3.3.5. General Procedure: Synthesis of Compounds 9–22
To a solution of 1 (1 equiv, 50 mg, 0.149 mmol) in 10 mL of methanol was added the corresponding amine (5 equiv). The reaction mixture was stirred at room temperature until the starting material disappeared (with aniline and 4-methoxyaniline, the reaction mixture was heated to 50 °C). The solvent was removed under reduced pressure. The resulting residue was purified on a silica gel column using dichloromethane–methanol as eluent, and then a C18 reversed phase silica gel column using methanol–water as eluent to obtain the corresponding products.
6-(Methylamino)-6-demethoxybostrycin (9). Yield 53.6%; red solid (MeOH); mp: 266–267 °C; IR (KBr): νmax = 3532, 3457, 3389, 3319, 2973, 2928, 2843, 2808, 1584, 1517, 1418 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.47 (s, 1H, 9-OH), 12.32 (s, 1H, 10-OH), 8.02 (q, J = 5.0 Hz, 1H, NH), 5.57 (s, 1H, 7-H), 5.14 (d, J = 4.8 Hz, 1H, 1-OH), 4.96 (d, J = 4.6 Hz, 1H, 2-OH), 4.75 (t, J = 4.8 Hz, 1H, 1-H), 4.50 (s, 1H, 3-OH), 3.52 (t, J = 4.6 Hz, 1H, 2-H), 2.83 (d, J = 5.0 Hz, 3H, NHCH3), 2.72 (d, J = 17.8 Hz, 1H, 4-Hb), 2.64 (d, J = 17.8 Hz, 1H, 4-Ha), 1.23 (s, 3H, 3-CH3); 13C NMR (125 MHz, DMSO-d6): δ 185.83 (C-8), 183.20 (C-5), 155.33 and 155.22 (C-9 and C-10), 150.44 (C-6), 139.49 (C-9a), 132.93 (C-4a), 109.60 (C-10a), 107.92 (C-8a), 98.58 (C-7), 76.38 (C-2), 69.36 (C-3), 68.56 (C-1), 34.75 (C-4), 29.08 (NHCH3), 25.68 (3-CH3); EIMS m/z 335 [M]+ (46), 317 (14), 288 (31), 261 (65), 246 (11), 233 (100), 218 (23), 204 (8).
6-(n-Propylamino)-6-demethoxybostrycin (10). Yield 50.2%; red solid (MeOH); mp: 210–211 °C; IR (KBr): νmax = 3555, 3439, 3385, 3280, 3085, 2966, 2934, 2907, 2876, 1581, 1510, 1433 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.51 (s, 1H, 9-OH), 12.33 (s, 1H, 10-OH), 7.97 (br t, 1H, NH), 5.67 (s, 1H, 7-H), 5.14 (d, J = 4.4 Hz, 1H, 1-OH), 4.95 (d, J = 4.2 Hz, 1H, 2-OH), 4.74 (t, J = 4.4 Hz, 1H, 1-H), 4.49 (s, 1H, 3-OH), 3.51 (t, J = 4.2 Hz, 1H, 2-H), 3.18 (q, J = 7.3 Hz, 2H, 1′-CH2), 2.72 (d, J = 17.8 Hz, 1H, 4-Hb), 2.64 (d, J = 17.8 Hz, 1H, 4-Ha), 1.60 (sextet, J = 7.4 Hz, 2H, 2′-CH2), 1.22 (s, 3H, 3-CH3), 0.91 (t, J = 7.5 Hz, 3H, 3′-CH3); 13C NMR (125 MHz, DMSO-d6): δ 185.87 (C-8), 183.30 (C-5), 155.27 and 155.25 (C-9 and C-10), 149.57 (C-6), 139.53 (C-9a), 132.89 (C-4a), 109.63 (C-10a), 107.83 (C-8a), 98.56 (C-7), 76.38 (C-2), 69.36 (C-3), 68.57 (C-1), 43.72 (C-1′), 34.74 (C-4), 25.67 (3-CH3), 20.67 (C-2′), 11.26 (C-3′); EIMS m/z 363 [M]+ (43), 345 (13), 316 (53), 302 (16), 289 (83), 261 (61), 232 (100), 218 (30).
