}_{4}\), filtered, and concentrated under reduced pressure. The crude product was purified by SiO\({}_{2}\) flash column chromatography (10-15% EtOAc/hexane) to produce neogridin **2** (31 mg, 0.094 mmol) in 97% yield as a colorless oil. Data for **2**: \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.58 (s, 3H), 1.59 (s, 3H), 1.67 (s, 3H), 1.79 (s, 3H), 1.93-2.14 (m, 8H), 2.23 (s, 3H), 3.29 (d, \(J\) = 6.8 Hz, 2H), 4.44 (s, 1H), 5.07 (dt, \(J_{\rm f}\) = 6.8, \(J_{\rm d}\) = 1.2 Hz, 2H), 5.08 (s, 1H), 5.15 (dt, \(J_{\rm f}\) = 6.8, \(J_{\rm d}\) = 1.2 Hz, 1H), 6.21 (d, \(J\) = 2.0 Hz, 1H), 6.26 (d, \(J\) = 2.0 Hz, 1H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\)) \(\delta\) = 16.0, 16.2, 17.7, 20.1, 20.1, 25.1, 25.7, 26.4,26.7, 39.7, 101.0, 109.6, 117.9, 122.0, 123.7, 124.4, 131.3, 135.5, 137.8, 138.5, 154.2, 155.5 ppm; IR \(\
u\) = 3396 (br s), 2965, 2919, 2854, 1596, 1508, 1465, 1449, 1377, 1329, 1279, 1201, 1167, 1138, 1048, 980, 831, 791, 756 cm\({}^{-1}\); HRMS (FAB)calcd. for C\({}_{22}\)H\({}_{32}\)O\({}_{2}\) 328.2402, found 328.2401.