<p> Supporting Information</p><p>Insight into 2α-Chloro-2′(2′,6′)-(Di)Halogenopicropodophyllotoxins</p><p>. Reacting with Carboxylic Acids Mediated by BF3 Et2O</p><p>Lingling Fan1,*, Xiaoyan Zhi1,*, Zhiping Che1 & Hui Xu1,2</p><p>1Research Institute of Pesticidal Design & Synthesis, College of Sciences, Northwest</p><p>A&F University, Yangling 712100, Shaanxi Province, P. R. China.</p><p>2State Key Laboratory of Crop Stress Biology for Arid Areas, Northwest A&F University,</p><p>Yangling 712100, Shaanxi Province, P. R. China.</p><p>Correspondence and requests for materials should be addressed to H.X.</p><p>([email protected]); Telephone: +86(0)29-87091952; Fax: +86(0)29-87091952.</p><p>*These authors contributed equally to this work.</p><p>CONTENTS</p><p>1. Synthesis and characterization ……………………………………………….2-7 2. Comparison of 6e-h and 6e′-h′ about NMR spectra ……..…….………………………..8-11 3. Copies of 1H NMR and 13C NMR spectra ……..…….………………………12-42</p><p>1 1. Synthesis and characterization 1.1. Characterization of 6d-l</p><p> o 20 Data for 6d: Yield: 85%, white solid; m.p. 92-94 C; [α] D = －56 (c 3.2 mg/mL, CHCl3);</p><p>IR cm-1 (KBr): 3047, 2935, 1789, 1736, 1485, 1398, 1110, 1035, 863, 780; 1H NMR (400</p><p>MHz, CDCl3) δ: 7.90-7.93 (m, 2H), 7.84-7.86 (m, 1H), 7.53-7.56 (m, 2H), 7.38-7.47 (m,</p><p>2H), 6.68 (s, 1H, H-5), 6.55 (s, 1H, H-8), 6.43 (s, 1H, H-6′), 5.92 (dd, J = 6.8, 1.2 Hz,</p><p>2H, OCH2O), 5.87 (d, J = 3.2 Hz, 1H, H-4), 5.50 (s, 1H, H-1), 4.73 (d, J = 2.8 Hz, 2H, H-</p><p>11), 4.12 (d, J = 7.2 Hz, 2H, C10H7CH2), 3.94 (s, 3H, 3′-OCH3), 3.89 (s, 3H, 5′-OCH3),</p><p>13 3.72 (s, 3H, 4′-OCH3), 2.99 (dd, J = 6.0, 2.8 Hz, 1H, H-3); C NMR (100 MHz, CDCl3)</p><p>δ: 171.8, 171.7, 152.0, 150.0, 149.2, 148.2, 142.8, 133.9, 132.2, 131.7, 130.6, 129.3,</p><p>129.1, 128.7, 127.9, 126.8, 126.1, 125.5, 123.9, 123.0, 122.1, 108.7, 108.3, 101.7, 75.5,</p><p>72.8, 66.7, 61.14, 61.12, 56.3, 49.2, 44.6, 39.0; HRMS (ESI): Calcd for C34H28O9Cl2Na</p><p>([M+Na]+), 673.1002; found, 673.0973.</p><p> o 20 Data for 6e: Yield: 90%, white solid; m.p. 92-93 C; [α] D = －86 (c 3.3 mg/mL, CHCl3);</p><p>IR cm-1 (KBr): 3076, 2938, 1791, 1742,1486, 1408, 1235, 1021, 873; 1H NMR (400</p><p>MHz, CDCl3) δ: 6.51 (s, 1H, H-5), 6.23 (s, 1H, H-8), 6.07 (s, 1H, H-1), 5.92-5.93 (m, 3H,</p><p>OCH2O, H-4), 4.76-4.78 (m, 1H, H-11), 4.57-4.59 (m, 1H, H-11), 3.98 (s, 3H, 3′-OCH3),</p><p>3.96 (s, 3H, 5′-OCH3), 3.83 (s, 3H, 4′-OCH3), 3.39-3.41 (m, 1H, H-3), 2.24 (s, 3H,</p><p>13 COCH3); C NMR (100 MHz, CDCl3) δ: 172.8, 171.1, 149.3, 148.9, 148.1, 147.6, 147.4,</p><p>133.3, 127.5, 125.9, 125.5, 107.8, 105.7, 101.5, 71.2, 70.9, 64.9, 61.3, 61.28, 61.20, 48.9,</p><p>+ 44.1, 21.1; HRMS (ESI): Calcd for C24H21O9Cl3Na ([M+Na] ), 581.0143; found,</p><p>581.0150.</p><p> o 20 Data for 6f: Yield: 61%, white solid; m.p. 84-86 C; [α] D = － 107 (c 2.8 mg/mL,</p><p>-1 CHCl3); IR cm (KBr): 3076, 2981, 2939, 1790, 1740, 1485, 1408, 1237, 1168, 1031,</p><p>2 1 869; H NMR (400 MHz, CDCl3) δ: 6.49 (s, 1H, H-5), 6.23 (s, 1H, H-8), 6.07 (s, 1H, H-</p><p>1), 5.90-5.93 (m, 3H, OCH2O, H-4), 4.75 (dd, J = 7.2, 3.2 Hz, 1H, H-11), 4.58 (d, J = 7.6</p><p>Hz, 1H, H-11), 3.98 (s, 3H, 3′-OCH3), 3.96 (s, 3H, 5′-OCH3), 3.83 (s, 3H, 4′-OCH3),</p><p>3.382 (dd, J = 5.6, 2.8 Hz, 1H, H-3), 2.49-2.52 (m, 2H, COCH2CH3), 1.23 (t, J = 6.0 Hz,</p><p>13 3H, COCH2CH3); C NMR (100 MHz, CDCl3) δ: 174.4, 172.8, 149.3, 149.0, 148.1,</p><p>147.6, 147.4, 133.3, 127.5, 126.1, 125.5, 107.8, 105.8, 101.4, 71.3, 70.9, 65.0, 61.3, 61.2,</p><p>+ 61.1, 49.1, 44.1, 27.7, 9.1; HRMS (ESI): Calcd for C25H23O9Cl3Na ([M+Na] ), 595.0299; found, 595.0300.</p><p> o 20 Data for 6g: Yield: 71%, white solid; m.p. 78-80 C; [α] D = －95 (c 2.8 mg/mL, CHCl3);</p><p>IR cm-1 (KBr): 3063, 2937, 1790, 1738, 1485, 1408, 1238, 1167, 1024, 699; 1H NMR</p><p>(400 MHz, CDCl3) δ: 7.31-7.378 (m, 5H), 6.34 (s, 1H, H-5), 6.21 (s, 1H, H-8), 6.05 (s,</p><p>1H, H-1), 5.885 (dd, J = 10.0, 1.2 Hz, 2H, OCH2O), 5.86 (d, J = 7.2 Hz, 1H, H-4), 4.65</p><p>(dd, J = 9.2, 4.0 Hz, 1H, H-11), 4.46 (d, J = 9.6 Hz, 1H, H-11), 3.97 (s, 3H, 3′-OCH3),</p><p>3.95 (s, 3H, 5′-OCH3), 3.83 (s, 3H, 4′-OCH3), 3.76 (s, 2H, PhCH2), 3.31 (dd, J = 7.2, 3.6</p><p>13 Hz, 1H, H-3); C NMR (100 MHz, CDCl3) δ: 172.7, 171.6, 149.2, 148.9, 148.1, 147.6,</p><p>147.3, 133.2, 133.1, 129.2, 128.8, 127.6, 127.5, 127.5, 125.8, 125.5, 107.7, 105.8, 101.4,</p><p>71.6, 71.1, 64.9, 61.3, 61.2, 61.1, 49.0, 44.1, 41.5; HRMS (ESI): Calcd for</p><p>+ C30H25O9Cl3Na ([M+Na] ), 657.0456; found, 657.0424.