6-(n-Butylamino)-6-demethoxybostrycin (11). Yield 48.5%; red solid (MeOH); mp: 236–237 °C; IR (KBr): νmax = 3559, 3427, 3283, 3090, 2956, 2932, 2872, 1579, 1510, 1443 cm–1; 1H NMR (500 MHz, DMSO-d6): δ 14.47 (s, 1H, 9-OH), 12.32 (s, 1H, 10-OH), 7.89 (t, J = 5.4 Hz, 1H, NH), 5.65 (s, 1H, 7-H), 5.07 (d, J = 4.7 Hz, 1H, 1-OH), 4.88 (d, J = 4.8 Hz, 1H, 2-OH), 4.75 (t, J = 4.7 Hz, 1H, 1-H), 4.43 (s, 1H, 3-OH), 3.52 (t, J = 4.8 Hz, 1H, 2-H), 3.21 (dt, J = 5.4, 7.5 Hz, 2H, 1′-CH2), 2.73 (d, J = 17.8 Hz, 1H, 4-Hb), 2.65 (d, J = 17.8 Hz, 1H, 4-Ha), 1.57 (pentet, J = 7.5 Hz, 2H, 2′-CH2), 1.34 (sextet, J = 7.3 Hz, 2H, 3′-CH2), 1.23 (s, 3H, 3-CH3), 0.91 (t, J = 7.5 Hz, 3H, 4′-CH3); 13C NMR (125 MHz, DMSO-d6): δ 185.82 (C-8), 183.26 (C-5), 155.29 (C-9 and C-10), 149.53 (C-6), 139.52 (C-9a), 132.91 (C-4a), 109.62 (C-10a), 107.83 (C-8a), 98.50 (C-7), 76.38 (C-2), 69.36 (C-3), 68.58 (C-1), 41.80 (C-1′), 34.75 (C-4), 29.34 (C-2′), 25.67 (3-CH3), 19.60 (C-3′), 13.56 (C-4′); EIMS m/z 377 [M]+ (43), 359 (18), 341 (21), 303 (98), 275 (70), 260 (24), 232 (100), 218 (35).
6-(n-Hexylamino)-6-demethoxybostrycin (12). Yield 45%; red solid (MeOH); mp: 203–204 °C; IR (KBr): νmax = 3557, 3384, 3285, 3089, 2955, 2929, 2859, 1578, 1512, 1436 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.47 (s, 1H, 9-OH), 12.33 (s, 1H, 10-OH), 7.91 (t, J = 6.1 Hz, 1H, NH), 5.65 (s, 1H, 7-H), 5.08 (d, J = 4.8 Hz, 1H, 1-OH), 4.89 (d, J = 4.6 Hz, 1H, 3-OH), 4.75 (t, J = 4.8 Hz, 1H, 1-H), 4.44 (s, 1H, 3-OH), 3.52 (t, J = 4.6 Hz, 1H, 2-H), 3.21 (dt, J = 6.1, 7.0 Hz, 2H, 1′-CH2), 2.73 (d, J = 17.8 Hz, 1H, 4-Hb), 2.65 (d, J = 17.8 Hz, 1H, 4-Ha), 1.58 (pentet, J = 7.0 Hz, 2H, 2′-CH2), 1.37–1.26 (m, 6H, 3′, 4′ and 5′-CH2), 1.23 (s, 3H, 3-CH3), 0.87 (t, J = 7.1 Hz, 3H, 6′-CH3); 13C NMR (100 MHz, DMSO-d6): δ 185.90 (C-8), 183.36 (C-5), 155.31 and 155.27 (C-9 and C-10), 149.55 (C-6), 139.58 (C-9a), 132.92 (C-4a), 109.67 (C-10a), 107.87 (C-8a), 98.54 (C-7), 76.41 (C-2), 69.39 (C-3), 68.60 (C-1), 42.11 (C-1′), 34.77 (C-4), 30.87 (C-2′), 27.23 and 26.07 (C-3′ and C-4′), 25.70 (3-CH3), 21.97 (C-5′), 13.82 (C-6′); EIMS m/z 405 [M]+ (29), 387 (10), 358 (39), 331 (85), 303 (67), 382 (30), 323 (100), 218 (32).
6-(2′-Hydroxyethylamino)-6-demethoxybostrycin (13). Yield 30%; red solid (MeOH); mp: 202–203 °C; IR (KBr): νmax = 3374, 2968, 2924, 2898, 2857, 1587, 1518, 1439, 1402 cm–1; 1H NMR (500 MHz, DMSO-d6): δ 14.45 (s, 1H, 9-OH), 12.31 (s, 1H, 10-OH), 7.70 (t, J = 6.0 Hz, 1H, NH), 5.73 (s, 1H, 7-H), 5.12 (d, J = 4.6 Hz, 1H, 1-OH), 4.92 (d, J = 4.4 Hz, 1H, 2-OH), 4.89 (t, J = 6.0 Hz, 1H, 2′-OH), 4.74 (t, J = 4.6 Hz, 1H, 1-H), 4.46 (s, 1H, 3-OH), 3.61 (q, J = 6.0 Hz, 2H, 2′-CH2), 3.51 (t, J = 4.4 Hz, 1H, 2-H), 3.29 (q, J = 6.0 Hz, 2H, 1′-CH2), 2.72 (d, J = 17.8 Hz, 1H, 4-Hb), 2.65 (d, J = 17.8 Hz, 1H, 4-Ha), 1.22 (s, 3H, 3-CH3); 13C NMR (125 MHz, DMSO-d6): δ 185.92 (C-8), 183.03 (C-5), 155.40 (C-9 and C-10), 149.79 (C-6), 139.56 (C-9a), 133.08 (C-4a), 109.55 (C-10a), 107.81 (C-8a), 98.95 (C-7), 76.38 (C-2), 69.36 (C-3), 68.58 (C-1), 58.41 (C-2′), 44.81 (C-1′), 34.78 (C-4), 25.68 (3-CH3); EIMS m/z 365 [M]+ (8), 349 (24), 327 (13), 314 (100), 298 (39), 282 (73), 276 (16), 232 (24).
