ࡱ> tvsy9 RxXbjbj6Pl|||||||ZZZ8K]n___\\\\\\\$S_ saR\]|_____\0||]000_j ||\0_\0607nS||Wb u´ԱZ% T W|]0K]Ua_0"aW0||||Supporting Information Title: The First Total Synthesis of ()-Linderol A, a Tricyclic Hexahydrodibenzofuran Constituent of Lindera Umbellata Bark, with Potent Inhibitory Activity on Melanin Biosynthesis of Cultured B-16 Melanoma Cells Authors: Masayuki Yamashita, Nobukazu Ohta, Ikuo Kawasaki, and Shunsaku Ohta* Address: Kyoto Pharmaceutical University, Misasagi-Nakauchicho 5, Yamashinaku, Kyoto 607-8414, Japan. E-mail: sohta@mb.kyoto-phu.ac.jp Ethyl 5,7-Dimethoxycoumarin-3-carboxylate (5) Yield; 97.0 %. Pale yellow needles. mp, 164.7 ~ 166.9C (Benzene). 1H-NMR (400 MHz, CDCl3) (: 1.40 (t, 3H, J = 7.0 Hz, -OCH2CH3), 3.88, 3.93 (each s, each 3H, ArOCH3), 4.39 (q, 2H, J = 7.1 Hz, -OCH2CH3), 6.27, 6.40 (each d, each 1H, J = 2.0 Hz, Ar-H), 8.82 (d, 1H, J = 0.5 Hz, ArCH=). 13C-NMR (100 MHz, CDCl3) (: 14.3, 56.0, 56.1, 61.4, 92.5, 95.0, 103.5, 111.6, 144.5, 157.4, 158.3, 158.4, 163.6, 166.3. IR (CHCl3) : 1751, 1698, 1613, 1600, 1562, 1466, 1370, 1154, 1113 cm-1. LR-EIMS : 278 (M+, 89.0), 233 (100), 206 (83.8), 178 (39.2). HR-EIMS m/z : Calcd for C14H14O6, 278.0790. Found, 278.0797 (M+). Anal. Calcd for C14H14O6 : C, 60.43; H, 5.07. Found : C, 60.33; H, 5.04. Ethyl (3aR*,8bS*)-3-Hydroxy-6,8-dimethoxy-3a,8b-dihydro-1H-cyclopenta[b]benzofuran-2-carboxy- late (6) Yield; 78.8 %. Colorless needles. mp, 148.2 ~ 150.2C (EtOH). 1H-NMR (400 MHz, CDCl3) (: 1.29 (t, 3H, J = 7.1 Hz, - OCH2CH3), 2.76 (dt, 1H, J = 15.2, 1.8 Hz, ArCHCH2-), 2.90 (dd, 1H, J = 7.9, 15.2 Hz, ArCHCH2-), 3.75, 3.81 (each s, each 3H, ArOCH3), 4.02 (dt, 1H, J = 1.7, 8.2 Hz, ArCH-), 4.21 (q, 2H, J = 7.1 Hz, - OCH2CH3), 5.65 (dd, 1H, J = 1.5, 8.8 Hz, ArOCH-), 6.03, 6.10 (each d, each 1H, J = 2.0 Hz, Ar-H), 10.02 (s, 1H, -OH). 13C-NMR (100 MHz, CDCl3) (: 14.3, 32.4, 38.4, 55.3, 55.6, 60.5, 88.5, 88.7, 91.7, 103.1, 109.0, 156.8, 160.2, 162.1, 167.7, 169.5. IR (CHCl3) : 3500-3000, 2927, 1668, 1623, 1599, 1498, 1233, 1142, 1090 cm-1. LR-EIMS : 306 (M+, 31.7), 260 (36.0), 178 (100.0), 135 (15.8). HR-EIMS m/z : Calcd for C16H18O6, 306.1103. Found, 306.1092 (M+). Anal. Calcd for C16H18O6 : C, 62.74; H, 5.92. Found : C, 62.64; H, 5.85. Ethyl (3aR*,8bS*)-6,8-Dimethoxy-3-oxo-3a,8b-dihydro-3H-cyclopenta[b]benzofuran-2-carboxylate (7) Yield; 78.9 %. Pale yellow-green powders. mp, 106.5 ~ 109.6C (AcOEtpetroleum ether). 1H-NMR (400 MHz, CDCl3) (: 1.32 (t, 3H, J = 7.1 Hz, - OCH2CH3), 3.74, 3.84 (each s, each 3H, ArOCH3), 4.26, 4.30 (each dq, each 1H, J = 10.8, 7.1 Hz, -OCH2CH3), 4.60 (dd, 1H, J = 2.9, 7.0 Hz, ArCH-), 5.09 (d, 1H, J = 7.0 Hz, ArOCH-), 6.02, 6.06 (each d, each 1H, J = 2.0 Hz, Ar-H), 8.56 (d, 1H, J = 2.9 Hz, CH=C-). 