Supporting Information

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1 Supporting Information Wiley-VCH Weinheim, Germany

2 Total Synthesis of Cassialoin, Anthrone C-Glycoside Yasuhito Koyama, Ryo Yamaguchi and Keisuke Suzuki* Department of Chemistry, Tokyo Institute of Technology and SRST-JST, , -okayama, Meguro-ku, Tokyo , Japan Experimental Section 2 Comparison of natural and synthetic cassialoin

3 Experimental Section General Methods. All reactions dealing with air- and moisture-sensitive compounds were conducted under an atmosphere of argon. Dichloromethane was distilled successively from P 2 5 and CaH 2 and stored over MS 4A. Commercially available dehydrated solvents, tetrahydrofuran (THF) and diethyl ether (Et 2 ), were used. For thin-layer chromatography (TLC) analysis, Merck precoated plates (silica gel 60 F254, Art 5715, 0.25 mm) were used. for flash column chromatography. Merck Kieselgel 60 ( mesh ASTM) was used Silica gel preparative TLC (PTLC) was performed on Merck Kieselgel 60 F 254 (Art. 7747). Melting point (mp) determinations were performed by using a Yanaco MP-S3 and MP-500V instruments and are uncorrected. 1 H-NMR (300, 400 MHz) and 13 C-NMR (75, 100 MHz) spectra were measured on a JEL JNM AL-300, JEL JNM Lamda-300, JEL JNM AL-400,and JEL JNM Lamda-400 spectrometers. Chemical shifts are expressed in parts per million downfield from internal tetramethylsilane (δ = 0). Infrared (IR) spectra were recorded on an IR Report-100 spectrometer. on a Nihonbunko RIP-1000 polarimeter. ptical rotations ([α] D ) were measured Elemental analyses were recorded on a PERKIN ELMER PE2400 Series II CHNS/ Analyzer. All compounds given below bear the same formula numbers as used in the main text. Compounds unlabeled in the main text are labeled with letters [A~G]. The nitrile oxide 3 was prepared according to: Bode, J. W.; Suzuki, K. Tetrahedron Lett. 2003, 44, The chiral 1,3-diketone 4 was prepared according to: Myers, A. G.; - 2 -

4 Tom, N. J.; Fraley, M. E.; Cohen, S. B.; Madar, D. J. J. Am. Chem. Soc. 1997, 119, DMD was prepared according to: Adam, W.; Bialas, J.; Hadjiarapoglou, L. Chem. Ber. 1991, 124, All other reagents were used as obtained from commercial sources. MM N 5 To a solution of nitrile oxide 3 (100 mg, 0.38 mmol) and 1,3-diketone 4 (139.5 mg, 0.45 mmol) in i-prh (3.6 ml) was stirred with freshly activated MS4A (380 mg) at room temperature. The suspension was warmed at 50. After stirring for 1 day, the mixture was cooled to room temperature, filtrated through a Celite pad, and the filtrate was concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (10 g, hexane, toluene, Et 2 = 4/3/3, 0.5% TFA) to give isoxazole 5 (152 mg, 72%) as white solids and the regioisomer (35.5 mg, 17%) as a yellow oil. 5: Recrystallization from hexane EtAc gave white needles: mp C; R f = 0.65 (hexane, toluene, Et 2 = 4/3/3, triple development); 1 H NMR (CDCl 3, 400 MHz, 1.2 : 1 rotamers) δ (m, 2 H), (m, 1 H), (m, 1 H), (m, 1H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), - 3 -

5 (m, 1 H), (m, 1 H), (m, 3 H), (m, 2 H), (m, 2 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 2 H), (m, 4 H), (m, 14 H); 13 C NMR (CDCl 3, 100 MHz) δ 185.2, 178.6, 169.1, 156.2, 155.9, 138.8, 138.5, 131.2, 119.6, 119.4, 115.8, 114.8, 99.1, 67.2, 64.1, 62.3, 62.1, 56.0, 47.0, 40.8, 40.6, 34.3, 33.5, 31.4, 30.1, 29.9, 26.1, 23.2, 22.1, 20.8, 15.8; IR (neat) ν 3015, 2958, 2929, 2870, 2826, 1732, 1694, 1606, 1593, 1512, 1477, 1452, 1386, 1378, 1352, 1309, 1261, 1237, 1218, 1198, 1181, 1153, 1112, 1089, 1046, 1008, 990, 956, 923, 802, 756, 667 cm 1 ; Anal. Calc d for C 31 H 41 N 8 ; C, 67.01; H, 7.44; N, Found: C, 66.77; H, 7.68; N, 2.31; [α] 23 D 0.37 (c 1.24, CHCl 3 ). MM N regioisomer regioisomer: R f = 0.54 (hexane, toluene, Et 2 = 4/3/3, triple development); 1 H NMR (CDCl 3, 400 MHz, 1.8 : 1 rotamers) δ (m, 2 H), (m, 1 H), (m, 1 H), (m, 1H), (m, 2 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 3 H), (m, 2 H), (m, 3 H), (m, 1 H), (m, 1 H), (m, 2 H), (m, 4 H), (m, 14 H); 13 C NMR (CDCl 3, 100 MHz) δ 189.2, 175.4, 168.1, 155.8, 155.6, 138.8, 130.9, 119.4, 116.5, 115.1, 114.7, - 4 -

6 99.1, 95.0, 67.0, 66.95, 66.9, 55.8, 48.4, 46.8, 44.4, 40.6, 34.3, 31.3, 26.1, 25.4, 23.2, 21.8, 20.6, 19.1, 19.0, 15.9; IR (neat) ν 2957, 2870, 2725, 1732, 1698, 1605, 1593, 1509, 1441, 1377, 1259, 1153, 1112, 1089, 1046, 1008, 986, 956, 917, 803, 734, 667 cm 1 ; MALDI-TFMS Calc d for C 31 H 41 N 8 ; Found: ; [α] 28 D 6.5 (c 1.09, CHCl 3 ). MM N aldehyde-1 To a solution of 1,3-dioxane 5 (107 mg, 0.19 mmol) in THF (1 ml) was added dropwise 3 M aq. H 2 S 4 (1 ml) at 0. The mixture was warmed to room temperature and stirred for 17 h. The resulting mixture was cooled to 0, and the reaction was quenched by the addition of sat. aq. NaHC 3, and the products were extracted with EtAc (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give aldehyde-1 (44 mg, 51%) as a yellow oil; R f = 0.60 (hexane, EtAc = 1/1); 1 H NMR (CDCl 3, 400 MHz) δ 9.86 (s, 1H), (m, 3H), (m, 2H), 4.74 (brd, 1H), 3.53 (s, 3H), (m, 2H), (m, 2H), 2.03 (d, J = 11.6 Hz, 1H), (brd, 1H), (m, 3H), 1.25 (d, J = 6.4 Hz, 3H), (m, 7H), 0.86 (d, J = Hz, - 5 -