6-[(2″-Hydroxyethoxy)ethylamino]-6-demethoxybostrycin (14). Yield 40.2%; red solid (MeOH); mp: 112–113 °C; IR (KBr): νmax = 3376, 2973, 2922, 2872, 1584, 1516, 1439, 1373 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.38 (s, 1H, 9-OH), 12.30 (s, 1H, 10-OH), 7.68 (t, J = 5.6 Hz, 1H, NH), 5.74 (s, 1H, 7-H), 5.14 (d, J = 4.8 Hz, 1H, 1-OH), 4.94 (d, J = 4.6 Hz, 1H, 2-OH), 4.75 (t, J = 4.8 Hz, 1H, 1-H), 4.68 (t, J = 5.2 Hz, 1H, 2″-OH), 4.50 (s, 1H, 3-OH), 3.65 (t, J = 5.6 Hz, 2H, 1″-CH2), 3.58–3.50 (m, 5H, 2-H, 2′-CH2 and 2″-CH2), 3.40 (q, J = 5.6 Hz, 2H, 1′-CH2), 2.74 (d, J = 17.8 Hz, 1H, 4-Hb), 2.65 (d, J = 17.8 Hz, 1H, 4-Ha), 1.24 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 186.59 (C-8), 183.63 (C-5), 155.87 and 155.84 (C-9 and C-10), 150.12 (C-6), 140.09 (C-9a), 133.61 (C-4a), 110.09 (C-10a), 108.34 (C-8a), 99.65 (C-7), 76.92 (C-2), 72.60 (C-2′), 69.96 (C-3), 69.12 (C-1), 67.93 (C-1″), 60.65 (C-2″), 42.65 (C-1′), 35.29 (C-4), 26.16 (3-CH3); EIMS m/z 409 [M]+ (2), 389 (24), 373 (4), 357 (5), 327 (9), 314 (100), 300 (27), 282 (31).
6-(Phenylamino)-6-demethoxybostrycin (15). Yield 60.4%; red solid (MeOH); mp: 226–227 °C; IR (KBr): νmax = 3576, 3560, 3409, 3248, 3037, 2968, 2919, 2901, 2850, 1587, 1572, 1521, 1444 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 14.16 (s, 1H, 9-OH), 12.47 (s, 1H, 10-OH), 9.50 (br s, 1H, NH), 7.51–7.28 (m, 5H, Ar-H), 6.07 (s, 1H, 7-H), 5.13 (br s, 1H, 1-OH), 4.91 (d, J = 4.5 Hz, 1H, 2-OH), 4.81 (br t, 1H, 1-H), 4.45 (s, 1H, 3-OH), 3.57 (t, J = 4.6 Hz, 1H, 2-H), 2.80 (d, J = 17.9 Hz, 1H, 4-Hb), 2.72 (d, J = 17.9 Hz, 1H, 4-Ha), 1.28 (s, 3H, 3-CH3); 13C NMR (125 MHz, DMSO-d6): δ 186.46 (C-8), 182.83 (C-5), 155.87 and 155.73 (C-9 and C-10), 147.33 (C-6), 139.49 (C-9a), 137.65 (C-1′), 133.97 (C-4a), 129.27 (C-3′ and C-5′), 125.63 (C-4′), 123.91 (C-2′ and C-6′), 109.63 (C-10a), 107.84 (C-8a), 101.33 (C-7), 76.40 (C-2), 69.36 (C-3), 68.51 (C-1), 34.86 (C-4), 25.68 (3-CH3); EIMS m/z 397 [M]+ (20), 377 (45), 361 (28), 345 (27), 324 (53), 295 (100), 280 (14), 266 (4).
6-(p-Methoxyphenylamino)-6-demethoxybostrycin (16). Yield 50.1%; red solid (MeOH); mp: 202–203 °C; IR (KBr): νmax = 3379, 3260, 3032, 2964, 2921, 2838, 1585, 1522, 1440, 1418 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.22 (s, 1H, 9-OH), 12.43 (s, 1H, 10-OH), 9.43 (br s, 1H, NH), 7.33 (d, J = 8.6 Hz, 2H, Ar-H), 7.05 (br d, J = 8.6 Hz, 2H, Ar-H), 5.88 (s, 1H, 7-H), 5.11 (br s, 1H, 1-OH), 4.91 (br s, 1H, 2-OH), 4.79 (br t, 1H, 1-H), 4.46 (s, 1H, 3-OH), 3.81 (s, 3H, 4′-OMe), 3.56 (br t, 1H, 2-H), 2.79 (d, J = 17.9 Hz, 1H, 4-Hb), 2.70 (d, J = 17.9 Hz, 1H, 4-Ha), 1.27 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 186.55 (C-8), 183.34 (C-5), 157.25 (C-4′), 155.58 and 155.51 (C-9 and C-10), 148.02 (C-6), 139.60 (C-9a), 133.67 (C-4a), 130.22 (C-1′), 125.83 (C-2′ and C-6′), 114.58 (C-3′ and C-5′), 109.75 (C-10a), 107.95 (C-8a), 100.50 (C-7), 76.47 (C-2), 69.45 (C-3), 68.58 (C-1), 55.34 (4′-OMe), 34.89 (C-4), 25.76 (3-CH3); EIMS m/z 427 [M]+ (29), 407 (74), 392 (53), 360 (44), 325 (41), 310 (33), 284 (18), 263 (100).