</p><p> o 20 Data for 6h: Yield: 83%, white solid; m.p. 88-90 C; [α] D = －84 (c 3.1 mg/mL, CHCl3);</p><p>IR cm-1 (KBr): 3046, 2935, 1789, 1734, 1484, 1407, 1237, 1167, 1023, 781; 1H NMR</p><p>(400 MHz, CDCl3) δ: 8.02 (d, J = 8.4 Hz, 1H), 7.88-7.90 (m, 1H), 7.82-7.85 (m, 1H),</p><p>7.46-7.59 (m, 4H), 6.32 (s, 1H, H-5), 6.18 (s, 1H, H-8), 6.01 (s, 1H, H-1), 5.87 (dd, J =</p><p>9.2, 1.2 Hz, 2H, OCH2O), 5.84 (d, J = 7.2 Hz, 1H, H-4), 4.53 (dd, J = 9.6, 4.0 Hz, 1H, H-</p><p>3 11), 4.38 (d, J = 9.2 Hz, 1H, H-11), 4.22 (d, J = 0.4 Hz, 2H, C10H7CH2), 3.97 (s, 3H, 3′-</p><p>OCH3), 3.94 (s, 3H, 5′-OCH3), 3.82 (s, 3H, 4′-OCH3), 3.19 (dd, J = 7.2, 4.0 Hz, 1H, H-3);</p><p>13 C NMR (100 MHz, CDCl3) δ: 172.7, 171.7, 149.2, 148.9, 148.1, 147.5, 147.3, 133.9,</p><p>133.1, 131.8, 129.7, 128.9, 128.5, 128.3, 127.5, 127.4, 126.6, 126.0, 125.7, 125.5, 123.4,</p><p>107.7, 106.0, 101.4, 71.9, 71.2, 64.7, 61.3, 61.2, 61.1, 49.0, 44.0, 39.4; HRMS (ESI):</p><p>+ Calcd for C34H27O9Cl3Na ([M+Na] ), 707.0612; found, 707.0640.</p><p> o 20 Data for 6i: Yield: 95%, white solid; m.p. 176-178 C; [α] D = － 94 (c 3.4 mg/mL,</p><p>-1 1 CHCl3); IR cm (KBr): 3051, 2935, 1785, 1735, 1486, 1228, 1107, 1009, 866; H NMR</p><p>(400 MHz, CDCl3) δ: 6.71 (s, 1H, H-5), 6.63 (s, 1H, H-8), 6.60 (s, 1H, H-6′), 5.931-5.95</p><p>(m, 3H, OCH2O, H-4), 5.59 (s, 1H, H-1), 4.80-4.81 (m, 2H, H-11), 3.92 (s, 3H, 3′-OCH3),</p><p>3.88 (s, 3H, 5′-OCH3), 3.76 (s, 3H, 4′-OCH3), 2.97 (dd, J = 5.2, 2.8 Hz, 1H, H-3), 2.15 (s,</p><p>13 3H, COCH3); C NMR (100 MHz, CDCl3) δ: 171.9, 170.6, 152.7, 150.9, 149.2, 148.2,</p><p>142.6, 133.9, 130.9, 123.9, 113.7, 108.76, 108.73, 108.6, 101.7, 75.1, 73.1, 66.8, 61.08,</p><p>+ 61.00, 56.2, 49.4, 47.3, 21.0; HRMS (ESI): Calcd for C24H22O9ClBrNa ([M+Na] ),</p><p>591.0028; found, 591.0028.</p><p> o 20 Data for 6j: Yield: 93%, white solid; m.p. 169-170 C; [α] D = － 83 (c 3.2 mg/mL,</p><p>-1 1 CHCl3); IR cm (KBr): 3074, 2933, 1785, 1733, 1486, 1233, 1171, 1037, 1005, 865; H</p><p>NMR (400 MHz, CDCl3) δ: 6.71 (s, 1H, H-5), 6.62 (s, 1H, H-8), 6.60 (s, 1H, H-6′),</p><p>5.930-5.943 (m, 3H, OCH2O, H-4), 5.59 (s, 1H, H-1), 4.80-4.81 (m, 2H, H-11), 3.92 (s,</p><p>3H, 3′-OCH3), 3.88 (s, 3H, 5′-OCH3), 3.75 (s, 3H, 4′-OCH3), 2.96-2.985 (m, 1H, H-3),</p><p>13 2.35 (q, J = 7.6 Hz, 2H, COCH2CH3), 1.20 (t, J = 7.6 Hz, 3H, COCH2CH3); C NMR</p><p>(100 MHz, CDCl3) δ: 174.2, 171.9, 152.7, 150.9, 149.2, 148.2, 142.7, 134.0, 130.8,</p><p>124.1, 113.7, 108.9, 108.7, 108.5, 101.7, 74.8, 73.1, 66.8, 61.08, 61.00, 56.2, 49.4, 47.2,</p><p>4 + 27.5, 9.0; HRMS (ESI): Calcd for C25H24O9ClBrNa ([M+Na] ), 605.0184; found,</p><p>605.0169.</p><p> o 20 Data for 6k: Yield: 98%, white solid; m.p. 88-90 C; [α] D = －68 (c 3.6 mg/mL, CHCl3);</p><p>IR cm-1 (KBr): 3062, 2935, 1789, 1736, 1484, 1232, 1172, 1006, 864, 696; 1H NMR (400</p><p>MHz, CDCl3) δ: 7.280-7.39 (m, 5H), 6.70 (s, 1H, H-5), 6.59 (s, 1H, H-8), 6.51 (s, 1H, H-</p><p>6′), 5.937 (d, J = 0.8 Hz, 2H, OCH2O), 5.88 (d, J = 3.2 Hz, 1H, H-4), 5.58 (s, 1H, H-1),</p><p>4.78-4.79 (m, 2H, H-11), 3.92 (s, 3H, 3′-OCH3), 3.88 (s, 3H, 5′-OCH3), 3.75 (s, 3H, 4′-</p><p>13 OCH3), 3.67 (d, J = 7.2 Hz, 2H, PhCH2), 2.990 (dd, J = 5.2, 3.2 Hz, 1H, H-3); C NMR</p><p>(100 MHz, CDCl3) δ: 171.8, 171.6, 152.7, 151.0, 149.2, 148.2, 142.7, 133.9, 132.6,</p><p>130.8, 129.0, 128.9, 127.7, 123.8, 113.8, 108.9, 108.6, 108.3, 101.7, 75.4, 72.9, 66.8,</p><p>+ 61.09, 61.01, 56.3, 49.3, 47.2, 41.1; HRMS (ESI): Calcd for C30H26O9ClBrNa ([M+Na] ),</p><p>667.0341; found, 667.0320.