7 3H), 0.73 (d, J = 6.8 Hz, 3H); 13 C NMR (CDCl 3, 100 MHz) δ , 186.1, 179.7, 169.1, 156.6, 154.3, 136.1, 131.5, 122.4, 121.7, 120.2, 115.5, 95.4, 75.7, 62.1, 56.2, 46.7, 40.6, 34.1, 34.0, 31.3, 29.9, 25.9, 23.0, 21.9, 20.7, 19.6, 15.8 ; IR (NaCl) ν 2957, 2930, 2870, 1732, 1697, 1597, 1507, 1469, 1450, 1388, 1369, 1353, 1310, 1260, 1200, 1156, 1088, 1024, 954, 924, 905, 844, 796, 737, 647 cm 1 ; MALDI-TFMS Calc d for C 28 H 35 N 7 Na + ; Found: ; [α] 30 D 14.4 (c 1.00, CHCl 3 ). MM HMBC N H HMBC H 2.87 H 3.28 aldehyde-1 MM N aldehyde-2 To a solution of regioisomer (162 mg, 0.29 mmol) in THF (1 ml) was added dropwise 3 M aq. H 2 S 4 (1 ml) at 0. The mixture was warmed to room temperature and stirred for 17 h. The resulting mixture was cooled to 0, and the reaction was quenched by the addition of sat. aq. NaHC 3, and the products were extracted with EtAc (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give aldehyde-2-6 -

8 (75 mg, 56%) as a oil; R f = 0.60 (hexane, EtAc = 1/1); 1 H NMR (CDCl 3, 400 MHz) δ 9.84 (s, 1H), (m, 3H), (m, 2H), (m, 1H), (m, 1 H), 3.39 (s, 3H), (m, 2H), (m, 1H), (m, 4H), (m, 3H), (m, 14H); 13 C NMR (CDCl 3, 100 MHz) δ 190.6, 190.2, 176.5, 168.0, 156.3, 154.3, 136.1, 131.7, 123.2, 121.6, 120.5, 120.0, 95.4, 56.1, 48.4, 46.7, 44.7, 40.6, 34.0, 31.5, 26.1, 26.0, 23.1, 21.9, 20.7, 20.6, 19.2, 15.9; IR (NaCl) ν 3058, 2957, 2871, 2751, 1735, 1698, 1596, 1507, 1446, 1389, 1370, 1259, 1202, 1155, 1089, 1024, 924, 905, 846, 795, 737, 703 cm 1 ; MALDI-TFMS Calc d for C 28 H 35 N 7 Na + ; Found: ; [α] 30 D 8.9 (c 1.00, CHCl 3 ). MM N A To a solution of ester 5 (2.55 g, 4.58 mmol) and DMAP (4.58 g, 4.58 mmol) in mesitylene (35 ml) and H 2 (1.5 ml) was heated at 150 for 4 h. The mixture was cooled to room temperature, and the organic/aqueous layers were separated. The aqueous phase was extracted with EtAc (x 3). The combined organic extracts were washed with successively H 2 and brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give A (1.15 g, 71%) as a colorless oil; R f = 0.20 (hexane, toluene, Et 2 = 3/3/4); 1 H NMR (CDCl 3, 400 MHz, 1 : 1 rotamers) δ (m, 2 H), - 7 -

9 (m, 1 H), 5.43 (s, 1 H), (m, 1 H), (m,1 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 3 H), (m, 1 H), (m, 1 H), (m, 2 H), (m, 1 H), (m, 1 H), (m, 4 H); 13 C NMR (CDCl 3, 100 MHz) δ 190.3, 179.7, 155.6, 155.5, 138.6, 130.8, 119.3, 116.0, 115.9, 114.8, 99.0, 95.1, 67.03, 66.98, 55.8, 46.5, 31.0, 30.6, 30.2, 25.5 ; IR (neat) ν 2960, 2924, 2850, 1693, 1593, 1508, 1475, 1444, 1379, 1319, 1259, 1236, 1205, 1151, 1111, 1088, 1045, 1003, 989, 957, 922, 895, 862, 802, 781, 752, 696, 665, 633, 606 cm 1 ; Anal. Calc d for C 20 H 23 N 6 ; C, H, 6.21; N, Found: C, 64.42; H, 6.38; N, 3.55; [α] 23 D +9.7 (c 1.10, CHCl 3 ). MM N 6 To a solution of 1,3-dioxane A (749 mg, 2.37 mmol) in THF (10 ml) was added dropwise 1 M aq. H 2 S 4 (10 ml) at 0. The mixture was warmed to room temperature and stirred for 9 h. The resulting mixture was cooled to 0, and the reaction was quenched by the addition of sat. aq. NaHC 3, and the products were extracted with EtAc (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give aldehyde 6 (532 mg, 71%) as yellow solids; R f = 0.60 (hexane, CH 2 Cl 2, Et 2 = 4/3/3 x 2); 1 H - 8 -

10 NMR (CDCl 3, 300 MHz) δ 9.85 (s, 1 H), 7.68 (d, 1 H, J = 8.4 Hz), 7.58 (d, 1 H, J = 8.4 Hz), 7.53 (d, 1 H, J = 8.4 Hz), 5.17 (dd, 1 H, J 1 = J 2 = 7.3 Hz), 5.04 (d, 1 H, J = 7.3 Hz), 3.39 (s, 3 H), 3.24 (dd, 1 H, J 1 = 4.9 Hz, J 2 = 17.4 Hz), 2.78 (dd, 1 H, J 1 = 9.7 Hz, J 2 = 17.1 Hz), (m, 2 H), (m, 1 H) 1.25 (d, 3 H, J = 6.5 Hz; 13 C NMR (CDCl 3, 75 MHz) δ 190.9, 190.3, 180.6, 156.1, 136.0, 131.3, 122.4, 122.1, 120.2, 116.1, 95.2, 56.2, 46.5, 31.1, 30.7, 20.7; IR (KBr) ν 3870, 3365, 2960, 2902, 2875, 2756, 1923, 1687, 1593, 1502, 1468, 1448, 1398, 1319, 1253, 1242, 1201, 1152, 1088, 1063, 1026, 918, 904, 839, 837, 798, 729, 627, 571, 536 cm 1 ; Anal. Calc d for C 17 H 17 N 5 ; C, ; H, 5.43; N, Found: C, 64.51; H, 5.62; N, 4.19; mp C; [α] D 0.66 (c 1.00, CHCl 3 ). MM N 8 H To a mixture of aldehyde 6 (1.98 g, 6.28 mmol) and thiazolium salt 7 (158 mg, 0.63 mmol) in t-buh (63 ml) was degassed by ultrasound. The resulting solution was warmed to 40, to which was added DBU (94 µl, 0.63 mmol). After stirring for 1 h, the reaction was stopped by the addition of H 2, and diluted with EtAc. The organic/aqueous layers were separated, and the aqueous phase was extracted with EtAc (x 3). The combined organic phase was washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, CH 2 Cl 2, EtAc = 35/20/45) to give α-ketol 8-9 -