13C-NMR (100 MHz, CDCl3) (: 14.1, 44.6, 55.4, 55.6, 61.2, 83.8, 89.0, 91.9, 103.7, 135.6, 156.7, 161.42, 163.1, 170.3, 197.2. IR (CHCl3) : 1753, 1699, 1614, 1605, 1582, 1456, 1369, 1228, 1154 cm-1. LR-EIMS : 304 (M+, 74.2), 260 (35.9), 191 (77.4), 178 (100.0). HR-EIMS m/z : Calcd for C16H16O6, 304.0947. Found, 304.0945 (M+). Anal. Calcd for C16H16O6 : C, 63.15; H, 5.30. Found : C, 62.85; H, 5.28. Ethyl (1R*, 3aR*,8bS*)-3-Hydroxy-6,8-dimethoxy-1-(1-methylethyl)-3a,8b-dihydro-1H-cyclopenta- [b]benzofuran-2-carboxylate (8) Yield; 65.5 %. Colorless needles. mp, 124.0 ~ 124.7C (AcOEtn-hexane). 1H-NMR (400 MHz, CDCl3) (: 0.73, 1.13 (each d, each 3H, J = 6.8 Hz, (CH3)2CH-), 1.28 (t, 3H, J = 7.1 Hz, -OCH2CH3), 2.13 (d7, 1H, J = 3.3, 7.0 Hz, (CH3)2CH-), 3.22 (ddd, 1H, J = 1.1, 1.8, 3.3 Hz, (CH3)2CHCH-), 3.70 (dd, 1H, J = 1.1, 8.1 Hz, ArCH-), 3.74, 3.79 (each s, each 3H, ArOCH3), 4.19, 4.25 (each dq, each 1H, J = 10.8, 7.1 Hz, -OCH2CH3), 5.59 (dd, 1H, J = 1.8, 8.2 Hz, ArOCH-), 6.01, 6.09 (each d, each 1H, J = 2.0 Hz, Ar-H), 10.24 (s, 1H, -OH). 13C-NMR (100 MHz, CDCl3) (: 14.2, 16.6, 20.9, 30.1, 41.1, 51.2, 55.1, 55.5, 60.4, 88.0, 88.4, 91.7, 106.0, 108.6, 156.9, 160.1, 161.9, 168.9, 169.8. IR (CHCl3) : 3500-3000, 2932, 1706, 1659, 1620, 1600, 1496, 1140, 1088 cm-1. LR-EIMS : 348 (M+, 39.2), 302 (24.9), 259 (23.5), 207 (44.7), 178 (100.0). HR-EIMS m/z : Calcd for C19H24O6, 348.1573. Found, 348.1580 (M+). Anal. Calcd for C19H24O6 : C, 65.50; H, 6.94. Found : C, 65.39; H, 6.92. (1R*,3aR*,8bS*)-6,8-Dimethoxy-1-(1-methylethyl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzo- furan-3-one (9) Yield; 98.2 %. Colorless needles. mp, 106.5 ~ 108.3C (AcOEtn-hexane). 1H-NMR (400 MHz, CDCl3) (:0.94, 0.96 (each d, each 3H, J = 6.8 Hz, (CH3)2CH-), 1.87 (d7, 1H, J = 5.1, 6.8 Hz, (CH3)2CH-), 2.20 (ddq, 1H, J = 18.7, 3.8, 1.5 Hz, -CH2CO-), 2.32 (dd, 1H, J = 18.7, 9.2 Hz, -CH2CO-), 2.57 (m, 1H, (CH3)2CHCH-), 3.75, 3.80 (each s, each 3H, ArOCH3), 3.96 (dd, 1H, J = 1.6, 9.2 Hz, ArCH-), 4.77 (dt, 1H, J = 9.2, 0.7 Hz, ArOCH-), 6.03, 6.06 (each d, each 1H, J = 2.0 Hz, Ar-H). 13C-NMR (100 MHz, CDCl3) (: 18.9, 19.9, 32.2, 38.7, 44.3, 44.8, 55.3, 55.6, 84.9, 88.2, 92.1, 107.8, 156.9, 160.7, 162.1, 214.7. IR (CHCl3) : 2946, 1745, 1620, 1598, 1497, 1461, 1086 cm-1. LR-EIMS : 276 (M+, 23.2), 220 (33.2), 178 (100.0), 163 (18.1). HR-EIMS m/z : Calcd for C16H20O4, 276.1361. Found, 276.1360 (M+). Anal. Calcd for C16H20O4 : C, 69.54; H, 7.30. Found : C, 69.52; H, 7.42. Ethyl (1R*,4aR*,9bS*)-4-Hydroxy-7,9-dimethoxy-1-(1-methylethyl)-1,2,4a,9b-tetrahydrodibenzo- furan-3-carboxylate (10) Yield; 85.8 %. Colorless needles. mp, 102.0 ~ 102.9C (AcOEtpetroleum ether). 