6-(Benzylamino)-6-demethoxybostrycin (17). Yield 52.6%; red solid (MeOH); mp: 153–154 °C; IR (KBr): νmax = 3384, 3064, 2971, 2927, 2907, 1581, 1513, 1438, 1373 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.30 (s, 1H, 9-OH), 12.36 (s, 1H, 10-OH), 8.51 (t, J = 6.4 Hz, 1H, NH), 7.36–7.25 (m, 5H, Ar-H), 5.58 (s, 1H, 7-H), 5.09 (d, J = 4.8 Hz, 1H, 1-OH), 4.90 (d, J = 4.6 Hz, 1H, 2-OH), 4.74 (t, J = 4.8 Hz, 1H, 1-H), 4.49 (d, J = 6.4 Hz, 2H, NHCH2Ph), 4.44 (s, 1H, 3-OH), 3.52 (t, J = 4.6 Hz, 1H, 2-H), 2.74 (d, J = 17.9 Hz, 1H, 4-Hb), 2.66 (d, J = 17.9 Hz, 1H, 4-Ha), 1.23 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 185.98 (C-8), 183.29 (C-5), 155.46 and 155.38 (C-9 and C-10), 149.54 (C-6), 139.57 (C-9a), 137.08 (C-1′), 133.24 (C-4a), 128.49 (C-3′ and C-5′), 127.16 and 127.12 (C-2′, C-4′ and C-6′), 109.67 (C-10a), 107.79 (C-8a), 99.84 (C-7), 76.41 (C-2), 69.38 (C-3), 68.56 (C-1), 45.25 (NHCH2), 34.79 (C-4), 25.70 (3-CH3); EIMS m/z 411 [M]+ (4), 391 (10), 359 (12), 337 (13), 302 (23), 284 (11), 218 (19), 204 (5), 91 (100).
6-(p-Methoxybenzylamino)-6-demethoxybostrycin (18). Yield 55.3%; red solid (MeOH); mp: 149–150 °C; IR (KBr): νmax = 3375, 3072, 2968, 2932, 2912, 2837, 1581, 1513, 1438, 1399 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.33 (s, 1H, 9-OH), 12.35 (s, 1H, 10-OH), 8.47 (t, J = 6.4 Hz, 1H, NH), 7.32–6.88 (m, 4H, Ar-H), 5.59 (s, 1H, 7-H), 5.10 (d, J = 4.8 Hz, 1H, 1-OH), 4.91 (d, J = 4.6 Hz, 1H, 2-OH), 4.74 (t, J = 4.8 Hz, 1H, 1-H), 4.45 (s, 1H, 3-OH), 4.41 (d, J = 6.4 Hz, 2H, NHCH2Ph), 3.73 (s, 3H, 4′-OMe), 3.51 (t, J = 4.6 Hz, 1H, 2-H), 2.73 (d, J = 17.8 Hz, 1H, 4-Hb), 2.65 (d, J = 17.8 Hz, 1H, 4-Ha), 1.22 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 185.94 (C-8), 183.37 (C-5), 158.44 (C-4′), 155.45 and 155.35 (C-9 and C-10), 149.40 (C-6), 139.59 (C-9a), 133.20 (C-4a), 128.89 and 128.55 (C-1′, C-2′ and C-6′), 113.91 (C-3′ and C-5′), 109.66 (C-10a), 107.80 (C-8a), 99.74 (C-7), 76.42 (C-2), 69.40 (C-3), 68.58 (C-1), 55.02 (4′-OMe), 44.74 (NHCH2), 34.80 (C-4), 25.72 (3-CH3); EIMS m/z 441 [M]+ (2), 425 (3), 407 (2), 389 (1), 320 (3), 302 (2), 274 (1), 232 (4), 121 (100).