11 (1.96 g, 99%) as pale yellow solids. Recrystallization from hexane EtAc gave pale yellow needles: mp C; R f = 0.50 (hexane, CH 2 Cl 2, Et 2 = 2/4/4); 1 H NMR (CDCl 3, 300 MHz) δ 7.73 (d, 1 H, J = 7.3 Hz), (m, 2 H), 5.28 (d, 1 H, J = 7.1 Hz), 5.24 (d, 1 H, J = 7.1 Hz), 3.50 (s, 3 H), 3.04 (dd, 1 H, J 1 = 5.6 Hz, J 2 = 17.8 Hz), 3.04 (s, 1 H, H), (m, 1 H, H3), (m, 2 H), 1.48, (t, 1 H, J = 12.7 Hz), 1.29 (d, 3 H, J = 6.7 Hz); 13 C NMR (CDCl 3, 75 MHz) δ 194.8, 171.5, 154.0, 153.1, 133.2, 131.6, 123.0, 120.5, 117.9, 113.6, 94.6, 67.5, 56.5, 37.8, 30.8, 26.2, 21.2; IR (neat) ν 3261, 2958, 2914, 2870, 1732, 1705, 1668, 1595, 1574, 1516, 1489, 1469, 1402, 1379, 1300, 1254, 1205, 1169, 1144, 1092, 1041, 1009, 987, 964, 906, 835, 777, 727, 656, 546 cm 1 ; Anal. Calc d for C 17 H 17 N 5 ; C, 64.75; H, 5.43; N, Found: C, 64.85; H, 5.50; N, 4.21; [α] D (c 1.10, CHCl 3 ); HPLC retention time (CHIRACPAC AD-H, 0.46 x 250 mm, hexane : i-prh = 87 : 13, 20 C, 254 nm) : 18.1 min (enantiomer : 21.3 min). 1.8% ne H H 3 N MM MM N H H t-bu Si t-bu TIPS

12 To a solution of glycal 9 (941 mg, 2.13 mmol) in THF (3.0 ml) was added t-buli (1.57 M in pentane, 1.1 ml, 1.73 mmol) dropwise at 78. The mixture was warmed to 0, stirred for 2 h, and then re-chilled to 78. To the resulting mixture was added dropwise a solution of α-ketol 8 (186 mg, 0.59 mmol) in THF (3.0 ml) via cannula, and the stirring was continued for 30 min at the same temperature. The reaction was stopped by the addition of sat. aq. NH 4 Cl, and the products were extracted with EtAc (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give diol 10 (337 mg, 76%) as amorphous solids. Recrystallization from MeCN H 2 gave colorless plates: mp C; R f = 0.65 (hexane, EtAc = 7/3); 1 H NMR (CDCl 3, 400 MHz) δ 7.48 (d, 1 H, J = 8.0 Hz), 7.34 (dd, 1 H, J 1 = J 2 = 8.0 Hz), 6.94 (d, 1 H, J = 8.0 Hz), 5.00 (br s, 1 H), 4.98 (d,1 H, J = 7.2 Hz), 4.95 (d,1 H, J = 7.2 Hz), 4.28, (d, 1 H, J = 6.8 Hz), 3.91 (s, 1H), (m, 4 H), 3.42 (s, 3 H), 3.35 (ddd, 1 H, J 1 = 5.6 Hz, J 2 = J 3 = 10.4 Hz), 2.91 (dd, 1 H, J 1 = 5.2 Hz, J 2 = 17.6 Hz), (m, 1 H), 2.14 (dd, 1 H, J 1 = 11.6 Hz, J 2 = 17.6 Hz), 1.98 (d, 1 H, J = 12.8 Hz), (m, 4 H), (m,

13 21 H), 0.94 (s, 9 H), (m, 9 H); 13 C NMR (CDCl 3, 100 MHz) δ 168.3, 154.8, 153.4, 152.8, 144.7, 131.0, 121.4, 114.9, 114.4, 114.1, 101.2, 94.1, 78.2, 73.0, 71.3, 68.2, 65.3, 60.4, 56.3, 38.9, 31.0, 27.4 (3C), 26.9 (3C), 26.7, 22.6, 21.4, 19.7, 18.1 (6C), 12.4 (3C); IR (neat) ν 3376, 2934, 2864, 1674, 1603, 1578, 1488, 1463, 1387, 1366, 1333, 1312, 1287, 1258, 1216, 1154, 1108, 1060, 1002, 962, 884, 867, 845, 827, 754, 681, 654 cm 1 ; Anal. Calc d for C 40 H 63 N 9 Si 2 ; C, 63.37; H, 8.38; N, Found: C, 63.15; H, 8.48; N, 1.57; [α] D (c 1.25, CHCl 3 ). Crystals of 10 suitable for X-ray analysis were obtained by vapor diffusion from acetonitrile and water. Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre (CCDC ). Copies of the data can be obtained free of charge on application to the CCDC, 12 Union Road, Cambridge CB21EZ, UK. f a x : ( ) e - m a i l : d e p o s i c c d c. c a m. a c. u k

14 MM N t-bu Si t-bu TIPS 11 To a solution of diol 10 (385 mg, 0.51 mmol) and NaH (48 mg, 1.27 mmol) in DMF (2.0 ml) was added dropwise a solution of ClCH 2 I (224.0mg, 1.27 mmol) in DMF (1.0 ml) at 0 and stirred for 2 h at room temperature. The reaction was quenched by the addition of sat. aq. NH 4 Cl at 0, diluted with EtAc and warmed to room temperature. The organic/aqueous layers were separated, and the aqueous phase was extracted with EtAc (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give methylidene 11 (328 mg, 84%) as amorphous solids; R f = 0.30 (hexane, CH 2 Cl 2, Et 2 = 2/1/1) 1 H NMR (CDCl 3, 400 MHz) δ 7.40 (dd, 1 H, J 1 = 7.6 Hz, J 2 = 8.0 Hz), 7.32 (d, 1 H, J = 7.6 Hz), 7.23 (d, 1 H, J = 8.0 Hz), 5.41 (d, 1 H, J = 6.8 Hz), 5.33 (d, 1 H, J = 6.8 Hz), 5.22 (s, 1 H), 5.06 (s, 1 H), 4.82 (s, 1 H), 4.37 (d, 1 H, J = 7.2 Hz), (m, 2 H), (m, 5 H), 2.98, (dd, 1 H, J 1 = 5.6 Hz, J 2 = 17.6 Hz), (m, 1 H), 2.25 (dd, 1 H, J 1 = 10.8 Hz, J 2 = 17.6 Hz), 1.94 (d, 1 H, J = 13.2 Hz), (m, 4 H), (m, 21 H), 0.97 (s, 9 H), 0.94 (s, 9 H); 13 C NMR (CDCl 3, 100 MHz) δ 169.7, , , 150.8, 141.4, 131.2, 121.4, 116.0, 115.2, 111.0, 101.5, 94.7, 93.3, 83.5, 76.4, 73.1, 70.9, 65.4, 56.4, 37.6, 34.7, 30.7, 27.5, 25.3, 21.5, 19.8, 18.2 (6C),