</p><p> o 20 Data for 6l: Yield: 92%, white solid; m.p. 90-92 C; [α] D = －67 (c 3.7 mg/mL, CHCl3);</p><p>IR cm-1 (KBr): 3047, 2933, 1788, 1735, 1484, 1231, 1170, 1034, 779; 1H NMR (400</p><p>MHz, CDCl3) δ: 7.90-7.94 (m, 2H), 7.84 (d, J = 7.6 Hz, 1H), 7.540-7.57 (m, 2H), 7.39-</p><p>7.48 (m, 2H), 6.71 (s, 1H, H-5), 6.58 (s, 1H, H-8), 6.43 (s, 1H, H-6′), 5.931 (dd, J = 6.0,</p><p>1.2 Hz, 2H, OCH2O), 5.87 (d, J = 3.2 Hz, 1H, H-4), 5.57 (s, 1H, H-1), 4.741 (d, J = 2.8</p><p>Hz, 2H, H-11), 4.12 (d, J = 7.2 Hz, 2H, C10H7CH2), 3.92 (s, 3H, 3′-OCH3), 3.88 (s, 3H, 5′-</p><p>13 OCH3), 3.72 (s, 3H, 4′-OCH3), 2.99 (dd, J = 6.0, 1.2 Hz, 1H, H-3); C NMR (100 MHz,</p><p>CDCl3) δ: 171.78, 171.75, 152.7, 151.0, 149.2, 148.2, 142.8, 133.98, 133.95, 131.7,</p><p>130.7, 129.3, 129.1, 128.7, 127.9, 126.8, 126.1, 125.5, 123.7, 123.0, 113.8, 109.0, 108.6,</p><p>108.3, 101.7, 75.4, 72.7, 66.7, 61.08, 61.00, 56.3, 49.2, 47.1, 39.0; HRMS (ESI): Calcd</p><p>+ for C34H28O9ClBrNa ([M+Na] ), 717.0497; found, 717.0505.</p><p>5 o 3 o 20 Data for 9: Yield: 52%, white solid, m.p. 264-266 C(lit . m.p. 268-271 C); [α] D = 2 (c</p><p>-1 1 3.0 mg/mL, CHCl3); IR cm (KBr): 3067, 2940, 2910, 1764, 1464,1118, 890; H NMR</p><p>(500 MHz, CDCl3) δ: 7.70 (s, 1H), 7.20 (s, 1H), 7.11 (s, 1H), 6.55 (s, 2H), 6.08 (s, 2H,</p><p>OCH2O), 5.38 (s, 2H), 3.96 (s, 3H, 4′-OCH3), 3.84 (s, 6H, 3′, 5′-OCH3).</p><p>1.2. General procedure for synthesis of 7a-c from 5a-c.</p><p>To solution of 5a-c (0.15 mmol) in dry DCM (5 mL), a solution of BF3·Et2O (0.18 mmol) in dry DCM (5 mL) was added dropwise to keep the temperature below -15 °C.</p><p>After adding, the reaction temperature was raised from -15 °C to r.t., and the reaction process was checked by TLC analysis. When the reaction proceeded for 16-24 h, compounds 5a-c were disappeared. Finally, the mixture was diluted by DCM (30 mL), washed by water (20 mL), HCl (0.1 mol/L, 20 mL), 5% NaHCO3 (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, concentrated in vacuo, and purified by PTLC to give</p><p>7a-c (51-98%) as the white solids.</p><p>1.3. Investigation of 5a not in the presence of BF3·Et2O.</p><p>A solution of 5a (0.031 mmol) in dry DCM (5 mL) was stirred at r.t. for 2 weeks, and no new product was checked by TLC. </p><p>1.4. Investigation of 5c in the presence of BF3·Et2O at the different temperatures.</p><p>To a solution of 5c (0.057 mmol) in dry DCM (5 mL) at -78 °C, a solution of BF3·Et2O</p><p>(0.068 mmol) in dry DCM (2 mL) was added dropwise to keep the temperature below -78</p><p>°C. After adding, the reaction was maintained at this temperature for 5.5 h, there was no new product checked by TLC. Similarly, at -40 °C for 20 h, or -15 °C for 24 h, no new product was detected.</p><p>1.5. Investigation of 5c in the presence of BF3·Et2O at the different temperatures.</p><p>6 A solution of 5c (0.057 mmol) and AlCl3 (0.068 mmol) in dry DCM (5 mL) was cooled at -15 °C for 20 min, then the reaction temperature was raised from -15 °C to r.t. for 24 h.</p><p>Finally, the mixture was concentrated in vacuo, and purified by PTLC to give 7c in 77% yield as a white solid.</p><p>1.6. Investigation of 8a in the presence of BF3·Et2O.</p><p>To a solution of 8a (0.145 mmol) in dry DCM (5 mL) at -15 °C, a solution of BF3·Et2O</p><p>(0.174 mmol) in dry DCM (5 mL) was added dropwise to keep the temperature below -15</p><p>°C. After adding, the reaction temperature was raised from -15 °C to r.t. When the reaction proceeded for 48 h, the mixture was diluted by DCM (30 mL), washed by water</p><p>(20 mL), HCl (0.1 mol/L, 20 mL), 5% NaHCO3 (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, concentrated in vacuo, and purified by PTLC to give 9 in 52% yield as a white solid.</p><p>1.7. Investigation of 8b in the presence of BF3·Et2O.</p><p>To a solution of 8b (0.15 mmol) in dry DCM (5 mL) -15 °C, a solution of BF3·Et2O</p><p>(0.18 mmol) in dry DCM (5 mL) was added dropwise to keep the temperature below -15</p><p>°C. After adding, the reaction temperature was raised from -15 °C to 9 °C. If the reaction proceeded for 24 h, there was no new product checked by TLC. Then the mixture was reacted at 40°C for 48 h, no new product was detected.</p><p>References:</p><p>(1) Petcher, T. J.; Weber, H. P.; Kuhn, M.; von Wartburg. A. J. Chem. Soc. 1973, 3, 288－ 292. (2) Xu, H.; Xiao, X.; Wang, Q. T. Bioorg. Med. Chem. Lett. 2010, 20, 5009−5012.</p><p>(3) Nishii, Y.; Yoshida, T.; Asano, H.; Wakasugi, K. et al. J. Org. Chem. 2005, 70, 2667- 2678.