1H-NMR (400 MHz, CDCl3) (: 0.947 (d, 3H, J = 7.7 Hz, (CH3)2CH-), 0.949 (d, 3H, J = 6.6 Hz, (CH3)2CH-), 1.33 (t, 3H, J = 7.1 Hz, - OCH2CH3), 1.68 (ddd, 1H, J = 3.9, 4.5, 9.7 Hz, (CH3)2CHCH-), 1.81 (d7, 1H, J = 4.6, 6.8 Hz, (CH3)2CH-), 2.05 (dd, 1H, J = 9.5, 16.1 Hz, -CH2C=C), 2.32 (dd, 1H, J = 3.9, 16.1 Hz, -CH2C=C), 3.40 (dd, 1H, J = 7.5, 9.7 Hz, ArCH), 3.76, 3.78 (each s, each 3H, Ar-OCH3), 4.24, 4.28 (each dq, each 1H, J = 10.8, 7.1 Hz, - OCH2CH3), 4.96 (d, 1H, J = 7.5 Hz, ArOCH-), 6.04, 6.15 (each d, each 1H, J = 2.0 Hz, Ar-H), 12.00 (s, 1H, -OH). 13C-NMR (100 MHz, CDCl3) (: 14.2, 17.1, 20.9, 21.8, 27.2, 42.2, 42.7, 55.1, 55.5, 60.9, 81.2, 89.1, 91.6, 101.5, 109.2, 157.3, 160.9, 161.7, 164.1, 172.1. IR (CHCl3) : 3500-3000, 2941, 1738, 1657, 1617, 1590, 1496, 1460, 1138, 1093 cm-1. LR-EIMS : 362 (M+, 18.9), 273 (10.0), 178 (60.5), 154 (100.0). HR-EIMS m/z : Calcd for C20H26O6, 362.1729. Found, 362.1716 (M+). Anal. Calcd for C20H26O6 : C, 66.28; H, 7.23. Found : C, 66.07; H, 7.16. Ethyl (1R*,4aR*,9bS*)-7,9-Dimethoxy-4-methoxymethoxy-1-(1-methylethyl)-1,2,4a,9b-tetrahydro- dibenzofuran-3-carboxylate (11) Yield; 84.0 %. Colorless oil. 1H-NMR (400 MHz, CDCl3) (: 0.93 (d, 3H, J = 7.3 Hz, (CH3)2CH-), 0.94 (d, 3H, J = 7.0 Hz, (CH3)2CH-), 1.32 (t, 3H, J = 7.1 Hz, - OCH2CH3), 1.64 (tt, 1H, J = 4.0, 10.4 Hz, (CH3)2CHCH-), 1.83 (d7, 1H, J = 4.0, 6.8 Hz, (CH3)2CH-), 2.13 (ddd, 1H, J = 1.3, 10.3, 17.0 Hz, -CH2C=C), 2.44 (dd, 1H, J = 3.8, 17.0 Hz, -CH2C=C), 3.31 (dd, 1H, J = 7.1, 10.4 Hz, ArCH-), 3.53 (s, 3H, -OCH2OCH3), 3.76, 3.77 (each s, each 3H, ArOCH3), 4.24 (q, 2H, J = 7.1 Hz, -OCH2CH3), 5.02, 5.34 (each d, each 1H, J = 6.6 Hz, -OCH2-), 5.16 (d, 1H, J = 7.0 Hz, ArOCH-), 6.04, 6.09 (each d, each 1H, J = 2.0 Hz, Ar-H). 13C-NMR (100 MHz, CDCl3) (: 14.3, 16.5, 21.8, 24.5, 27.0, 41.7, 42.9, 55.1, 55.5, 56.8, 60.5, 80.4, 89.1, 91.5, 95.4, 109.5, 115.5, 152.6, 157.2, 160.7, 161.6, 167.3. IR (CHCl3) : 2930, 1702, 1616, 1595, 1494, 1460, 1138, 1089 cm-1. LR-EIMS : 406 (M+, 30.3), 207 (25.4), 178 (100.0), 154 (38.0). HR-EIMS m/z : Calcd for C22H30O7, 406.1991. Found, 406.1974 (M+). (1R*,5aR*,9bS*)-7,9-Dimethoxy-1-(1-methylethyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran-4- one (12) Yield; 72.2 %. Colorless needles. mp, 78.2 ~ 80.4C (AcOEt-petroleum ether). 