15 (3C), (3C), 12.5 (3C); IR (neat) ν 2944, 2891, 2866, 1678, 1602, 1579, 1514, 1489, 1463, 1388, 1365, 1309, 1289, 1259, 1217, 1156, 1109, 1084, 1055, 998, 879, 827, 799, 763, 681, 654 cm 1 ; Anal. Calc d for C 41 H 63 N 9 Si 2 ; C, 63.94; H, 8.25; N, Found: C, 64.05; H, 8.48; N, 1.63; mp C; [α] 26 D 1.49 x 10 3 (c 1.11, CHCl 3 ). MM NH H H t-bu Si t-bu TIPS 12 To a solution of methylidene 11 (44.0 mg, mmol) in THF (2.0 ml) was added t-buk (64 mg, 0.57 mmol) at 78. room temperature and stirred for 25 min. The reaction was warmed gradually to The reaction was stopped by the addition of sat. aq. NH 4 Cl, diluted with EtAc and warmed to room temperature. The organic/aqueous layers were separated, and the aqueous phase was extracted with EtAc (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, CH 2 Cl 2, EtAc = 35/10/35) to give imine 12 (32 mg, 76%) as orange solids; R f = 0.50 (hexane, CH 2 Cl 2, Et 2 = 2/1/1); 1 H NMR (CDCl 3, 400 MHz) δ (s, 1 H), 7.59 (d, 1 H, J = 8.0 Hz), 7.47 (dd, 1 H, J 1 = 8.0, J 2 = 8.2 Hz), 7.19 (d, 1 H, J = 8.2 Hz), 6.80 (s, 1 H), 6.59 (s, 1,H), 5.39 (d, 1 H, J = 6.6Hz),

16 (d, 1 H, J = 6.6 Hz), 4.94 (s, 1 H), 4.34 (d, 1 H, J = 6.8 Hz), 3.87 (dd, 1 H, J 1 = 4.8 Hz, J 2 = 10.0 Hz), 3.77 (dd, 1 H, J 1 = 6.8 Hz, J 2 = 10.0 Hz), 3.65 (dd, 1 H, J 1 = J 2 = 10.0 Hz), 3.55, (s, 3H), (m, 2 H), 2.28 (s, 3 H), (m, 21 H), 0.98 (s, 9 H), 0.91 (s, 9 H); 13 C NMR (CDCl 3, 100 MHz) δ 169.3, 165.1, 156.8, 154.9, 145.1, (2C), 141.3, 132.8, 121.4, 120.3, 116.1, 114.8, 114.4, 110.4, 100.5, 95.3, 73.3, 72.2, 71.2, 65.7, (3C), 26.9 (3C), 22.7, 22.1, 19.8, (6C), 12.4 (3C); IR (neat) ν 3391, 2944, 2864, 1671, 1621, 1532, 1387, 1329, 1280, 1249, 1211, 1158, 1110, 1066, 1017, 979, 894, 826, 804, 785, , 652 cm 1 ; Anal. Calc d for C 40 H 61 N 8 Si 2 ; C, 64.92; H, 8.31; N, Found: C, 65.10; H, 8.35; N, 1.63; mp C; [α] 26 D 149 (c 1.03, CHCl 3 ). MM Ns H t-bu Si t-bu TIPS 13 To a mixture of imine 12 (31.8 mg, mmol) and K 2 C 3 (59.4 mg, 0.43 mmol) in DMF (2.0 ml) was added portionwise NsCl (47.7 mg, 0.22 mmol) at 0 and stirred for 2 h. The reaction was stopped by the addition of sat. aq. NaHC 3, diluted with Et 2 and warmed to room temperature. The organic/aqueous layers were separated, and the aqueous phase was extracted with Et 2. The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The

17 crude nosylate 12 was used for the next reaction without further purification, which was dissolved in CH 2 Cl 2 (2.0 ml), added Si 2 (344 mg, Merck Kieselgel 60, mesh ASTM) at room temperature, and the stirring was continued for 14 h. The suspension was filtrated, and the filtrate was concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give ketone 13 (34 mg, 86%) as yellow solids. Recrystallization from hexane EtAc gave pale yellow needles: mp C; R f = 0.50 (hexane, EtAc = 6/4); 1 H NMR (CDCl 3, 400 MHz) δ 8.39 (d, 1 H, J = 6.4 Hz), (m, 3 H), 7.64 (s, 1 H), (m, 2 H), 7.17 (s, 1 H), 7.09 (dd,1 H, J 1 = 3.2 Hz, J 2 = 5.6 Hz), 5.24 (d,1 H, J = 6.6 Hz), 5.12, (d, 1 H, J = 6.6 Hz), 4.89 (s, 1 H), 4.26 (d, 1 H, J = 6.8 Hz), 3.81 (dd, 1 H, J 1 = 5.2 Hz, J 2 = 10.4 Hz), 3.74 (dd, 1 H, J 1 = 6.8, Hz, J 2 = 10.0 Hz), 3.65 (dd, 1 H, J 1 = 10.0 Hz, J 2 = 10.4 Hz), 3.46 (s, 3H), 3.40 (ddd, 1 H, J 1 = 5.2 Hz, J 2 = 10.4 Hz), 2.98 (d, 1 H, J = 6.4 Hz), 2.42 (s, 3 H), (m, 21 H), 0.96 (s, 9 H), 0.88 (s, 9 H); 13 C NMR (CDCl 3, 100 MHz) δ 181.4, 155.2, 154.2, 148.5, 145.1, 145.0, 144.7, (2C), 134.8, 132.9, 132.1, 132.0, 129.7, 125.4, 124.9, 124.4, 123.9, (2C), 116.9, 100.2, 95.6, 73.6, 71.9, 71.1, 65.3, 56.5, 27.4 (3C), 26.9 (3C). 22.6, 21.8, 19.8, (6C), 12.4 (3C); IR (neat) ν 3450, 2944, 2894, 2865, 1683, 1615, 1596, 1548, 1468, 1366, 1304, 1257, 1216, 1191, 1153, 1108, 1060, 1012, 982, 907, 885, 852, 813, , 654 cm 1 ; Anal. Calc d for C 46 H 63 N 13 SSi 2 ; C, 59.52; H, 7.06; N, 1.51; S, Found: C, 59.47; H, 7.31; N, 1.36; S, 3.75; [α] 26 D +9.5 (c 1.70, CHCl 3 )