6-(p-Fluorobenzylamino)-6-demethoxybostrycin (19). Yield 43.2%; red solid (MeOH); mp: 147–148 °C; IR (KBr): νmax = 3376, 3076, 2971, 2928, 2858, 1582, 1510, 1442, 1420 cm–1; 1H NMR (400 MHz, DMSO-d6): δ 14.29 (s, 1H, 9-OH), 12.35 (s, 1H, 10-OH), 8.49 (t, J = 6.4 Hz, 1H, NH), 7.45–7.14 (m, 4H, Ar-H), 5.60 (s, 1H, 7-H), 5.09 (d, J = 4.7 Hz, 1H, 1-OH), 4.90 (d, J = 4.8 Hz, 1H, 2-OH), 4.74 (t, J = 4.7 Hz, 1H, 1-H), 4.47 (d, J = 6.4 Hz, 2H, NHCH2Ph), 4.44 (s, 1H, 3-OH), 3.52 (t, J = 4.8 Hz, 1H, 2-H), 2.74 (d, J = 17.8 Hz, 1H, 4-Hb), 2.65 (d, J = 17.8 Hz, 1H, 4-Ha), 1.23 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 186.02 (C-8), 183.26 (C-5), 161.31 (C-4′), 155.46 and 155.36 (C-9 and C-10), 149.42 (C-6), 139.55 (C-9a), 133.26 (C-4a), 129.25 and 129.17 (C-1′, C-2′ and C-6′), 115.21 (C-3′ and C-5′), 109.66 (C-10a), 107.78 (C-8a), 99.84 (C-7), 76.41 (C-2), 69.38 (C-3), 68.56 (C-1), 44.48 (NHCH2), 34.78 (C-4), 25.69 (3-CH3); ESIMS m/z 428 [M − 1]−.
6-(Piperidin-1-yl)-6-demethoxybostrycin (20). Yield 55%; red solid (MeOH); mp: 199–200 °C; IR (KBr): νmax = 3557, 3399, 3054, 2928, 2855, 1597, 1576, 1548, 1447, 1429 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.10 (s, 1H, 9-OH), 12.58 (s, 1H, 10-OH), 6.03 (s, 1H, 7-H), 5.08 (d, J = 4.9 Hz, 1H, 1-OH), 4.88 (d, J = 4.7 Hz, 1H, 2-OH), 4.78 (t, J = 4.9 Hz, 1H, 1-H), 4.42 (s, 1H, 3-OH), 3.58 (br s, 4H, 2′-CH2 and 6′-CH2), 3.55 (t, J = 4.7 Hz, 1H, 2-H), 2.76 (d, J = 17.9 Hz, 1H, 4-Hb), 2.67 (d, J = 17.9 Hz, 1H, 4-Ha), 1.68 (br s, 6H, 3′-CH2, 4′-CH2 and 5′-CH2), 1.25 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 185.33 (C-8), 184.27 (C-5), 156.12 and 155.91 (C-9 and C-10), 153.93 (C-6), 138.50 (C-9a), 134.27 (C-4a), 111.14 (C-10a), 109.30 (C-7), 108.02 (C-8a), 76.45 (C-2), 69.45 (C-3), 68.50 (C-1), 50.40 (C-2′ and C-6′), 35.00 (C-4), 25.75 (3-CH3), 25.46 (C-3′ and C-5′), 23.67 (C-4′); EIMS m/z 389 [M]+ (37), 371 (30), 353 (17), 316 (100), 300 (12), 286 (24), 258 (10), 242 (9).
6-(4′-Methylpiperidin-1-yl)-6-demethoxybostrycin (21). Yield 56.7%; red solid (MeOH); mp: 162–163 °C; IR (KBr): νmax = 3559, 3408, 3055, 2948, 2927, 2855, 1597, 1580, 1550, 1451, 1432 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.10 (s, 1H, 9-OH), 12.59 (s, 1H, 10-OH), 6.04 (s, 1H, 7-H), 5.09 (d, J = 4.8 Hz, 1H, 1-OH), 4.88 (d, J = 4.6 Hz, 1H, 2-OH), 4.78 (t, J = 4.8 Hz, 1H, 1-H), 4.42 (s, 1H, 3-OH), 4.13 (m, 2H, 2′-Hb and 6′-Hb), 3.55 (t, J = 4.6 Hz, 1H, 2-H), 3.05 (m, 2H, 2′-Ha and 6′-Ha), 2.76 (d, J = 17.9 Hz, 1H, 4-Hb), 2.68 (d, J = 17.9 Hz, 1H, 4-Ha), 1.71 (m, 1H, 4′-H), 1.70 (m, 2H, 3′-Hb and 5′-Hb), 1.27 (m, 2H, 3′-Ha and 5′-Ha), 1.26 (s, 3H, 3-CH3), 0.97 (d, J = 6.1 Hz, 3H, 4′-CH3); 13C NMR (100 MHz, DMSO-d6): δ 185.13 (C-8), 184.04 (C-5), 156.33 and 156.05 (C-9 and C-10), 153.83 (C-6), 138.48 (C-9a), 134.32 (C-4a), 111.11 (C-10a), 109.46 (C-7), 107.99 (C-8a), 76.43 (C-2), 69.42 (C-3), 68.50 (C-1), 49.63 and 49.56 (C-2′ and C-6′), 34.99 (C-4), 33.61 and 33.52 (C-3′ and C-5′), 29.99 (C-4′), 25.71 (3-CH3), 21.41 (4′-CH3); EIMS m/z 403 [M]+ (33), 385 (34), 367 (50), 330 (100), 314 (31), 300 (28), 286 (20), 270 (15).