1H-NMR (400 MHz, CDCl3) (: 0.95, 1.02 (each d, each 3H, J = 6.6 Hz, (CH3)2CH-), 1.62-1.68 (m, 1H, (CH3)2CHCH-), 1.71-1.84 (m, 2H, -CH2CH2CO-), 1.85-1.93 (m, 1H, (CH3)2CH-), 2.43-2.58 (m, 2H, -CH2CO-), 3.77, 3.78 (each s, each 3H, ArOCH3), 3.84 (dd, 1H, J = 6.2, 8.6 Hz, ArCH-), 4.70 (dd, 1H, J = 0.6, 8.4 Hz, ArOCH-), 6.05, 6.14 (each d, each 1H, J = 2.0 Hz, Ar-H). 13C-NMR (100 MHz, CDCl3) (: 18.5, 21.0, 21.6, 28.0, 35.5, 43.1, 45.8, 55.2, 55.5, 85.8, 88.8, 92.1, 109.1, 156.7, 161.2, 161.9, 208.2. IR (CHCl3) : 2936, 1715, 1619, 1595, 1495, 1450, 1136, 1091 cm-1. LR-EIMS : 290 (M+, 27.0) , 220 (39.7), 178 (100.0), 163 (19.7). HR-EIMS m/z : Calcd for C17H22O4, 290.1518. Found, 290.1528 (M+).00Anal. Calcd for C17H22O4 : C, 70.32; H, 7.64. Found : C, 70.12; H, 7.61. (5aR*,9R*,9aS*)-1,3-Dimethoxy-9-(1-methylethyl)-6-methylidene-5a,6,7,8,9,9a-hexahydrodibenzo- furan (13) Yield; 97.2 %. Colorless needles. mp, 73.4 ~ 74.7C (AcOEt-n-hexane). 1H-NMR (400 MHz, CDCl3) (: 0.872 (d, 3H, J = 6.6 Hz, (CH3)2CH-), 0.874 (d, 3H, J = 7.1 Hz, (CH3)2CH-), 1.12 (ddt, 1H, J = 4.2, 13.0, 11.4 Hz, (CH3)2CHCHCH2-), 1.32 (ddt, 1H, J = 9.5, 11.4, 3.3 Hz, (CH3)2CHCH-), 1.69 (ddt, 1H, J = 3.1, 13.0, 4.6 Hz, (CH3)2CHCHCH2-), 1.92 (d7, 1H, J = 4.0, 6.8 Hz, (CH3)2CH-), 2.320(dddt, 1H, J = 4.6, 11.4, 13.9, 1.8 Hz, -CH2C=CH2), 2.42 (dt, 1H, J = 14.1, 4.4 Hz, -CH2C=CH2), 3.09 (dd, 1H, J = 6.2, 9.5 Hz, ArCH-), 3.76, 3.77 (each s, each 3H, ArOCH3), 4.78 (d, 1H, J = 6.0 Hz, ArOCH-), 5.12, 5.15 (each t, each 1H, J = 1.8 Hz, -C=CH2), 6.04, 6.11 (each d, each 1H, J = 2.0 Hz, Ar-H). 13C-NMR (100 MHz, CDCl3) (: 16.3, 21.8, 22.8, 27.3, 30.2, 43.9, 46.0, 55.2, 55.5, 88.8, 89.2, 91.4, 113.2, 116.2, 144.2, 156.6, 161.2, 161.3. IR (CHCl3) : 2920, 1613, 1590, 1140, 1106 cm-1. LR-EIMS : 288 (M+, 48.8), 218 (100.0), 205 (28.0), 167 (29.8), 149 (45.7). HR-EIMS m/z : Calcd for C18H24O3, 288.1725. Found, 288.1730 (M+). Anal. Calcd for C18H24O3 : C, 74.97; H, 8.39. Found : C, 74.71; H, 8.35. (1R*,4S*,4aR*,9bS*)-4-Hydroxymethyl-7,9-dimethoxy-1-(1-methylethyl)-1,2,3,4,4a,9b-hexahydro- dibenzofuran-4-ol (14) Yield; 100.0 %. Colorless oil. 1H-NMR (400 MHz, CDCl3) ((: 0.83 (d, 3H, J = 7.1 Hz, (CH3)2CH-), 0.91 (d, 3H, J = 6.8 Hz, (CH3)2CH-), 1.09-1.16 (m, 1H, (CH3)2CHCH-), 1.40-1.58 (m, 2H, (CH3)2CHCHCH2-), 1.43 (s, 1H, -CH2OH), 1.72 (ddd, 1H, J = 3.2, 4.8, 13.2 Hz, -CH2COH ), 1.95 (d7, 1H, J = 2.8, 6.8 Hz, (CH3)2CH-), 2.00-2.06 (m, 1H, -CH2COH), 2.34 (s, 1H, 4-OH), 3.13 (dd, 1H, J = 5.6, 11.2 Hz, ArCH-), 3.56 (dd, 1H, J = 6.0, 10.8 Hz, -CH2OH), 3.76, 3.77 (each s, each 3H, ArOCH3), 3.93 (dd, 1H, J = 4.8, 11.2 Hz, -CH2OH), 4.25 (dd, 1H, J = 1.6, 5.6 Hz, ArOCH-), 6.05, 6.11 (each d, each 1H, J = 2.0 Hz, Ar-H). 