18 MM Ns t-bu Si t-bu H H H Si(i-Pr) 3 15 To a solution of ketone 13 (47.0 mg, mmol) in CH 2 Cl 2 (2.0 ml) was added freshly prepared dimethyldioxirane (DMD) (~0.9 M in acetone, 0.5 ml, 0.46 mmol) 3 at 0 C and stirred for 2.5 h at room temperature. The reaction mixture was diluted with CH 2 Cl 2 and dried over MgS 4. The filtrate was concentrated in vacuo. The crude material was used for the next reaction without further purification, which was dissolved in THF (2.0 ml). After the dropwise addition of BH 3 THF (1 M, 0.5 ml, 0.5 mmol) at 0 C, the resulting mixture was stirred for 2.5 h at same temperature. The reaction was quenched by the addtion of sat. aq. NH 4 Cl, diluted with Et 2, and warmed to room temperature. The organic/aqueous layers were separated, and the aqueous phase was extracted with Et 2. The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give diol 15 (36 mg, 75%) as a yellow oil; R f = 0.50 (hexane, EtAc = 6/4); 1 H NMR (CDCl 3, 400 MHz) δ 8.43 (d, 1 H, J = 5.1 Hz), (m, 4 H), 7.49 (dd, 1 H, J 1 = J 2 = 7.9 Hz), 7.43 (d, 1 H, J = 7.6 Hz), (m, 2 H), 5.64 (s, 1 H), 5.25 (d, 1 H, J = 6.8 Hz), 5.12 (d, 1 H, J = 6.8 Hz), 3.73 (dd, 1 H, J 1 = 5.0 Hz, J 2 = 10.0 Hz), 3.64 (dd, 1 H, J 1 = J 2 = 8.5 Hz), 3.45 (dd, 1 H J = 10.0 Hz), 3.42 (s, 3 H), 3.34 (d, 1 H, J =

19 Hz, H1), 3.26 (dd, J 1 = 10.0 Hz, J 2 = 8.5 Hz, 1 H), 3.13 (dd, J 1 = 10.8 Hz, J 2 = 8.5 Hz, 1 H, H2), 3.12 (s, 1H), 3.03 (ddd, 1 H, J 1 = 5.0 Hz, J 2 = 10.0 Hz), 2.43 (s, 3 H), (m, 21 H), 0.92 (s, 9 H), 0.88 (s, 9 H); 13 C NMR (CDCl 3, 100 MHz) δ 181.1, 155.3, 148.7, 146.0, 145.5, 142.3, 134.9, 134.3, 132.0, 131.8, 130.0, 124.9, 124.6, 124.5, 123.0, 117.3, 117.2, 116.1, 95.9, 82.0, 79.6, 76.8, 75.3, 75.0, 73.3, 65.4, 56.5, 27.4 (3C), 27.0 (3C), 22.6, 22.0, 19.9, 18.5, 18.3 (6C), 13.0 (3C); IR (neat) ν 3467, 2968, 2863, 1645, 1611, 1547, 1455, 1393, 1366, 1284, 1250, 1214, 1191, 1167, 1100, 1067, 1044, 1011, 989, 934, 917, 894, 883, 840, 813, 798, 763, 683, 667, 654 cm 1 ; Anal. Calc d for C 46 H 65 N 14 SSi 2 ; C, 58.51; H, 6.94; N, 1.48; S Found: C, 58.72; H, 7.05; N, 1.29; S, 3.58; [α] 25 D 3.6 (c 1.06, CHCl 3 ). H Ns H H H t-bu Si Si(i-Pr) 3 t-bu B To a mixture of diol 15 (32.0 mg, mmol), PPTS (9.3 mg, mmol) in t-buh (2.0 ml) was refluxed for 1 h. The mixture was cooled to room temperature, to which was added by sat. aq. NaHC 3. The products were extracted with EtAc (x 3). The combined organic extracts were washed with successively H 2 and brine. The organic phase was dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to

20 give phenol B (25 mg, 81%) as a yellow oil; R f = 0.60 (hexane, EtAc = 7/3); 1 H NMR (CDCl 3, 400 MHz) δ (s, 1 H), 8.26 (d, 1 H, J = 7.6 Hz), (m, 4 H), 7.49 (dd, 1 H, J = 8.0, 8.0 Hz), 7.22 (d, 1 H, J = 7.2 Hz), 7.10 (s, 1 H), 6.93 (d, 1 H, J = 6.8 Hz), 5.63 (s, 1 H), 3.79 (dd, 1 H, J 1 = 4.8 Hz, J 2 =10.4 Hz), 3.63 (dd, 1 H, J 1 = J 2 = 8.4 Hz), 3.40 (dd, 1 H J 1 = J 2 = 10.4 Hz), 3.25 (d, 1 H J = 9.2 Hz), 3.08 (s, 1 H), 3.02 (m, 2 H),2.45 (s, 3 H), (m, 21 H), 0.93 (s, 9 H), 0.89 (s, 9 H); 13 C NMR (CDCl 3, 100 MHz) δ 186.6, 160.9, 147.6, 146.0, 145.5, 142.3, (2C), 134.3, 132.0, 131.8, 130.0, 124.9, 124.6, 124.5, 123.0, 117.3, 117.2, 116.1, 82.0, 79.6, 76.8, 75.3, 75.0, 73.3, 65.4, 27.4 (3C), 27.0 (3C), 22.6, 22.0, 19.9, 18.5 (3C), 18.3 (3C), 13.0 (3C); IR (neat) ν , 2968, 2892, 2863, 1645, 1611, 1547, 1455, 1393, 1366, 1366, 1284, 1250, 1214, 1191, 1167, 1100, 1011, 989, 934, 917, 894, 883, 840, 813, , 683, 667, 654 cm 1 ; Anal. Calc d for C 44 H 61 N 13 SSi 2 ; C, 58.71; H, 6.83; N, 1.56; S, Found: C, 58.49; H, 7.05; N, 1.48; S, 3.26; [α] 24 D +3.3 (c 0.83, CHCl 3 ). H H H H H H H H cassialoin (1) To a solution of phenol B (23.0 mg, mmol) in THF (1.0 ml) was added TBAF (1.0 M in THF, 128 µl, 0.13 mmol) at 0 C. After the reaction mixture was stirred for 1 day, quenching with TFA (0.1 ml) and concentration in vacuo gave crude