</p><p>7 2. Comparison of 6e-h and 6e′-h′ about NMR spectra 6e (1H NMR) 0 9 2 9 5 2 6 7 9 6 0 2 0 6 3 2 8 9 0 3 3 2 8 9 7 8 1 9 6 1 7 3 6 6 3 0 4 0 2 9 9 7 5 5 9 4 3 2 5 0 9 7 9 8 4 2 0 ...... 7 6 6 6 5 5 5 4 4 4 4 3 3 3 3 3 3 2 0</p><p>. BF3 Et2O 5b Acetic acid 6e</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 1 5 0 1 8 9 9 5 9 9 0 0 0 0 1 0 1 0 9 9 ...... 1 1 1 3 1 1 6 3 0 2 6e′ (1H NMR) 9 8 5 3 3 6 2 6 0 2 0 7 3 1 5 3 7 8 8 0 2 3 6 1 3 1 8 6 1 7 2 8 9 7 8 6 0 9 4 0 2 9 7 0 8 4 5 2 5 0 9 7 5 5 9 9 4 3 2 0 ...... 7 6 6 6 5 5 4 4 4 4 4 3 3 3 3 3 3 2 1 0</p><p>DCC/DMAP 5b Acetic acid 6e'</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 4 5 5 8 3 6 0 4 4 3 5 0 1 0 0 0 0 0 0 0 2 0 ...... 1 1 1 3 1 1 3 3 3 1 3 6e (13C NMR) 9 1 3 7 1 4 0 4 1 7 2 2 1 8 1 1 9 2 3 7 5 2 5 7 1 9 6 0 6 3 0 5 8 8 1 3 8 9 4 5 1 3 9 6 9 8 7 5 0 9 9 8 0 1 8 1 4 3 5 5 5 6 6 8 8 5 ...... 3 7 9 3 2 1 ...... 0 2 9 2 9 1 1 9 8 7 5 7 5 1 ...... 2 8 7 3 7 5 ...... 7 7 4 4 4 4 4 3 2 2 2 0 0 0 7 7 6 1 0 4 1 1 1 8 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 6 4 4 2</p><p>. BF3 Et2O 5b Acetic acid 6e</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 6e′ (13C NMR) 1 1 7 2 0 7 9 8 1 4 0 3 8 3 5 9 8 2 7 2 6 5 4 1 8 1 9 1 4 1 7 0 1 8 4 6 2 5 4 8 8 0 9 1 5 9 5 8 7 5 3 2 4 8 7 9 7 3 6 3 3 5 6 7 0 3 ...... 3 0 7 2 9 9 3 2 1 9 1 1 2 1 9 8 8 7 7 3 7 5 5 7 5 1 ...... 7 7 4 4 4 4 4 3 2 2 2 0 0 0 7 7 6 1 0 4 1 1 1 8 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 6 4 4 2</p><p>DCC/DMAP 5b Acetic acid 6e'</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>8 6f (1H NMR) 1 4 4 9 6 9 2 6 9 8 0 7 9 2 1 0 4 7 0 3 8 3 3 8 8 3 6 5 0 5 0 6 9 7 1 7 6 0 8 3 0 9 8 2 1 8 6 3 3 3 1 8 6 8 6 9 3 0 9 4 5 0 2 4 0 9 7 7 6 9 8 4 3 3 5 5 4 2 2 2 9 9 7 7 5 9 3 5 5 4 5 2 0 ...... 7 6 6 6 5 5 5 4 4 4 4 4 4 3 3 3 3 3 3 3 2 2 2 2 2 2 1 1 1 1 0</p><p>BF .Et O 5b Propionic acid 3 2 6f</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 0 9 7 7 0 6 5 8 9 3 0 2 5 9 4 0 0 9 0 0 1 ...... 1 1 1 2 1 1 5 2 1 2 3 6f′ (1H NMR) 6 5 8 8 4 1 4 3 3 4 6 0 5 4 0 6 2 5 7 8 5 7 9 2 0 6 7 3 8 1 9 8 6 4 2 8 5 9 3 2 6 3 0 9 8 0 8 6 3 0 2 4 2 0 9 9 7 7 6 5 9 9 8 4 3 3 5 5 5 4 5 2 2 2 0 ...... 7 6 6 6 5 5 4 4 4 4 3 3 3 3 3 3 2 2 2 2 1 1 1 1 0</p><p>DCC/DMAP 5b Propionic acid 6f'</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 8 9 9 1 0 9 3 6 5 8 1 0 9 9 0 0 0 0 0 0 0 2 ...... 1 0 0 3 1 1 6 3 1 2 3 6f (13C NMR) 2 2 2 8 3 7 7 9 1 7 1 8 0 2 8 3 2 2 3 1 0 3 9 1 6 4 2 7 5 0 7 7 3 4 4 8 3 6 5 2 4 8 3 0 1 3 6 1 5 1 3 7 6 4 5 1 5 8 8 4 0 5 4 3 5 6 0 ...... 2 0 7 3 9 0 3 2 1 1 1 7 9 4 2 9 9 8 7 7 3 7 6 5 7 5 1 ...... 1 7 7 4 4 4 3 7 7 6 5 9 7 4 4 2 2 2 0 0 0 1 0 1 1 1 4 . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 6 4 4 2 9</p><p>BF .Et O 5b Propionic acid 3 2 6f</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 6f′ (13C NMR) 4 3 1 8 2 5 7 0 8 8 1 5 1 6 7 2 8 9 8 0 0 8 1 8 3 8 5 5 0 9 8 0 3 7 9 9 0 4 2 3 5 5 8 2 9 5 5 0 5 5 0 7 7 7 8 6 7 5 1 6 3 3 8 8 4 4 2 4 9 2 ...... 3 0 7 3 9 9 3 2 1 0 1 7 0 2 9 8 7 7 6 5 ...... 2 4 8 7 7 3 7 5 1 . . . . . 7 4 4 2 2 2 2 7 0 4 1 1 9 7 . 7 4 4 4 3 0 0 0 7 6 1 1 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 6 4 4 2 9</p><p>DCC/DMAP 5b Propionic acid 6f'</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>9 6g (1H NMR) 8 3 0 6 9 2 1 0 9 9 7 3 9 5 8 5 6 4 0 0 8 3 8 5 1 2 2 9 4 3 4 6 0 7 4 3 2 1 1 5 1 7 6 8 6 7 3 6 2 6 7 6 6 4 1 8 8 6 9 8 5 5 4 3 1 0 3 3 3 3 3 3 3 2 3 2 0 9 9 8 8 8 8 6 6 6 6 4 4 9 9 8 7 3 3 3 3 5 0 ...... 7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 5 5 4 4 4 4 4 4 3 3 3 3 3 3 3 3 1 0</p><p>BF .Et O 5b phenylacetic acid 3 2 6g</p><p>8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 1 7 1 4 0 2 2 0 0 2 2 2 8 0 0 0 0 0 1 0 0 0 0 0 0 0 ...... 5 1 1 1 2 1 1 1 3 3 3 2 1 6g′ (1H NMR) 0 8 0 3 5 8 3 8 3 8 5 1 1 1 8 0 7 1 6 6 1 1 2 4 9 0 9 8 6 4 2 6 4 1 4 1 9 6 9 6 9 6 8 5 3 7 4 3 2 8 0 . 3 3 3 3 3 2 3 2 0 9 8 8 6 6 4 4 9 9 8 7 3 3 3 5 ...... 0 7 7 7 7 7 7 6 6 6 5 5 5 4 4 4 4 3 3 3 3 3 3 3 1 -</p><p>DCC/DMAP 5b phenylacetic acid 6g'</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 8 0 9 6 5 5 1 6 1 7 2 1 0 9 0 1 0 0 2 1 9 0 ...... 