13C-NMR (100 MHz, CDCl3) (: 15.5, 16.6, 21.8, 27.1, 30.2, 40.2, 46.9, 55.2, 55.5, 68.7, 71.2, 87.7, 89.5, 91.8, 113.7, 156.7, 160.7, 161.1. IR (CHCl3) : 3600-3100, 2855, 1615, 1598, 1137 cm-1. LR-EIMS : 322 (M+, 16.6), 291 (100.0), 217 (9.3), 178 (41.4). HR-EIMS m/z : Calcd for C18H26O5, 322.1780. Found, 322.1785 (M+). (1R*, 4S*, 4aR*,9bS*)-7,9-Dimethoxy-1-(1-methylethyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran-4- spiro-4-dioxoran-2-one (15) Yield; 97.2 %. Colorless needles. mp, 149.0 ~ 150.9C (AcOEt-petroleum ether). 1H-NMR (400 MHz, CDCl3) (: 0.84, (d, 3H, J = 7.0 Hz, (CH3)2CH-), 0.90 (d, 3H, J = 6.8 Hz, (CH3)2CH-), 1.16 (ddt, 1H, J = 11.0, 12.5, 3.1 Hz, (CH3)2CHCH-), 1.46 (dq, 1H, J = 2.8, 13.2 Hz, (CH3)2CHCHCH2-), 1.57 (ddd, 1H, J = 3.7, 7.1, 13.7 Hz, (CH3)2CHCHCH2-), 1.81 (dt, 1H, J = 3.7, 14.1 Hz, -CH2CH2CH-), 2.00 (d7, 1H, J = 2.9, 6.8 Hz, (CH3)2CH-), 2.12 (ddd, 1H, J = 3.1, 4.9, 14.1 Hz, -CH2CH2CH-), 3.18 (dd, 1H, J = 5.5, 11.0 Hz, ArCH-), 3.77, 3.78 (each s, each 3H, ArOCH3), 4.34 (dd, 1H, J = 1.7, 5.5 Hz, ArOCH-), 4.19, 4.73 (each d, each 1H, J = 8.8 Hz, O=COCH2-), 6.08, 6.09 (each d, each 1H, J = 2.0 Hz, Ar-H). 13C-NMR (100 MHz, CDCl3) (: 15.4, 17.5, 21.7, 27.0, 32.0, 40.7, 46.1, 55.3, 55.5, 72.2, 81.2, 85.5, 89.4, 92.3, 113.0, 154.2, 156.7, 159.8, 161.4. IR (CHCl3) : 2936, 1798, 1619, 1492, 1170, 1135, 1108 cm-1. LR-EIMS : 348 (M+, 100), 263 (40.6), 191 (52.6). HR-EIMS m/z : Calcd for C19H24O6, 348.1573. Found, 348.1579 (M+). Anal. Calcd for C19H24O6 : C, 65.50; H, 6.94. Found : C, 65.26; H, 6.94. (1R*, 4S*, 4aR*,9bS*)-6-Acetyl-7,9-dimethoxy-1-(1-methylethyl)-1,2,3,4,4a,9b-hexahydrodibenzo- furan-4-spiro-4-dioxoran-2-one (16) Yield; 75.9 %. Colorless needles. mp, 174.5 ~ 177.0C (AcOEt-petroleum ether). 1H-NMR (400 MHz, CDCl3) (: 0.84 (d, 3H, J = 7.0 Hz, (CH3)2CH-), 0.90 (d, 3H, J = 6.8 Hz, (CH3)2CH-), 1.20 (ddt, 1H, J = 11.5, 12.1, 2.9 Hz, (CH3)2CHCH-), 1.46 (dq, 1H, J = 13.4, 2.9 Hz, (CH3)2CHCHCH2-), 1.55-1.62 (m, 1H, (CH3)2CHCHCH2-), 1.87 (dt, 1H, J = 3.5, 14.1 Hz, -CH2CO-), 1.92 (d7, 1H, J = 2.9, 6.8 Hz, (CH3)2CH-), 2.12 (ddd, 1H, J = 2.9, 5.0, 14.3 Hz, -CH2CO-), 2.49 (s, 3H, COCH3), 3.19 (dd, 1H, J = 5.7, 11.2 Hz, ArCH-), 3.86, 3.88 (each s, each 3H, ArOCH3), 4.38 (dd, 1H, J = 1.7, 5.7 Hz, ArOCH-), 4.21, 4.76 (each d, each 1H, J = 9.0 Hz, -OCH2-), 6.07 (s, 1H, Ar-H). 