21 material. The crude material was dissolved in MeH (2 ml), to which was added Dowex-50WX8-400 (420 mg) and CaC 3 (140 mg), and the stirring was continued for 1 day at room temperature. The mixture was filtrated through a Celite pad and concentrated in vacuo. The crude material was purified by reverse phase preparative thin layer chromatography [MeH, H 2 (65 : 35), 0.1% TFA] to give cassialoin (1) (5.7 mg, 53%) as yellow solids. Recrystallization from hexane EtAc gave pale yellow needles: mp C; R f = 0.50 (CHCl 3, MeH =5/1); 1 H NMR (400 MHz CD 3 D) δ 7.57 (dd, 1H, J = 8.4, 7.6 Hz), 7.38 (d, 1H, J = 7.6 Hz), 7.32 (s, 1H), 6.92 (d, 1H, J = 8.4 Hz), 6.76 (s, 1H), 3.57 (dd, 1H, J = 12, 2.4 Hz), 3.35 (dd, 1H, J = 12, 6.0 Hz), 3.25 (d, 1H, J = 9.2 Hz), 3.24 (t, 1H, J = 8.8 Hz), 2.97 (dd, 1H, J = 9.2, 8.8 Hz), 2.94 (ddd, 1H, J = 9.6, 6.0, 2.4 Hz), 2.81 (dd, 1H, J = 9.6, 8.8 Hz), 2.40 (s, 3H); 13 C NMR (100 MHz CD 3 D) δ 194.4, (2C), 149.2, 148.9, 146.7, 136.3, 119.2, 118.9, 118.1, 118.0, 117.7, 115.1, 85.3, 81.7, 79.6, 76.7, 73.0, 71.7, 63.3, 30.8; IR (neat) υ 3556, 2957, 2924, 2854, 1730, 1637, 1603, , 1377, 1285, 1251, 1213, 1165, 1128, 1079, 834, 757, 721 cm 1 ; MALDI-TFMS Calc d for C 21 H 22 Na Found ; [α] 23 D 43 (c 0.10, EtH). MM N MM N H H + H H Si Si(i-Pr) t-bu 3 t-bu 10 Si Si(i-Pr) t-bu 3 t-bu C

22 To a solution of glycal 9 (1.40 g, 3.16 mmol) in THF (4.0 ml) was added t-buli (1.57 M solution in pentane, 1.68 ml, 2.63 mmol) dropwise at 78. was warmed to 0, stirred for 2 h, and then re-chilled to 78. The mixture To the resulting mixture was added dropwise a solution of α-ketol 16 (276.5 mg, 0.88 mmol) in THF (5.0 ml) via cannula, and the stirring was continued for 30 min at the same temperature. The reaction was stopped by the addition of sat. aq. NH 4 Cl, and the products were extracted with EtAc (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give an inseparable mixture of diol 10 and C (664 mg, 82%, 1 : 1) as amorphous solids; R f = 0.65 (hexane, EtAc = 7/3); 1 H NMR (CDCl 3, 400 MHz) δ (m, 1 H), (m, 1 H), (m, 1 H), (m, 2 H), 4.98 (s,1 H), 4.95 (d,1 H, J = 7.2 Hz), , (m, 1 H), 3.85 (br s, 1 H), (m, 3 H), 3.42 (s, 3 H), (m, 2 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 3 H), (m, 21 H), (m, 18 H); IR (neat) ν 3378, 2930, 2866, 1674, 1600, 1578, 1488, 1461, 1387, 1366, 1333, 1312, 1287, 1258, 1216, 1154, 1108, 1060, 1002, 962, 880, 867, 842, 831, 751, 678, 650 cm

23 MM N MM N + Si Si(i-Pr) t-bu 3 t-bu 11 Si Si(i-Pr) t-bu 3 t-bu D To a solution of diol 10 and C (100.0 mg, 0.10 mmol) and NaH (10.2 mg, 0.27 mmol) in DMF (1.0 ml) was added dropwise a solution of ClCH 2 I (47.0 mg, 0.30 mmol) in DMF (0.1 ml) at 0 and stirred for 3 h at room temperature. The reaction was quenched by the addition of sat. aq. NH 4 Cl at 0, diluted with EtAc and warmed to room temperature. The organic/aqueous layers were separated, and the aqueous phase was extracted with EtAc (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give an inseparable mixture of methylidene 11 and D (92.0 mg. 91%, 1 : 1) as amorphous solids; R f = 0.30 (hexane, CH 2 Cl 2, Et 2 = 2/1/1); 1 H NMR (CDCl 3, 400 MHz) δ (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), 5.23 (s, 0.5 H), 5.22 (s, 0.5 H), 5.06, (s, 0.5 H), 5.01 (s, 0.5 H), 4.85 (s, 0.5 H), 4.82 (s, 0.5 H), (m,1 H), (m, 1 H), (m, 1H), (m,5 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 4 H), (m, 21 H), (m, 18 H); IR (neat) ν 2944, 2891, 2866, 1678, 1602, 1579, 1514, 1489, 1463, 1388, 1365, 1309, 1289, 1259, 1217, 1156, 1109, 1084, 1055, 998, 879, 827, 799, 763, 681, 654 cm

24 MM NH H MM NH H H + H Si Si(i-Pr) t-bu 3 t-bu 12 Si Si(i-Pr) t-bu 3 t-bu E To a solution of methylidene 11 and D (92 mg, mmol) in THF (2.0 ml) was added t-buk (134 mg, 1.20 mmol) at 78. The reaction was warmed gradually to room temperature and stirred for 25 min. The reaction was stopped by the addition of sat. aq. NH 4 Cl, diluted with Et 2 and warmed to room temperature. The organic/aqueous layers were separated, and the aqueous phase was extracted with Et 2 (x 3). The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, CH 2 Cl 2, EtAc = 35/10/35) to give an inseparable mixture of imine 12 and E (68 mg, 77%, 1 : 1) as orange solids; R f = 0.50 (hexane, CH 2 Cl 2, Et 2 = 2/1/1); 1 H NMR (CDCl 3, 400 MHz) δ (s, 1 H), (m, 2 H), (m, 1 H), 6.86 (s, 1 H), 6.84 (s, 1 H), (m, 3 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 4 H), 2.28 (s, 3 H), (m, 39 H); IR (neat) ν 3391, 2944, 2864, 1671, 1621, 1532, 1387, 1329, 1280, 1249, 1211, 1158, 1110, 1066, 1017, 979, 894, 826, 804, 785, , 652 cm