6-(4′-Phenylpiperidin-1-yl)-6-demethoxybostrycin (22). Yield 45.6%; red solid (MeOH); mp: 221–222 °C; IR (KBr): νmax = 3538, 3397, 3033, 2956, 2933, 2900, 2870, 1570, 1539, 1495, 1455 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 14.07 (s, 1H, 9-OH), 12.60 (s, 1H, 10-OH), 7.35–7.26 (m, 4H, Ar-H), 7.21 (m, 1H, Ar-H), 6.10 (s, 1H, 7-H), 5.12 (d, J = 4.7 Hz, 1H, 1-OH), 4.90 (d, J = 4.8 Hz, 1H, 2-OH), 4.77 (t, J = 4.7 Hz, 1H, 1-H), 4.44 (s, 1H, 3-OH), 4.27 (m, 2H, 2′-Hb and 6′-Hb), 3.53 (t, J = 4.8 Hz, 1H, 2-H), 3.15 (m, 2H, 2′-Ha and 6′-Ha), 2.83 (m, 1H, 4′-H), 2.75 (d, J = 17.9 Hz, 1H, 4-Hb), 2.66 (d, J = 17.9 Hz, 1H, 4-Ha), 1.91–1.76 (m, 4H, 3′-CH2 and 5′-CH2), 1.24 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 185.24 (C-8), 184.04 (C-5), 156.35 and 156.12 (C-9 and C-10), 153.80 (C-6), 145.33 (C-1″), 138.53 (C-9a), 134.39 (C-4a), 128.38, 126.67 and 126.19 (C-2″, C-3″, C-4″, C-5″ and C-6″), 111.12 (C-10a), 109.84 (C-7), 108.01 (C-8a), 76.43 (C-2), 69.42 (C-3), 68.49 (C-1), 50.00 and 49.92 (C-2′ and C-6′), 41.32 (C-4′), 34.99 (C-4), 32.77 and 32.66 (C-3′ and C-5′), 25.71 (3-CH3); EIMS m/z 465 [M]+ (53), 445 (85), 429 (91), 413 (66), 392 (100), 376 (12), 362 (16), 328 (62).
3.3.6. General Procedure: Synthesis of Compounds 23–29
To a solution of 1 (1 equiv, 50 mg, 0.149 mmol) and triethylamine (8 equiv) in 10 mL of methanol was added the corresponding thiol (4 equiv). The reaction mixture was stirred at 0–5 °C until the starting material disappeared. The solvent was removed under reduced pressure. The resulting residue was purified on a silica gel column using dichloromethane–methanol as eluent, and then a C18 reversed phase silica gel column using methanol–water as eluent to obtain the corresponding products.
6,7-bis(Ethylthio)-6-demethoxybostrycin (23). Yield 60.4%; red solid (MeOH); mp: 180–181 °C; IR (KBr): νmax = 3561, 3379, 2968, 2923, 2865, 1604, 1572, 1486, 1447, 1426 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 13.22 (s, 1H, 9-OH), 13.04 (s, 1H, 10-OH), 5.29 (d, J = 4.5 Hz, 1H, 1-OH), 4.94 (d, J = 4.4 Hz, 1H, 2-OH), 4.75 (br t, 1H, 1-H), 4.49 (s, 1H, 3-OH), 3.53 (t, J = 4.4 Hz, 1H, 2-H), 3.30–3.24 (m, 4H, 1′-CH2 and 1″-CH2), 2.74 (d, J = 18.5 Hz, 1H, 4-Hb), 2.67 (d, J = 18.5 Hz, 1H, 4-Ha), 1.24–1.20 (m, 9H, 3-CH3, 2′-CH3 and 2″-CH3); 13C NMR(100 MHz, DMSO-d6): δ 175.67 (C-5), 175.55 (C-8), 164.61 (C-9), 163.16 (C-10), 145.75 (C-7), 145.07 (C-6), 138.58 and 138.54 (C-4a and C-9a), 109.69 (C-10a), 109.32 (C-8a), 76.36 (C-2), 69.24 (C-3), 68.17 (C-1), 34.95 (C-4), 28.70 and 28.64 (C-1′ and C-1″), 25.53 (3-CH3), 15.03 and 15.00 (C-2′ and C-2″); EIMS m/z 426 [M]+ (8), 408 (10), 390 (3), 379 (21), 361 (100), 345 (28), 333 (79), 319 (22).