13C-NMR (100 MHz, CDCl3) (: 15.3, 17.5, 21.6, 27.1, 31.9, 32.5, 40.0, 45.8, 55.4, 56.1, 72.2, 80.9, 86.0, 89.0, 109.1, 113.8, 154.1, 158.3, 159.0, 160.2, 197.3. IR (CHCl3) : 2932, 1796, 1667, 1604, 1095, 1055 cm-1. LR-EIMS : 390 (M+, 100.0), 375 (39.2), 305 (15.2), 233 (46.2), 221 (63.1), 205 (37.7). HR-EIMS m/z : Calcd for C21H26O7, 390.1678. Found, 390.1681 (M+). Anal. Calcd for C21H26O7 : C, 64.60; H, 6.71. Found : C, 64.40; H, 6.72. (1R*, 4S*, 4aR*,9bS*)-6-Acetyl-7-hydroxy-9-methoxy-1-(1-methylethyl)-1,2,3,4,4a,9b-hexahydrodi- benzofuran-4-spiro-4-dioxoran-2-one (17) Yield;100.0 %. Colorless needles. mp, 198.5 ~ 201.7C (AcOEt-petroleum ether). 1H-NMR (400 MHz, CDCl3) (: 0.86 (d, 3H, J = 7.1 Hz, (CH3)2CH-), 0.90 (d, 3H, J = 6.8 Hz, (CH3)2CH-), 1.18 (ddt, 1H, J = 11.0, 12.3, 3.1 Hz, (CH3)2CHCH-), 1.49 (dq, 1H, J = 2.9, 13.0 Hz, (CH3)2CH CH CH2-), 1.62 (dq, 1H, J = 13.7, 3.6 Hz, (CH3)2CH CH CH2-), 1.83 (ddd, 1H, J = 3.7, 13.0, 14.1 Hz, -CH2CO-), 1.92 (d7, 1H, J = 2.9, 7.0 Hz, (CH3)2CH-), 2.18 (ddd, J = 1.7, 3.3, 14.3 Hz, -CH2CO-), 2.56 (s, 3H, COCH3), 3.22 (dd, 1H, J = 5.9, 11.0 Hz, ArCH-), 3.83 (s, 3H, ArOCH3), 4.48 (dd, 1H, J = 1.7, 5.7 Hz, ArOCH-), 4.25, 4.71 (each d, each 1H, J = 8.8 Hz, -OCH2-), 6.09 (s, 1H, Ar-H), 13.15 (s, 1H, -OH). 13C-NMR (100 MHz, CDCl3) (: 15.3, 17.4, 21.6, 27.1, 31.1, 32.0, 39.9, 46.2, 55.6, 72.0, 80.8, 86.6, 93.6, 102.8, 112.1, 153.8, 160.4, 161.8, 165.6, 201.0. IR (CHCl3) : 3200-2500, 2932, 1797, 1627, 1599, 1054 cm-1. LR-EIMS : 376 (M+, 100.0), 291 (22.8), 244 (19.3), 219 (36.1), 207 (25.4), 191 (28.6). HR-EIMS m/z : Calcd for C20H24O7, 376.1522. Found, 376.1525 (M+). Anal. Calcd for C20H24O7 : C, 63.82; H, 6.43. Found : C, 63.73; H, 6.51. (5aR*, 6S*, 9R*,9aS*)-4-Acetyl-3,6-dihydroxy-6-hydroxymethyl-1-methoxy-9-(1-methylethyl)-5a,6,7, 8,9,9a-hexahydrodibenzofuran (18) Yield; 85.9 %. Colorless powders. mp, 175.9 ~ 177.4C (AcOEt-petroleum ether). 1H-NMR (400 MHz, CDCl3) (: 0.85 (d, 3H, J = 7.0 Hz, (CH3)2CH-), 0.91 (d, 3H, J = 6.8 Hz, (CH3)2CH-), 1.12 (tt, 1H, J = 11.2, 3.1 Hz, (CH3)2CHCH-), 1.37-1.57 (m, 3H, -CH2CH2COH and 6-OH), 1.76-1.92 (m, 3H, -CH2COH and (CH3)2CH-), 2.34 (br, 1H, -CH2OH), 2.59 (s, 3H, COCH3), 3.14 (dd, 1H, J = 5.7, 11.2 Hz, ArCH-), 3.82 (s, 3H, ArOCH3), 3.62, 3.95 (each d, each 1H, J = 10.8 Hz, -CH2OH), 4.35 (dd, 1H, J = 1.5, 5.7 Hz, ArOCH-), 6.04 (s, 1H, Ar-H), 13.16 (s, 1H, ArOH). 13C-NMR (100 MHz, CDCl3) (: 15.4, 16.5, 21.7, 27.2, 30.3, 31.1, 39.4, 47.0, 55.5, 68.5, 70.9, 88.4, 92.7, 102.9, 112.8, 161.7, 161.8, 165.1, 201.5. IR (CHCl3) : 3700-3200, 2923, 1627, 1597, 1069 cm-1. LR-EIMS : 350 (M+, 22.6), 319 (100.0), 207 (36.4), 191 (21.3). HR-EIMS m/z : Calcd for C19H26O6, 350.1729. Found, 350.1734 (M+). Anal. Calcd for C19H26O6 : C, 65.13; H, 7.48. Found : C, 64.71; H, 7.67. (5aR*,6R*,9R*,9aS*)-4-Acetyl-6-hydroxy-1-methoxy-9-(1-methylethyl)-3-tosyloxy-6-tosyloxymethyl-5a,6,7,8,9,9a-hexahydrodibenzofuran (19) Yield;84.2 %. Colorless column. mp, 172.9 ~ 174.7C (AcOEt-petroleum ether). 