5 1 0 1 3 1 1 6 3 1 1 6g (13C NMR) 6 2 7 4 0 1 9 7 7 3 8 2 6 4 7 6 8 9 9 6 9 9 9 6 1 7 4 8 7 7 1 7 3 0 6 7 4 6 2 4 5 7 5 1 2 3 6 4 8 8 7 6 2 3 2 1 2 6 5 5 5 7 8 4 4 1 9 1 5 4 5 0 8 9 1 6 8 8 2 0 4 ...... 3 0 7 6 1 9 3 2 1 0 1 5 2 1 9 7 3 3 9 7 7 7 5 7 5 1 ...... 8 8 7 8 5 . . . 7 7 4 4 3 3 2 2 2 2 2 0 0 0 7 1 1 4 1 1 1 4 1 4 4 4 2 2 7 6 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 6 4 4 4</p><p>BF .Et O 5b phenylacetic acid 3 2 6g</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 6g′ (13C NMR) 3 5 0 2 2 6 8 0 0 5 9 7 3 8 6 7 0 9 1 0 2 8 8 5 1 7 3 8 9 9 2 7 1 9 6 9 4 9 4 6 9 8 5 0 6 2 6 6 5 5 8 7 9 1 6 3 2 1 2 7 5 2 0 2 0 2 2 8 6 5 5 7 8 4 6 4 7 7 8 9 8 ...... 3 0 7 6 2 9 3 2 1 0 0 5 2 1 9 8 8 7 7 3 3 9 8 7 7 7 5 5 7 5 1 ...... 7 7 4 4 4 4 3 3 2 2 2 6 1 1 4 9 4 2 2 2 2 0 0 0 7 7 1 1 1 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 6 4 4 4</p><p>DCC/DMAP 5b phenylacetic acid 6g'</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>10 6h (1H NMR) 0 8 7 5 6 3 0 7 6 5 2 8 4 1 7 3 9 6 7 7 2 8 7 6 1 9 6 7 3 5 7 3 3 9 9 0 7 1 0 1 0 5 0 1 3 3 8 0 5 2 9 9 7 7 7 6 5 2 8 1 7 6 4 3 8 2 1 0 9 6 4 2 0 8 8 3 7 5 5 3 3 6 9 9 7 7 6 4 1 2 7 4 2 2 0 . 0 0 9 8 8 8 8 8 5 5 5 5 5 5 5 5 5 4 4 4 2 3 1 0 8 8 8 8 8 8 5 5 5 5 4 3 2 2 9 9 8 2 2 2 1 5 ...... 0 8 8 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 5 5 4 4 4 4 4 4 4 4 3 3 3 3 3 3 3 1 -</p><p>BF .Et O 5b Naphthaleneacetic Acid 3 2 6h</p><p>9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 4 8 0 6 1 3 5 0 0 3 4 0 2 2 9 0 0 0 1 0 0 0 0 0 0 0 0 9 1 1 0 0 ...... 1 1 1 4 1 1 1 2 1 1 1 1 3 3 3 1 6h′ (1H NMR) 0 7 8 3 9 3 7 1 0 9 1 8 2 6 2 7 1 6 8 7 9 2 3 9 8 3 6 9 3 3 4 9 3 2 0 4 0 4 5 2 7 6 3 0 8 4 7 1 4 2 1 2 8 9 7 4 0 6 8 0 6 4 9 2 7 1 0 8 0 . 0 9 8 5 5 4 2 3 0 8 8 5 4 9 8 2 0 8 5 5 5 5 4 1 9 8 5 3 2 9 2 2 5 ...... 0 8 8 7 7 7 7 7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 4 4 4 4 4 3 3 3 3 3 3 1 -</p><p>DCC/DMAP 5b Naphthaleneacetic Acid 6h'</p><p>8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 7 5 0 9 8 3 0 2 0 1 5 1 6 3 2 2 0 0 0 0 0 0 1 2 0 0 0 0 ...... 1 2 4 1 1 1 3 1 1 2 3 3 3 1 6h (13C NMR) 9 6 1 7 5 5 5 3 9 8 2 0 6 8 7 7 0 0 6 5 9 3 3 9 1 4 6 4 5 9 4 3 0 4 7 8 1 1 5 6 5 1 1 7 7 2 1 4 1 2 4 8 4 2 2 4 7 0 3 9 7 7 2 8 7 9 3 5 4 7 0 4 4 9 4 6 0 9 1 5 3 9 1 5 6 0 5 4 7 2 0 4 4 2 3 6 ...... 3 0 7 9 2 7 3 2 1 0 0 4 2 1 9 1 9 8 8 7 7 5 6 1 . . . . . 8 8 7 7 3 3 8 6 6 5 3 7 ...... 7 7 4 3 2 2 2 2 2 2 0 0 7 4 1 4 9 4 4 4 4 3 3 2 2 2 2 2 0 7 6 1 1 1 1 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 6 4 4 3</p><p>BF .Et O 5b Naphthaleneacetic Acid 3 2 6h</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 6h′ (13C NMR) 8 1 4 7 1 1 5 6 4 8 9 7 5 2 5 4 1 1 4 7 3 5 8 5 3 5 0 2 0 3 3 7 3 9 8 5 7 2 0 6 8 3 4 6 9 4 6 5 0 3 8 6 1 4 7 7 2 9 1 6 9 1 8 5 6 0 5 4 4 2 8 7 5 4 2 3 7 9 3 5 4 7 6 4 7 7 5 ...... 3 0 7 9 2 7 3 2 1 0 0 4 2 1 9 8 8 7 3 3 1 8 6 6 5 3 ...... 7 9 8 8 7 7 5 . . . . . 7 7 4 4 4 4 3 3 3 2 2 2 2 2 7 6 4 1 1 9 9 4 2 2 2 2 2 2 7 1 1 1 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 6 4 4 3</p><p>DCC/DMAP 5b Naphthaleneacetic Acid 6h'</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>11 3. Copies of 1H NMR and 13C NMR spectra</p><p>O 6 0 1 7 4 6 8 0 4 0 0 3 0 9 3 9 0 8 9 6 8 4 8 5 3 0 4 7 6 0 4 2 1 1 8 6 8 7</p><p>2 6 6 5 9 9 9 5 8 8 8 9 8 7 O 9 9 9 1 0 ...... 7 6 6 6 5 5 5 5 4 4 4 3 3 3 2 2 2 2 0 O O O Cl O Cl</p><p>MeO OMe OMe 6a</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 7 0 1 8 4 1 8 8 1 7 1 0 0 0 1 0 0 1 0 1 0 0</p><p>...... 12 . . 1 1 1 3 1 2 3 3 3 1 3 O</p><p>O 7 6 7 1 6 8 8 1 3 0 8 3 3 9 9 9 6 7 8 5 2 9 3 2 4 2 3 6 1 4 7 3 8 3 4 4 8 0 5 3 4 3 9 6 0 9 2 2 6 1 8 9 0 8 6 3 7 8 2 7 9 0 3 4 2 6 4 0 0</p><p>...... O. . 2 0 7 1 2 8 1 1 1 3 7 1 1 2 9 2 2 0 3 2 8 1 ...... 0 9 8 8 8 ...... 7 5 4 4 3 3 2 2 0 0 7 6 6 1 9 1 7 4 4 0 0 7 5 3 O 1 6 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 5 4 4 2 O Cl O Cl</p><p>MeO OMe OMe 6a</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 13 O 0</p><p>4 8 6 9 4 1 5 2 6 6 6 7 7 0 O 5 9 1 4 5 8 9 7 4 5 6 0 6 7 2 7 4 4 3 3 1 1 0 3 8 5 7 6 6 2 0 7 5 8 4 2 0 0 6 5 8 8 9 8 7 3 3 5 2 2 . 