25 MM Ns MM Ns H + H Si Si(i-Pr) t-bu 3 t-bu 13 Si Si(i-Pr) t-bu 3 t-bu F To a mixture of imine 12 and E (50.2 mg, mmol) and K 2 C 3 (93.2 mg, 0.68 mmol) in DMF (2.0 ml) was added portionwise NsCl (74.9 mg, 0.34 mmol) at 0 and stirred for 2 h at room temperature. The reaction was stopped by the addition of sat. aq. NaHC 3, diluted with Et 2 and warmed to room temperature. The organic/aqueous layers were separated, and the aqueous phase was extracted with Et 2. The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude nosylate was used for the next reaction without further purification, which was dissolved in CH 2 Cl 2 (2.0 ml), to which was added Si 2 (540 mg, Merck Kieselgel 60, mesh ASTM) at room temperature, and the stirring was continued for 14 h. The suspension was filtrated, and the filtrate was concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give an inseparable mixture of ketone 13 and F (50.1 mg, 80%, 1 : 1) as yellow solids; R f = 0.50 (hexane, EtAc = 6/4); 1 H NMR (CDCl 3, 400 MHz) δ (m, 1 H), (m, 3 H), 7.64 (s, 0.5 H), 7.61 (0.5 H), (m, 2 H), (m, 2 H), (m,1 H), , (m, 1 H), 4.93 (s, 0.5 H), 4.89 (s, 0.5 H), (m, 1 H), (m, 2 H), (m, 1H), 3.49 (s, 1.5 H), 3.47 (s, 1.5 H), (m, 1 H), 2.98 (d, 1 H, J = 6.4 Hz), 2.42 (s, 3 H), (m, 39 H); IR (neat) ν 3450, 2944, 2894, 2865,

26 1683, 1615, 1596, 1548, 1468, 1366, 1304, 1257, 1216, 1191, 1153, 1108, 1060, 1012, 982, 907, 885, 852, 813, , 654 cm 1. MM Ns MM Ns t-bu Si t-bu H 10 H H Si(i-Pr) 3 15 (!-H) + t-bu Si t-bu H 10 H H Si(i-Pr) 3 17 ("-H) To a solution of ketone 13 and F (48.0 mg, mmol) in CH 2 Cl 2 (2.0 ml) was added freshly prepared dimethyldioxirane (DMD) (~0.9 M in acetone, 0.56 ml, 0.5 mmol) 3 at 0 C and stirred for 2.5 h. The reaction mixture was diluted with CH 2 Cl 2, and dried over MgS 4. The filtrate was concentrated in vacuo. The crude material was used for the next reaction without further purification, which was dissolved in THF (ml). After dropwise addition of BH 3 THF (1 M in THF, 0.5 ml, 0.5 mmol) at 0 C, the resulting mixture was stirred for 2.5 h at the same temperature. The reaction was stopped by the addition of sat. aq. NH 4 Cl, diluted with Et 2, and warmed to room temperature. The organic/aqueous layers were separated, and the aqueous phase was extracted with Et 2. The combined organic extracts were washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give diol 15 (19.0 mg, 39%) and 17 (15.1 mg, 35%) as a yellow oil. 17: R f = 0.45 (hexane, EtAc = 6/4); 1 H NMR (CDCl 3, 400 MHz) δ 8.33 (d, 1 H, J =

27 7.6 Hz), (m, 3 H), 7.79 (d, 1 H, J = 2.4 Hz), 7.73 (m, 1 H), 7.47 (dd, 1 H, J 1 = J 2 = 8.0 Hz), 7.18 (m, 1 H), (m, 1 H), 5.48 (s, 1 H), 5.20 (d, 1 H, J = 6.4 Hz), 5.16 (d, 1 H, J = 6.4 Hz), 3.64 (dd, J 1 = 4.8 Hz, J 2 = 8.5 Hz, 1 H), 3.63 (dd, J 1 = J 2 = 8.5 Hz, 1 H), 3.51 (s, 3 H), 3.45 (dd, J 1 = J 2 = 8.5 Hz, 1 H), 3.33 (d, J = 8.5 Hz, 1 H, H1), 3.29 (dd, J 1 = J 2 = 8.5 Hz, 1 H), 3.20 (s, 1H,), 3.13 (dd, J 1 = J 2 = 8.5 Hz, 1 H, H2), 3.00 (ddd, 1 H, J 1 = 4.8 Hz, J 2 = J 3 =8.5 Hz), 2.45 (s, 3 H), (m, 21 H), 0.93 (s, 9 H), 0.87 (s, 9 H); 13 C NMR (CDCl 3, 100 MHz) δ 186.1, 154.7, 148.7, 148.6, 145.9, 144.9, 142.5, 134.7, 132.6, 132.2, 132.0, 129.8, 126.6, 125.8, 125.2, 124.6, 124.4, 118.5, 118.1, 82.0, 79.5, 76.8, 75.3, 75.0, 74.9, 73.3, 65.4, 27.4 (3C), 27.0 (3C), 22.6, 22.0, 19.9, 18.5, 18.3 (6C), 13.0 (3C); IR (neat) ν 3467, 2968, 2863, 1645, 1611, 1547, 1455, 1393, 1366, 1284, 1250, 1214, 1191, 1167, 1100, 1067, 1044, 1011, 989, 934, 917, 894, 883, 840, 813, 798, 763, 683, 667, 654 cm 1 ; Anal. Calc d for C 46 H 65 N 14 SSi 2 ; C, 58.51; H, 6.94; N, 1.48; S Found: C, 58.27; H, 6.69; N, 1.27; S, 3.56; [α] 22 D 63.5 (c 0.80, CHCl 3 ). H Ns t-bu Si t-bu H 10 H H Si(i-Pr) 3 G To a mixture of diol 17 (15.1 mg, mmol), PPTS (24.0 mg, mmol) in t-buh (2.0 ml) was refluxed for 7 h. The mixture was cooled to room temperature,