1H-NMR (400 MHz, CDCl3) (: 0.83 (d, 3H, J = 7.0 Hz, (CH3)2CH-), 0.89 (d, 3H, J = 6.8 Hz, (CH3)2CH-), 1.06-1.14 (m , 1H, (CH3)2CHCH-), 1.42-1.50 (m, 3H, -CH2CH2C-OH and 6-OH), 1.73-1.80 (m, 2H, -CH2COH), 1.81 (d7, 1H, J = 2.8, 7.0 Hz, (CH3)2CH-), 2.22 (s, 3H, -COCH3), 2.30 (s, 1H, -OH), 2.47 (s, 6H, Ts-CH32), 3.18 (dd, 1H, J = 5.5, 11.2 Hz, ArCH-), 3.73 (s, 3H, ArOCH3), 4.06, 4.20 (each d, each 1H, J = 9.9 Hz, -CH2OTs), 4.28 (dd, 1H, J = 1.4, 5.3 Hz, ArOCH-), 6.32 (s, 1H, Ar-H), 7.36 (d, 4H, J = 8.1 Hz, Ts-H), 7.78 (d, 2H, J = 8.2 Hz, Ts-H), 7.82 (d, 2H, J = 8.4 Hz, Ts-H). 13C-NMR (100 MHz, CDCl3) ((: 15.3, 16.1, 21.6, 21.67, 21.73, 27.2, 29.7, 31.6, 39.5, 46.3, 55.7, 69.7, 75.0, 87.2, 101.0, 113.2, 120.6, 127.9, 128.7, 129.7, 130.1, 132.2, 132.4, 145.4, 145.5, 146.5, 157.3, 158.8, 195.5. IR (CHCl3) : 3550-3000, 2935, 1724, 1682, 1610, 1361, 1171 cm-1. LR-EIMS : 658 (M+, 9.3), 486 (41.6), 331 (20.2), 207 (55.0), 91 (100.0). HR-EIMS m/z : Calcd for C33H38O10S2, 658.1906. Found, 658.1895 (M+). (5aR*,6R*,9R*,9aS*)-4-Acetyl-6-hydroxy-1-methoxy-6-methyl-9-(1-methylethyl)-3-tosyloxy-5a,6,7,8,9,9a-hexa-hydrodibenzofuran (20) Yield;84.3 %. Colorless oil. 1H-NMR (400 MHz, CDCl3) (: 0.85 (d, 3H, J = 7.0 Hz, (CH3)2CH-), 0.90 (d, 3H, J = 6.8 Hz, (CH3)2CH-), 1.08-1.16 (m, 1H, (CH3)2CHCH-), 1.32-1.48 (m, 2H, -CH2CH2COH), 1.43 (s, 3H, 6-CH3), 1.65 (dt, 1H, J = 4.6, 13.7 Hz, -CH2COH), 1.73-1.79 (m, 1H, -CH2COH), 1.82 (d7, 1H, J = 2.8, 7.0 Hz, (CH3)2CH-), 2.40 (s, 3H, -COCH3), 2.46 (s, 3H, TsCH3), 3.18 (dd, 1H, J = 5.4, 11.2 Hz, ArCH-), 3.75 (s, 3H, ArOCH3), 4.14 (dd, 1H, J = 1.5, 5.3 Hz, ArOCH-), 6.36 (s, 1H, Ar-H), 7.36 (d, 2H, J = 8.6 Hz, Ts-H), 7.84 (d, 2H, J = 8.4 Hz, Ts-H). 13C-NMR (100 MHz, CDCl3) (: 15.4, 17.2, 21.7, 27.2, 28.1, 31.7, 35.0, 39.9, 46.0, 55.7, 69.2, 77.2, 92.0, 100.8, 113.1, 121.1, 128.8, 129.7, 132.5, 145.4, 146.4, 157.5, 159.6, 195.9. IR (CHCl3) : 3500-3000, 3012, 2854, 1723, 1681, 1608, 1371, 1171 cm-1. LR-EIMS : 488 (M+, 31.9), 361 (36.1), 333 (46.0), 319 (41.9), 207 (100.0), 91 (37.9). HR-EIMS m/z : Calcd for C26H32O7S, 488.1868. Found, 488.1874 (M+). ()-Linderol A (1) : [(5aR*,6R*,9R*,9aS*)-4-Cinnamoyl-3,6-dihydroxy-1-methoxy-6-methyl-9-(1-methylethyl)- 5a,6,7,8,9,9a-hexahydrodibenzofuran] Yield: 86.7 %. Yellow powders. mp, 201.2 ~ 202.8C (AcOEt-petroleum ether). 