6,7-bis(n-Butylthio)-6-demethoxybostrycin (24). Yield 51.2%; red solid (MeOH); mp: 124–125 °C; IR (KBr): νmax = 3551, 3400, 2958, 2929, 2871, 1599, 1532, 1431, 1377 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 13.23 (s, 1H, 9-OH), 13.05 (s, 1H, 10-OH), 5.29 (br s, 1H, 1-OH), 4.94 (br s, 1H, 2-OH), 4.75 (br s, 1H, 1-H), 4.49 (s, 1H, 3-OH), 3.53 (d, J = 4.4 Hz, 1H, 2-H), 3.29–3.20 (m, 4H, 1′-CH2 and 1″-CH2), 2.73 (d, J = 18.4 Hz, 1H, 4-Hb), 2.67 (d, J = 18.4 Hz, 1H, 4-Ha), 1.58–1.46 (m, 4H, 2′-CH2 and 2″-CH2), 1.39 (sextet, J = 7.2 Hz, 4H, 3′-CH2 and 3″-CH2), 1.23 (s, 3H, 3-CH3), 0.86 (br t, J = 7.2 Hz, 6H, 4′-CH3 and 4″-CH3); 13C NMR (100 MHz, DMSO-d6): δ 175.85 (C-5), 175.74 (C-8), 164.55 (C-9), 163.07 (C-10), 146.16 (C-7), 145.52 (C-6), 138.59 and 138.55 (C-4a and C-9a), 109.76 (C-10a), 109.37 (C-8a), 76.39 (C-2), 69.30 (C-3), 68.20 (C-1), 35.00 (C-4), 34.15 and 34.09 (C-1′ and C-1″), 31.84 and 31.81 (C-2′ and C-2″), 25.61 (3-CH3), 21.10 (C-3′ and C-3″), 13.37 (C-4′ and C-4″); EIMS m/z 482 [M]+ (2), 464 (3), 446 (8), 430 (2), 405 (28), 389 (100), 373 (31), 361 (14).
6,7-bis(n-Hexylthio)-6-demethoxybostrycin (25). Yield 42.6%; red solid (MeOH); mp: 112–113°C; IR (KBr): νmax = 3545, 3370, 2956, 2925, 2854, 1598, 1433, 1419, 1379 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 13.23 (s, 1H, 9-OH), 13.05 (s, 1H, 10-OH), 5.29 (d, J = 4.9 Hz, 1H, 1-OH), 4.94 (br s, 1H, 2-OH), 4.75 (br t, 1H, 1-H), 4.49 (s, 1H, 3-OH), 3.53 (br d, 1H, 2-H), 3.29–3.19 (m, 4H, 1′-CH2 and 1″-CH2), 2.73 (d, J = 18.4 Hz, 1H, 4-Hb), 2.67 (d, J = 18.4 Hz, 1H, 4-Ha), 1.59–1.47 (m, 4H, 2′-CH2 and 2″-CH2), 1.44–1.30 (m, 4H, 3′-CH2 and 3″-CH2), 1.23 (br s, 11H, 3-CH3, 4′-CH2, 4″-CH2, 5′-CH2 and 5″-CH2), 0.87–0.79 (m, 6H, 6′-CH3 and 6″-CH3); 13C NMR (100 MHz, DMSO-d6): δ 175.87 (C-5), 175.75 (C-8), 164.52 (C-9), 163.03 (C-10), 146.17 (C-7), 145.53 (C-6), 138.58 and 138.54 (C-4a and C-9a), 109.74 (C-10a), 109.36 (C-8a), 76.38 (C-2), 69.30 (C-3), 68.20 (C-1), 34.99 (C-4), 34.48 and 34.41 (C-1′ and C-1″), 30.65, 29.71, 29.68 and 27.58 (C-2′, C-2″, C-3′, C-3″, C-4′ and C-4″), 25.60 (3-CH3), 21.91 (C-5′ and C-5″), 13.76 (C-6′ and C-6″); EIMS m/z 538 [M]+ (4), 502 (4), 433 (26), 417 (100), 401 (21), 389 (12), 347 (7), 335 (20).
6,7-bis(2′-Hydroxyethylthio)-6-demethoxybostrycin (26). Yield 28.7%; red solid (MeOH); mp: 156–158 °C; IR (KBr): νmax = 3560, 3405, 2960, 2928, 2874, 2862, 1606, 1573, 1488, 1426 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 13.17 (s, 1H, 9-OH), 12.99 (s, 1H, 10-OH), 5.27 (d, J = 4.3 Hz, 1H, 1-OH), 4.92 (br d, 1H, 2-OH), 4.89 and 4.88 (each br t, 1H, 2′-OH and 2″-OH), 4.77 (br t, 1H, 1-H), 4.47 (s, 1H, 3-OH), 3.61 (q, J = 4.8 Hz, 4H, 2′-CH2 and 2″-CH2), 3.55 (br t, 1H, 2-H), 3.41–3.32 (m, 4H, 1′-CH2 and 1″-CH2), 2.76 (d, J = 18.4 Hz, 1H, 4-Hb), 2.69 (d, J = 18.4 Hz, 1H, 4-Ha), 1.25 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 177.50 (C-5), 177.37 (C-8), 162.54 (C-9), 160.90 (C-10), 146.93 (C-7), 146.41 (C-6), 138.10 and 138.02 (C-4a and C-9a), 109.91 (C-10a), 109.49 (C-8a), 76.45 (C-2), 69.36 (C-3), 68.26 (C-1), 61.05 (C-2′ and C-2″), 37.13 and 37.09 (C-1′ and C-1″), 35.06 (C-4), 25.68 (3-CH3); ESIMS m/z 457 [M − 1]−.