2 6 9 9 9 9 5 9 9 9 4 4 2 ...... 0 ...... </p><p>7 6 6 6 5 5 5 5 5 4 4 O 3 3 3 2 2 2 2 2 2 2 1 1 1 1 - O O Cl O Cl</p><p>MeO OMe OMe 6b</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 9 2 1 0 7 2 5 8 9 0 0 9 0 0 0 0 0 2 0 0 0 9 0 ...... 1 0 1 3 1 2 3 3 3 0 2 3</p><p>14 O</p><p>1 4 1 0 6 9 7 0 6 6 5 4 4 6 9 O 8 9 9 2 3 3 0 3 6 1 1 2 7 4 1 6 1 9 2 4 4 9 6 9 0 2 2 2 9 0 0 2 2 8 2 7 2 1 8 6 5 7 4 3 0 2 6 8 2 1 8 0 1 9 5 ...... 3 2 7 9 1 8 1 1 2 4 7 5 2</p><p>4 1 2 0 9 8 2 2 0 4 2 8 8 8 1 O ...... 0 7 7 5 5 4 4 4 3 3 2 2 0 0 0 0 7 7 6 4 3 6 1 1 6 9 4 7 . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 O6 6 5 4 4 2 9 O Cl O Cl</p><p>MeO OMe OMe 6b</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>15 0 5 8 4 9 5 2 5 8 0 0 2 9 0 2 1 8 9 6 8 0 8 8 9 8 2 2 4 7 8 4 0 0 9 7 7 5 4 4 3 2 1 9 8 7 6 7 7 1 3 3 9 9 0 8 7 3 9 5 9 7 9 9 8 0 3 3 3 3 2 2 2 5 5 9 8 5 7 7 9 . 3 3 3 3 3 2 6 9 8 7 9 8 6 6 9 5 ...... 0 ...... O...... 7 7 7 7 7 7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 5 4 4 3 3 3 3 3 2 2 1 -</p><p>O O O O Cl O Cl</p><p>MeO OMe OMe 6c</p><p>8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 7 0 0 7 1 9 8 2 8 8 2 9 9 9 9 0 0 1 9 9 1 9 0 0 0 9 ...... 5 0 0 0 2 0 0 2 3 3 3 2 0</p><p>16 O 5 7 1 9 0 7 1 1 9 3 1 5 7 7 3 8 2 5 9 9 6 4 6 8 8 8 6 6 5 3 9 1 2 5 6 3 3 7 5 2 4 4 9 O8 4 9 1 1 8 4 8 6 0 0 2 2 8 6 1 6 0 9 7 9 1 7 6 4 7 4 2 0 0 6 9 3 2 4 8 2 3 ...... 3 0 7 5 9 7 1 1 3 2 6 1 1 2 0 9 2 2 0 9 7 3 2 8 8 1 . . . . . 1 8 2 8 8 ...... 7 5 5 4 3 3 3 2 2 2 2 0 0 0 7 7 1 9 4 7 4 4 2 0 O 6 5 2 6 1 6 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 O6 6 5 4 4 4 O Cl O Cl</p><p>MeO OMe OMe 6c</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 17 6 0 8 2 0 3 1 1 7 9 9 9 7 7 0 6 2 6 7 2 2 7 6 9 1 8 0 3 6 0 4 8 7 4 7 8 3 5 1 5 5 0 7 0 3 3 2 1 0 0 6 4 6 6 6 5 4 4 3 7 6 3 0 8 5 8 5 3 4 4 3 2 8 7 0 4 3 4 2 4 9 2 1 0 9 9 6 0 9 9 9 9 8 5 5 5 4 4 3 5 4 9 9 8 5 7 1 8 0 9 9 9 8 5 5 5 5 4 4 2 6 9 9 8 7 1 9 7 0 9 5 0 ...... O ...... 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 5 5 5 4 4 4 4 3 3 3 3 3 2 2 1 0 O O O O Cl O Cl</p><p>MeO OMe OMe 6d</p><p>10 9 8 7 6 5 4 3 2 1 0 ppm 3 3 2 1 0 9 6 6 0 0 0 4 1 3 1 3 1 0 0 0 0 0 0 0 0 0 0 9 0 8 0 0 ...... 2 1 2 2 1 1 0 2 1 1 2 1 3 3 3 1 18 4 6 7 0 8 7 7 8 8 2 8 3 8 2 4 5 4 2 8 5 7 3 8 3 6 5 5 8 6 0 4 3 0 6 1 9 6 4 6 5 8 3 0 5 7 1 5 1 4 5 0 9 5 2 7 0 4 4 2 4 8 0 2 8 7 6 1 7 8 1 9 7 3 4 2 4 3 4 8 7 0 2 9 2 3 9 5 0 1 7 0 7 2 5 0 6 ...... 3 0 5 8 1 3 ...... O7 7 1 2 6 0 1 1 2 0 9 8 2 3 2 1 0 9 9 8 7 6 6 5 3 3 2 8 8 1 ...... 7 7 5 5 4 4 4 3 3 3 3 2 2 2 2 2 2 2 2 2 2 0 0 0 7 7 6 5 2 6 1 1 6 9 4 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 O7 7 6 6 6 5 4 4 3 O O O Cl O Cl</p><p>MeO OMe OMe 6d</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>19 O 6 0 0 2 9 0 2 9 6 5 2 6 3 2 7 8 9 9 0 6 1 3 7 3 3 2 8 6 9 7 8 6 3 1 0 9 4 0 0 9 7 7 5 9 9 4 0 2 5 2 9 9 5 8 4 3 2 ...... </p><p>7 6 6 6 5 5 5 4 4 4 4 3 3 3 O3 3 3 2 0 O O O Cl O Cl Cl</p><p>MeO OMe OMe 6e</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 1 1 8 9 5 9 5 9 9 0 1 0 0 9 0 0 1 0 9 ...... 1 1 1 3 1 1 6 3 0 2 20 O</p><p>9 1 3 7 1 4 0 4 1 7 2 2 1 8 O 6 1 1 9 3 2 0 5 8 3 8 7 5 2 5 1 7 3 1 8 9 9 6 4 0 5 8 1 3 9 1 6 4 3 5 9 5 8 7 5 0 5 9 6 9 6 8 8 0 8 1 5 ...... 3 0 7 2 9 9 3 2 2 9 1 1 2 1 9 8 8 7 7 3 7 5 5 7 5 1 ...... </p><p>7 7 4 4 4 4 4 3 2 2 2 0 0 O0 7 7 6 1 0 4 1 1 1 8 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 O6 6 6 4 4 2 O Cl O Cl Cl</p><p>MeO OMe OMe 6e</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>21 1 4 4 9 5 0 8 0 8 5 7 7 9 6 7 1 1 0 4 6 9 2 2 3 7 8 1 5 0 5 0 6 9 3 7 3 2 1 1 0 8 7 6 5 0 8 8 6 3 0 9 8 8 2 1 0 9 5 6 5 3 0</p><p>2 4 2 0 9 9 9 9 9 7 7 7 7 6 5 9 9 O8 4 3 3 3 5 5 5 4 5 2 2 2 0 ...... 7 6 6 6 5 5 5 5 5 4 4 4 4 4 4 3 3 3 3 3 3 3 2 2 2 2 1 1 1 1 0 O O O O Cl O Cl Cl</p><p>MeO OMe OMe 6f</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 4 4 6 7 9 4 5 9 4 1 0 0 0 0 0 0 0 0 0 1 3 ...... 1 1 1 3 1 1 6 3 1 2 3</p><p>22 O</p><p>2 2 2 8 3 7 9 7 1 7 1 8 0 2 O 8 3 3 9 4 2 8 2 2 3 1 0 1 6 7 5 0 7 7 3 4 4 3 6 5 2 4 8 3 0 1 6 4 3 5 1 5 8 8 4 6 1 5 0 5 1 4 3 5 3 6 7 0 ...... 2 ...... 2 0 7 3 9 0 3 1 1 1 7 9</p><p>4 2 9 9 8 7 7 3 7 6 5 7 O5 1 ...... 