1H-NMR (400 MHz, CDCl3) (:0.85 (d, 3H, J = 7.0 Hz, (CH3)2CH-), 0.91 (d, 3H, J = 6.8 Hz, (CH3)2CH-), 1.14 (tt, 1H, J = 3.5, 11.4 Hz, (CH3)2CHCH-), 1.35-1.49 (m, 2H, -CH2CH2COH), 1.56 (s, 1H, 6-OH), 1.61 (s, 3H, 6-CH3), 1.75 (dt, 1H, J = 4.1, 12.3 Hz, -CH2COH), 1.83 (m, 1H, -CH2COH), 1.86 (d7, 1H, J = 2.9, 7.0 Hz, (CH3)2CH-), 3.14 (dd, 1H, J = 5.5, 11.2 Hz, ArCH-), 3.84 (s, 3H, ArOCH3), 4.24 (dd, 1H, J = 1.5, 5.5 Hz, ArOCH-), 6.09 (s, 1H, Ar-H), 7.38-7.42 (m, 3H, Ph-H), 7.60-7.63 (m, 2H, Ph-H), 7.87, 8.09 (each d, each 1H, J = 15.7 Hz, trans-CH=CH-), 13.97 (s, 1H, ArOH). 13C-NMR (100 MHz, CDCl3) (: 15.4, 17.2, 21.8, 27.2, 28.3, 35.4, 39.5, 46.5, 55.5, 69.4, 92.3, 93.1, 103.3, 113.3, 125.8, 128.4, 128.9, 130.3, 135.4, 143.4, 161.5, 162.2, 166.7, 191.1. IR (CHCl3) : 3395 (3600-3200), 2933, 1630, 1582, 1558, 1494, 1338 cm-1. LR-EIMS : 422 (M+, 48.1), 337 (100.0), 295 (20.7), 249 (11.9), 233 (23.6), 191 (20.0), 131 (21.1). HR-EIMS m/z : Calcd for C26H30O5, 422.2093. Found, 422.2105 (M+). Spectral comparison of the synthetic product [()-1] with the natural product (1)  EMBED ChemDraw.Document.5.0  Table 1. 1H-NMR data PositionNatural product (1) aSynthetic product [()-1]3-OH13.97 (s)13.97 (s)trans-7 and 88.09, 7.86 (d, J=15.6Hz)8.09, 7.87 (d, J=15.6Hz)1-57.61 (m, 2H), 7.39 (m, 3H)7.61 (m, 2H), 7.39 (m, 3H)2-H6.08 (s)6.09 (s)5a-H4.244.24 (dd, J=1.5, 5.5Hz)1-OCH33.84 (s)3.84 (s)9a-H3.143.14 (dd, J=5.5, 11.2Hz)1.75 (m, 1H)1.75 (dt, 1H, J = 4.0, 12.5Hz)6-CH31.61 (s)1.61 (s)6-OH1.58 (br)1.56 (br)1.35 - 1.48 (m, 3H)1.34 - 1.48 (m, 3H)1.14 (m, 1H)1.14 (m, 1H)9-CH(CH3)20.91 (d, J=6.8Hz) 0.85 (d, J=7.0Hz)0.91 (d, J=6.8Hz) 0.85 (d, J=7.0Hz) a) ref.1 Table 2. 13C-NMR data PositionNatural product (1) aSynthetic product [()-1]4-C(=O)-191.1191.13166.7166.71162.2162.24a161.5161.5trans-7 or 8143.4143.41 or 4135.4135.41 or 4130.3130.32, 6128.9128.93, 5128.4128.4trans-7 or 8125.9125.89b113.3113.34103.4103.3293.193.15a92.492.3669.469.455.555.546.546.539.539.5735.435.428.328.327.227.221.821.8817.217.215.415.4 a) ref.1 Table 3. Other Spectral Data IR : n max (cm-1) in KBr tab.UV : max In EtOH (log)EI-MSNatural product (1) a3450, 1635, 1585, 1555, 1495340 nm (4.35)M+: 422.2099 (HR-MS)Synthetic product [()-1]3405, 1630, 1583, 1558, 1495338 nm (4.44)422 (M+, 48.1), 337 (100.0), 295 (20.7), 249 (11.9), 233 (23.6), 217 (9.4), 191 (20.0) 131(21.1), 103 (11.8), 77 (5.5), 58 (12.9) M+: 422.2105 (HR-MS)ref. 1 "<=>@})*89MNPQ`bpqrstľ{{q6OJPJQJ]>*OJPJQJo(6OJPJQJ]o( jdOJPJQJo(H*OJPJQJo(H*OJPJQJo( OJPJQJOJPJQJo( 5OJQJ5OJQJo(56CJ\]o( 5CJ\]5CJ\]o(5B*CJ\o(ph 5CJ\o(o(CJ$o(,; _ ` m>?x$a$(Od](^`O v^v`$a$vXwX)*,-,./123RSW[hjkmno > ? 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