6,7-bis(3′-Hydroxy-n-propylthio)-6-demethoxybostrycin (27). Yield 32.5%; red solid (MeOH); mp: 150–151 °C; IR (KBr): νmax = 3550, 3423, 2993, 2925, 2874, 2855, 1599, 1528, 1430, 1403, 1375 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 13.20 (s, 1H, 9-OH), 13.03 (s, 1H, 10-OH), 5.25 (d, J = 4.3 Hz, 1H, 1-OH), 4.90 (d, J = 4.2 Hz, 1H, 2-OH), 4.75 (br t, 1H, 1-H), 4.50–4.43 (m, 3H, 3′-OH, 3″-OH and 3-OH), 3.52 (t, J = 4.2 Hz, 1H, 2-H), 3.47 (q, J = 6.4 Hz, 4H, 3′-CH2 and 3″-CH2), 3.36–3.28 (m, 4H, 1′-CH2 and 1″-CH2), 2.74 (d, J = 18.4 Hz, 1H, 4-Hb), 2.67 (d, J = 18.4 Hz, 1H, 4-Ha), 1.68 (pentet, J = 6.4 Hz, 4H, 2′-CH2 and 2″-CH2), 1.23 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 176.23 (C-5), 176.12 (C-8), 164.14 (C-9), 162.61 (C-10), 146.32 (C-7), 145.73 (C-6), 138.51 and 138.48 (C-4a and C-9a), 109.85 (C-10a), 109.45 (C-8a), 76.43 (C-2), 69.35 (C-3), 68.23 (C-1), 59.09 (C-3′ and C-3″), 35.04 (C-4), 33.07 and 33.04 (C-1′ and C-1″), 31.46 and 31.40 (C-2′ and C-2″), 25.67 (3-CH3); ESIMS m/z 485 [M − 1]−.
6,7-(Ethan-1′,2′-yl-dithio)-6-demethoxybostrycin (28). Yield 24.8%; red solid (MeOH); mp: >300 °C; IR (KBr): νmax = 3417, 2966, 2925, 2857, 1588, 1513, 1436, 1375 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 12.84 (s, 1H, 9-OH), 12.67 (s, 1H, 10-OH), 5.26 (br s, 1H, 1-OH), 4.94 (d, J = 4.4 Hz, 1H, 2-OH), 4.75 (d, J = 4.6 Hz, 1H, 1-H), 4.49 (s, 1H, 3-OH), 3.53 (t, J = 4.4 Hz, 1H, 2-H), 3.35 (br s, 4H, 1′-CH2 and 2′-CH2), 2.75 (d, J = 18.2 Hz, 1H, 4-Hb), 2.68 (d, J = 18.2 Hz, 1H, 4-Ha), 1.23 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 180.54 and 180.42 (C-5 and C-8), 157.65 (C-9), 155.72 (C-10), 140.74 (C-7), 140.20 (C-6), 137.39 and 137.23 (C-4a and C-9a), 108.17 (C-10a), 107.66 (C-8a), 76.43 (C-2), 69.29 (C-3), 68.30 (C-1), 35.11 (C-4), 26.17 and 26.08 (C-1′ and C-2′), 25.67 (3-CH3); EIMS m/z 396 [M]+ (6), 376 (28), 360 (100), 344 (47), 332 (22), 307 (23), 294 (13), 279 (12).
6,7-(Butan-2′,3′-yl-dithio)-6-demethoxybostrycin (29). Yield 63.5%; red solid (MeOH); mp: 146–147 °C; IR (KBr): νmax = 3446, 3250, 2960, 2916, 2859, 1589, 1516, 1441, 1418 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 12.85 (s, 1H, 9-OH), 12.69 (s, 1H, 10-OH), 5.22 (br s, 1H, 1-OH), 4.91 (d, J = 4.6 Hz, 1H, 2-OH), 4.75 (d, J = 4.5 Hz, 1H, 1-H), 4.45 (s, 1H, 3-OH), 3.67 and 3.48 (each m, 1H, 2′-CH and 3′-CH), 3.54 (t, J = 4.6 Hz, 1H, 2-H), 2.75 (d, J = 18.3 Hz, 1H, 4-Hb), 2.68 (d, J = 18.3 Hz, 1H, 4-Ha), 1.32 and 1.30 (each d, J = 6.2 Hz, 3H, 1′-CH3 and 4′-CH3), 1.23 (s, 3H, 3-CH3); 13C NMR (100 MHz, DMSO-d6): δ 180.69 and 180.66 (C-5 and C-8), 157.58 (C-9), 155.64 (C-10), 139.83 (C-7), 138.71 (C-6), 137.39 and 137.18 (C-4a and C-9a), 108.38 (C-10a), 107.86 (C-8a), 76.46 (C-2), 69.33 (C-3), 68.32 (C-1), 35.11 (C-4), 25.70 (3-CH3), 22.99 and 22.89 (C-2′ and C-3′), 17.60 (C-1′ and C-4′); EIMS m/z 424 [M]+ (8), 406 (5), 388 (3), 351 (29), 335 (5), 322 (9), 307 (5), 295 (13), 71 (100).