1 7 7 3 2 0 0 1 4 4 4 4 4 2 2 0 7 7 6 1 0 5 1 1 9 4 7 . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 O6 6 6 6 4 4 2 9 O Cl O Cl Cl</p><p>MeO OMe OMe 6f</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>23 O 8 4 0 9 1 2 2 9 9 7 3 9 4 5 8 3 4 5 6 6 0 3 0 6 9 0 8 2 1 3 0 8 5 7 7 6 4 3 2 1 6 4 1 5 1 1 8 8 7 6 9 8 6 5 8 6 7 5 3 6 4 3 2 1 6 0 3 3 3 3 3 3 3 2 3 2 0 9 9 8 8 8 8 6 6 6 6 4 4 9 9 8 7 3 3 3 3 5 0 ...... </p><p>7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 5 5 4 4 4 4 4 4 3 3 3 3 3 O3 3 3 1 0 O O O Cl O Cl Cl</p><p>MeO OMe OMe 6g</p><p>8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 0 1 2 7 1 4 2 2 8 0 2 2 0 0 0 0 0 1 0 0 0 0 0 0 0 ...... 5 1 1 1 2 1 1 1 3 3 3 2 1 24 O</p><p>6 2 7 4 0 1 9 7 7 3 8 2 6 4 7 6 8 9 9 O 6 9 9 9 6 1 7 4 8 7 7 1 7 3 0 6 7 4 6 2 4 5 7 5 1 2 3 6 4 8 8 6 9 1 2 8 6 8 8 2 9 1 4 8 7 2 6 3 1 2 5 5 5 7 4 4 0 1 5 5 4 0 ...... 3 0 7 6 1 9 3 2 1 0 1 5 1 8 8 3 8 7 5 5 . . . . . 2 9 7 7 3 9 7 7 5 7 1 ...... 7 4 4 3 2 2 2 0 7 1 4 1 1 7 4 4 4 3 2 2 2 2 0 0 O 7 6 1 1 1 9 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 O6 6 4 4 4 O Cl O Cl Cl</p><p>MeO OMe OMe 6g</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>25 O 0 8 7 5 6 3 0 7 6 5 2 8 4 1 7 3 9 6 7 7 2 8 7 6 1 9 6 7 3 5 7 3 3 9 9 0 7 1 0 1 0 5 0 1 3 3 8 0 2 0 8 3 2 7 7 3 7 6 2 8 7 7 6 4 8 2 2 2 2 1 6 4 8 5 9 9 7 5 5 3 6 5 1 9 9 6 4 7 3 1 7 4 0 9 0 0 9 8 8 8 5 5 5 4 4 3 1 8 8 5 5 3 2 2 8 2 2 5 0 8 8 5 5 5 5 5 5 4 2 0 8 8 8 8 5 5 4 9 9 2 1 ...... 0</p><p>8 8 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 5 5 O4 4 4 4 4 4 4 4 3 3 3 3 3 3 3 1 - O O O Cl O Cl Cl</p><p>MeO OMe OMe 6h</p><p>10 9 8 7 6 5 4 3 2 1 0 ppm 4 6 0 1 0 0 0 4 8 0 3 5 2 2 9 3 0 0 0 0 0 1 1 0 0 1 0 0 0 0 9 0 ...... 1 1 1 4 1 1 1 2 1 1 1 1 3 3 3 1 26 9 6 7 5 5 5 9 8 0 8 7 0 6 5 3 1 3 2 6 7 0 9 3 9</p><p>1 4 6 4 5 9 4 3 0 4 7 8 1 1 5 6 5 1 1 7 7 2 1 4 O1 2 4 8 4 2 2 4 7 0 3 9 7 7 9 1 5 3 1 8 9 3 5 6 7 5 7 4 2 4 9 4 3 0 2 9 7 5 4 0 4 0 4 0 4 2 6 6 ...... 3 0 9 7 3 1 4 ...... 7 2 2 0 0 2 1 9 8 8 7 7 3 3 1 9 8 8 8 7 7 6 6 5 5 3 7 6 1 ...... 7 7 4 4 4 4 3 3 2 2 2 2 2 2 0 7 7 1 4 1 1 9 4 3 2 2 2 2 2 0 0 6 1 1 9 4</p><p>1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 O7 7 7 6 6 6 6 4 4 3 O O O Cl O Cl Cl</p><p>MeO OMe OMe 6h</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>27 O 0 4 7 8 9 0 7 8 4 7 0 9 5 8 9 0 5 1 5 3 4 7 9 0</p><p>6 1 3 0 5 4 3 3 3 9 1 1 0 2 8 6 O 9 9 8 7 5 9 0 7 9 9 5 8 8 9 8 9 9 1 2 6 6 9 9 9 8 7 9 9 5 ...... 0 7 6 6 6 5 5 5 5 5 5 4 4 4 O 3 3 3 2 2 2 2 2 1 - O O Cl O Br</p><p>MeO OMe OMe 6i</p><p>7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 1 0 3 8 3 1 1 1 0 0 0 0 0 0 0 0 0 9 0 0 2 ...... 1 1 1 3 0 2 3 3 3 1 3</p><p>28 O</p><p>O</p><p>4 4 4 1 4 3 7 5 8 5 7 1 O1 7 8 1 9 9 8 2 6 3 0 3 9 1 0 1 6 3 3 2 8 6 6 8 5 7 3 5 9 4 9 6 7 9 2 2 6 9 9 9 7 7 7 6 7 4 2 1 4 6 6 8 0 1 3 2 9 ...... 0 7 1 8 0 3 0 ...... 3 O1 0 2 4 1 0 2 0 9 8 2 3 0 3 3 8 8 8 1 ...... 7 5 4 3 2 0 0 0 0 7 6 3 6 1 7 1 7 5 4 4 3 1 O 7 5 1 6 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 6 6 5 4 4 2 Cl O Br</p><p>MeO OMe OMe 6i</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 29 O 0 4 0 3 0 3 0 5 5 3 4 5 5 6 7 6 3 2 7 7 2 6 8 4 7 8 0 6 1 4 4 3 3 9 2 8 5 8 0 7 5 4 2 0 1 0 O 8 7 6 2 2 0 0 2 7 6 6 9 9 9 9 5 8 8 9 8 7 9 9 9 9 4 4 3 3 2 2 2 ...... 0 7 6 6 6 5 5 5 5 5 4 4 O 3 3 3 2 2 2 2 2 2 2 2 1 1 1 - O O Cl O Br</p><p>MeO OMe OMe 6j</p><p>7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 9 6 4 5 8 0 0 2 4 9 1 0 0 0 1 9 0 0 0 0 9 1 0 ...... 1 1 1 3 0 2 3 3 3 0 2 3</p><p>30 O</p><p>8 5 8 9 3 1 1 4 7 0 0 9 2 0 0 O 8 3 7 7 0 5 4 3 7 0 8 5 0 1 2 7 8 0 9 8 6 5 1 2 2 4 4 2 9 7 9 2 2 7 0 5 3 2 5 4 9 8 0 9 7 8 1 7 9 7 5 7 3 9 9 ...... 3 0 7 8 1 8 0 0 2 3 ...... 4 2 5 4 1 2 0 9 8 2 4 ...... 0 0 4 3 8 8 8 O1 . . . 7 7 5 5 4 4 4 3 3 2 1 0 0 0 0 7 7 6 4 3 6 1 1 6 9 7 7 . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 O6 6 6 5 4 4 2 9 O Cl O Br</p><p>MeO OMe OMe 6j</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>31 O 0 7 0 6 2 2 8 4 0 4 0 1 2 3 3 9 7 7 9 6 2 3 7 8 3 4 6 2 3 8 0 8 0</p><p>9 8 7 6 5 4 4 3 8 8 6 0 9 1 3 3 9 8 8 9 8 2 8 5 O9 7 1 0 9 9 5 0 3 3 3 3 3 3 3 3 2 2 2 7 5 5 9 9 8 8 5 7 7 9 8 7 6 6 0 0 9 9 5 ...... 