28 to which was added sat. aq. NaHC 3. The products were extracted with EtAc (x 3). The combined organic extracts were washed with successively H 2 and brine. The organic phase was dried over Na 2 S 4, and concentrated in vacuo. The crude material was purified by flash column chromatography on silica gel (hexane, EtAc = 6/4) to give phenol G (13.0 mg, 90%) as a yellow oil; R f = 0.60 (hexane, EtAc = 7/3); 1 H NMR (CDCl 3, 400 MHz) δ (s, 1 H), 8.21 (d, 1 H, J = 8.0 Hz), (m, 3 H), 7.47 (dd, 1 H, J 1 = J 2 = 7.6 Hz), 7.41 (d, 1 H, J = 7.6 Hz), 7.17 (s, 1 H), 6.88 (d, 1 H, J = 8.0 Hz), 5.50 (s, 1 H), (m, 3 H, J 1 = 4.8 Hz), 3.51 (dd, 1 H J 1 = J 2 = 10.0 Hz), 3.30 (d, 1 H J = 9.2 Hz), 3.21 (d, 1 H, J = 9.6 Hz), 3.11 (s, 1 H), 3.06 (dd, 1 H, J 1 = 9.6 Hz), 2.98 (ddd, 1 H, J 1 = 4.8 Hz, J 2 = J 3 = 9.6 Hz), 2.48 (s, 3 H), (m, 21 H), 1.00 (s, 9 H), 0.85 (s, 9 H); 13 C NMR (CDCl 3, 100 MHz) δ 186.6, 160.3, 146.9, 145.2, 145.1, 144.5, 144.3, 135.1, 135.0, 132.0, 131.8, 130.0, 124.9, 124.6, 124.5, 123.1, 117.5, 117.0, 115.2, 82.0, 79.6, 76.8, 75.3, 75.0, 73.3, 65.3, 27.4 (3C), 27.0 (3C), 22.6, 22.0, 19.9, 18.5 (3C), 18.3 (3C), 13.0 (3C); IR (neat) ν , 2968, 2892, 2863, 1645, 1611, 1547, 1455, 1393, 1366, 1366, 1284, 1250, 1214, 1191, 1167, 1100, 1011, 989, 934, 917, 894, 883, 840, 813, , 683, 667, 654 cm 1 ; Anal. Calc d for C 44 H 61 N 13 SSi 2 ; C, 58.71; H, 6.83; N, 1.56; S Found: C, 58.49; H, 7.04; N, 1.39; S, 3.70; [α] 24 D 38.8 (c 0.75, CHCl 3 )

29 H H H H H 10 H H H C10-epimer (1') To a solution of phenol G (19.5 mg, mmol) in THF (1.0 ml) was added TBAF (1.0 M in THF, 108 µl, 0.11 mmol) at 0 C. After the reaction mixture was stirred for 8.5 h, quenching by TFA (0.1 ml) and concentration in vacuo gave crude material. The crude material was dissolved in MeH (2 ml), to which was added Dowex-50WX8-400 (420 mg) and CaC 3 (140 mg), and the stirring was continued for 1 day at room temperature. The mixture was filtrated through a Celite pad and concentrated in vacuo. The crude material was purified by reverse phase preparative thin layer chromatography [MeH, H 2 (65 : 35), 0.1% TFA] to give C10-epimer (1 ) (5.1 mg, 56%) as a yellow oil; R f = 0.50 (CHCl 3, MeH = 5); 1 H NMR (CD 3 D, 400 MHz) δ 7.56 (dd, 1 H, J 1 = 8.0 Hz), 7.46 (d, 1 H, J = 6.4 Hz), 7.33 (s, 1 H), 6.91 (d, 1 H, J = 8.0 Hz), 6.77 (s, 1 H), 3.57 (dd, 1 H, J 1 = 2.4 Hz, J 2 = 12.0 Hz), (m, 4 H), (m, 2 H), 2.82 (dd, 1 H, J 1 = 9.2 Hz), 2.42 (s, 3 H); 13 C NMR (CD 3 D, 100 MHz) δ 194.4, (2C), 149.2, 148.9, 146.7, 136.3, 119.2, 118.9, 118.1, 118.0, 117.7, 115.1, 85.3, 81.7, 79.6, 76.7, 73.0, 71.7, 63.3, 30.8; IR (neat) ν 3556, 2957, 2924, 2854, 1730, 1637, 1603, , 1377, 1285, 1251, 1213, 1165, 1128, 1079, 834, 757, 721 cm 1 ; MALDI-TFMS Calc d for C 21 H 22 Na Found ; [α] 26 D 1.7 (c 0.24, EtH)

30 Comparison of natural and synthetic cassialoin NMR data (in CD 3 D) comparison of natural and synthetic cassialoin 1 H-NMR Natural (400 Hz) Synthetic (400 Hz) 7.57 (dd, 1H, J = 8.4, 7.6 Hz) 7.57 (dd, 1H, J = 8.4, 7.6 Hz) 7.38 (d, 1H, J = 7.6 Hz) 7.38 (d, 1H, J = 7.6 Hz) 7.32 (s, 1H) 7.32 (s, 1H) 6.92 (d, 1H, J = 8.4 Hz) 6.92 (d, 1H, J = 8.4 Hz) 6.76 (s, 1H) 6.76 (s, 1H) 3.57 (dd, 1H, J = 12, 2.4 Hz) 3.57 (dd, 1H, J = 12, 2.4 Hz) 3.35 (dd, 1H, J = 12, 6.0 Hz) 3.35 (dd, 1H, J = 12, 6.0 Hz) 3.25 (d, 1H, J = 9.2 Hz) 3.25 (d, 1H, J = 9.2 Hz) 3.24 (t, 1H, J = 8.8 Hz) 3.24 (t, 1H, J = 8.8 Hz) 2.97 (dd, 1H, J = 9.2, 8.8 Hz) 2.97 (dd, 1H, J = 9.2, 8.8 Hz) 2.94 (ddd, 1H, J = 9.6, 6.0, 2.4 Hz) 2.94 (ddd, 1H, J = 9.6, 6.0, 2.4 Hz) 2.81 (dd, 1H, J = 9.6, 8.8 Hz) 2.81 (dd, 1H, J = 9.6, 8.8 Hz) 2.40 (s, 3H) 2.40 (s, 3H)

31 13 C-NMR Natural (100 Hz) Synthetic (100 Hz) (2C) (2C)

32 [α] D for Natural and Synthetic cassialoin Natural cassialoin Synthetic cassialoin [α] D [α] D (c 1.05, EtH) [α] D (c 0.10, EtH)

33 HPLC data for natural and synthetic cassialoin a Natural cassialoin (authentic specimen): Synthetic cassialoin 1: C10 epimer 1 : a Experimental condition: Column: CHIRALPAK AD-H (4.6 mm x 25 cm), Eluent: hexane/2-propanol = 70/30 Detector wavelength: 254 nm, Flow rate: 1.0 ml/min, Temperature: 20 C

34 1 H-NMR (400 MHz, CD 3 D) of natural cassialoin 1 H-NMR (400 MHz, CD 3 D) of synthetic cassialoin 1 H-NMR (400 MHz, CD 3 D) of synthetic C10-epimer

35 13 C-NMR (100 MHz, CD 3 D) of natural cassialoin 13 C-NMR (100 MHz, CD 3 D) of synthetic cassialoin 13 C-NMR (100 MHz, CD 3 D) of synthetic C10-epimer

36 IR of natural cassialoin IR (Nujol) υ: 3350, 1640, 1610, 1600, 1580 cm 1 IR of synthetic cassialoin IR of synthetic C10-epimer

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