0 7 7 7 7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 5 4 O4 3 3 3 3 3 3 3 2 2 1 - O O Cl O Br</p><p>MeO OMe OMe 6k</p><p>8 7 6 5 4 3 2 1 0 ppm 0 0 2 8 9 9 9 6 0 7 4 9 9 0 0 0 9 0 9 9 0 1 0 0 0 9 ...... 5 1 1 0 2 0 0 2 3 3 3 2 0</p><p>32 O 3 5 6 5 5 5 5 6 0 4 1 8 3 6 1 3 7 9 9 5 1 8 9 2 1 8 8 5 3 9 4 1 3 3 6 4 4 8 8 9 0 7 6 9 4 1 8 9 7 2 O 8 6 7 0 2 2 7 9 6 8 0 9 7 8 8 9 6 3 7 4 2 1 5 4 0 9 1 4 3 1 5 . . 3 0 7 4 9 8 0 0 3 3 2 1 ...... 1 1 2 1 9 8 2 3 2 0 9 8 7 3 3 8 8 8 1 ...... 5 5 7 7 6 5 2 6 1 1 6 9 7 1 7 7 4 4 4 3 3 3 2 2 2 2 1 0 0 0 O0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 7 7 7 6 O6 6 5 4 4 4 O Cl O Br</p><p>MeO OMe OMe 6k</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>33 0 4 9 2 6 1 6 4 3 4 9 4 7 9 4 0 0 2 2 6 0 0 4 0 1 9 6 4 1 6 8 7 8 1 6 8 9 8 4 6 9 1 4 6 0 4 3 2 2 1 1 0 6 4 7 6 6 5 4 4 4 8 6 4 0 9 6 1 8 3 4 4 3 3 8 7 7 4 4 4 2 2 8 2 1 0 0 9 5 0 9 9 9 8 5 5 5 4 4 4 3 5 9 8 7 7 1 9 0 9 5 0 9 9 9 9 8 5 5 5 5 4 2 7 4 9 9 9 8 5 1 8 7 0 0 ...... 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 6 6 6 5 5 5 5 5 5 5 4 4 4 4 3 3 3 3 3 3 2 1 0</p><p>O</p><p>O O O O Cl O Br</p><p>MeO OMe OMe 6l</p><p>10 9 8 7 6 5 4 3 2 1 0 ppm 0 9 9 7 0 0 7 5 7 0 2 5 7 4 2 0 1 0 0 0 0 9 0 2 7 0 0 1 0 0 6 0 ...... 2 1 2 2 1 1 1 2 0 1 2 1 2 2 3 1</p><p>34 6 2 3 0 3 3 3 9 8 6 0 9 5 7 0 8 1 8 7 8 1 0 3 9 2 8 5 4 1 1 1 0 8 5 6 1 3 5 4 5 1 7 0 9 8 2 7 7 0 1 3 5 7 8 9 9 7 4 0 2 6 2 7 0 2 9 9 1 1 5 8 0 7 1 9 6 8 0 9 7 7 2 8 7 7 3 7 9 8 7 0 6 3 O3 6 9 6 6 7 ...... 3 0 6 4 7 7 0 0 3 2 1 0 1 1 9 3 3 9 6 5 3 9 1 ...... 1 2 8 2 1 0 9 8 7 6 3 3 8 8 ...... 7 5 4 3 3 2 2 2 1 0 0 7 6 6 1 1 9 7 5 4 4 3 3 2 2 2 2 2 2 0 0 7 5 2 6 7 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7 7 O7 7 7 6 6 6 5 4 4 3 O O O Cl O Br</p><p>MeO OMe OMe 6l</p><p>180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>35 O 0 3 9 6 1 5 8 8 9 9 0 4 4 9 3 0 0 3 4 4 1 6 7 1 0 7 0 7 4 0 0 2 5 4 7 0 5 7 7 5 4 9 8 O3 5 ...... 0 8 7 6 6 6 5 5 5 5 O 3 3 3 3 2 - O Cl</p><p>MeO OMe OMe 7a</p><p>8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 0 6 8 4 0 6 9 0 0 0 0 0 2 0 1 ...... </p><p>1 1 1 1 2 2 36 6 3 O O 1 3 1 5 4 2 5 0 4 7 9 6 2 0 4 1 4 4</p><p>8 4 1 9 6 5 2 8 8 2 3 6 3 8 6 5 6 O5 6 0 9 3 3 6 6 9 9 2 2 6 5 8 1 1 3 0 4 8 3 1 8 1 0 1 4 7 1 8 8 8 7 6 2 2 7 1 9 7 5 6 2 8 3 8 0 4 0 ...... 2 9 6 0 8 8 7 6 5 4 3 3 2 0 8 0</p><p>8 1 9 9 8 2 0 5 4 9 8 0 8 8 9 3 2 1 . . O...... 0 4 4 4 2 1 1 0 0 6 9 9 9 9 9 8 6 5 4 4 3 3 2 2 0 0 0 8 0 9 9 9 9 9 . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 6 C6 l 6 5 3 3 3 3 3 3 3 3 3 3 3 0</p><p>MeO OMe OMe 7a</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>37 O O</p><p>O 0 4 5 5 2 7 3 8 4 6 0 5 8 2 5 0 5 2 3 9 0 0 5 7 2 5 0 8 3 5 . . . . . 0 . . . . O . 8 7 6 6 5 Cl 4 3 Cl3 2 -</p><p>MeO OMe OMe 7b</p><p>8 7 6 5 4 3 2 1 0 ppm 4 3 5 5 6 0 1 0 0 9 0 0 0 2 ...... 1 1 0 2 2 3 6 38 O O</p><p>7 0 9 0 9 1 6 5 1 2 2 8 4 3 4 4 O 2 7 3 7 4 9 4 9 5 7 1 1 8 1 4 7 3 4 0 8 5 3 8 3 1 4 7 0 7 8 9 8 1 5 3 7 8 9 2 9 5 9 3 6 9 6 1 5 5 2 8 7 2 2 5 8 3 9 0</p><p>...... 5 2 0 O8 8 7 6 5 4 3 2 0 8 0 8 9 8 0 4 2 2 8 3 2 ...... 9 7 8 8 0 0 ...... 0 6 4 4 4 3 3 2 1 0 0 8 1 9 9 9 9 9 4 4 2 2 2 0 Cl 1 Cl 9 9 9 9 8 . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 6 6 6 3 3 3 3 3 3 3 3 3 3 0</p><p>MeO OMe OMe 7b</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 39 O O 0</p><p>6 3 6 8 3 5 1 5 6 9 O 6 6 9 2 0 4 6 2 4 9 9 5 1 9 5 1 8 9 8 0 7 2 2 8 5 0 4 4 3 3 0 9 7 5 ...... 0</p><p>7 7 7 6 6 6 5 5 5 5 4 3 3 O 1 - Br</p><p>MeO OMe OMe 7c</p><p>8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 0 7 6 1 1 4 6 1 1 0 9 9 0 0 0 0 9 0 ...... 1 0 0 1 2 2 3 402 3 O O O O 2 4 5 3 4 2 6 6 9 2 7 4 5 8 7 4 8 2</p><p>8 9 5 4 8 1 0 7 3 8 7 7 9 3 8 5 7 1 6 8 9 B9 r 3 0 9 7 1 1 9 7 6 2 8 4 2 0 7 4 6 5 6 3 3 7 8 0 9 4 0 5 . . . . . 3 7 2 2 ...... 0 3 1 9 2 1 0 8 3 9 8 4 1 9 9 9 0 9 3 3 1 ...... 5 5 5 4 2 7 6 1 1 6 4 3 3 3 3 1 1 1 0 0 0 0 7 8 6 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 M1 eO 7 7 7 O6 Me6 6 5 OMe 7c</p><p>170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm</p><p>41 O O O O</p><p>H3CO OCH3 OCH3 9</p><p>42</p>