Claims
- 1. The substantially pure compound Ecteinascidin 729, free of cellular components of the marine tunicate Ecteinascidia turbinata, said compound having the following physicochemical characteristics: TLC (SiO.sub.2) R.sub.4 -0.28 (3:1 ethyl acetate-methanol), 0.26 (9:1 chloroform-methanol); HPLC retention time, 15.7 min. [Whatman Partisil 10 ODS-3, 10.times.250 mm, 70:30 methanol-aqueous Tris (0.05M, pH 7.5), 2.8 mL/min.]; UV max (CH.sub.3 OH), 202 nm (.epsilon. 61 000), 244 (sh) (11 000), 283 (5 000), 289 (4 700), (0.1N HCl) 204 (61 000), 244 (sh) (9 600), 283 (4 800), 289 (4 500), (0.1N KOH) 215 (33 800), 258 (8 200), 290 (6 400); IR (CCl.sub.4), 3555, 3535, 2953, 2927, 2855, 1770, 1742, 1504, 1466, 1462, 1454, 1432, 1369, 1239, 1196, 1168, 1122, 1100, 1086, 1054, 1032, 997, 960 cm.sup.-1 ; .sup.1 H NMR (360 MHz, CDCl.sub.3) .epsilon. 6.63 (s, 1H), 6.48 (s, 1H), 6.44 (s, 1H), 6.04 (d, J-0.7 Hz, 1H), 5.95 (d, J-0.9 Hz, 1H), 5.15 (d, J-10.7 Hz, 1H), 4.84 (bs, 1H), 4.52 (d, J-3.5 Hz, 1H), 4.48 (bs, 1H), 4.38 (d, J-4.9 Hz, 1H), 4.04 (d, J-11 Hz, 1H), 3.78 (s, 3H), 3.62 (s, 3H), 3.61 (m, 2H), 3.10 (m, 1H), 3.02 (d, J-18 Hz, 1H), 2.90 (dd, J-9, 18 Hz, 1H), 2.80 (m, 1H), 2.60 (m, 1H), 2.50 (m, 1H), 2.35 (m, 1H), 2.31 (s, 3H), 2.27 (s, 3H), 2.20 (m, 1H), 2.03 (s, 3H); FABMS m/z (rel. intensity) 730.2493 (30), 495 (2), 493 (2), 481 (2), 479 (2), 463 (4), 461 (2), 449 (4), 205 (8), 204 (8), 190 (8); B/E linked scan on m/z 729, m/z 711, 696, 683, 509, 495, 481, 479, 461, 449; optical rotation [.alpha.].sub.D.sup.25 +112.degree. (c 0.01, CH.sub.3 OH).
- 2. The substantially pure compound Ecteinascidin 743, free of cellular components of the marine tunicate Ecteinascidia turbinata, said compound having the following physicochemical characteristics: TLC (SiO.sub.2) R.sub.f -0.58 (3:1 ethyl acetate-methanol), 0.44 (9:1 chloroform-methanol); HPLC retention time, 18.8 min. [Whatman Partisil 10 ODS-3, 10.times.250 mm, 70:30 methanol-aqueous Tris (0.05M, pH 7.5), 2.8 mL/min.]; UV max (CH.sub.3 OH) 202 nm (.epsilon. 81 000), 240 (sh) (15 000), 284 (6 600), 289 (6 400), (0.1N HCl) 205 (76 000), 240 (sh), (12 000), 285 (7 500), 289 (7 200), (0.1N KOH) 216 (50 000), 256 (12 700) 290 (9 000); IR (CCl.sub.4) 3549, 3530, 2992 (weak), 2929, 2848, 2803 (weak), 1764, 1739, 1597 (weak), 1511, 1501, 1460, 1445, 1425, 1365, 1350, 1195, 1160, 1115, 1102, 1098, 1082, 1058, 1048, 1024, 990, 950, 915, 907, cm.sup.-1 ; .sup.1 H NMR (500 MHz, CDCl.sub.3) .delta. 6.62 (s, 1H), 6.48 (s, 1H), 6.46 (s, 1H), 6.03 (d, J-1.2 Hz, 1H), 5.95 (d, J-1.3 Hz, 1H), 5.7 (bs, exchanges, 1H), 5.14 (dd, J-0.9, 11.3 Hz, 1H), 4.83 (bs, 1H), 4.50 (d, J-3.3 Hz, 1H), 4.50 (bs, 1H), 4.18 (d, J-4.2 Hz, 1H), 4.06 (dd, J-2.5, 11.3 Hz, 1H), 3.81 (s, 3H), 3.63 (s, 3H), 3.59 (bd, J-4.4 Hz, 1H), 3.23 (m, 1H), 3.14 (ddd, J-11, 10, 4 Hz, 1H), 2.91 (bd, J-18 Hz, 1H), 2.88 (dd, J-9, 18 Hz, 1H), 2.82 (m, 1H), 2.62 (ddd, J-16, 10, 4 Hz, 1H), 2.49 (ddd, J-16, 4, 4 Hz, 1H), 2.37 (bd, J-13.9 Hz, 1), 2.33 (s, 3H), 2.28 (s, 3H), 2.19 (s, 3H), 2.18 (d, J-13.9 Hz, 1H), 2.04 (s, 3H); .sup.13 C NMR (75.4 MHz and 125.7 MHz, CDCl.sub.3) .delta. 9.6 (q), 15.7 (1),20.4 (q), 24.1 (t), 28.7 (t), 39.6 (t), 41.3 (q), 42.1 (t), 42.1 (d), 54.8 (d), 55.0 (q), 55. 9 (d), 57.7 (d), 57.8 (d), 60.2 (q), 61.3 (t), 64.6 (s), 82.0 (d), 101.6 (t), 109.8 (d), 112.5 (s), 114.1 (d), 115.9 (s), 118.1 (s), 120.9 (d), 121.9 (s), 126.0 (s), 129.2 (s), 129.2 s), 131.5 (s), 140.5 (s), 141.3 (s), 143.0 (s), 144.3 (s), 144.5 (s), 145.1 (s), 147.5 (s), 168.3 (s), 172.5 (s); FABMS m/z (rel. intensity) 744.2648 (100), 699.2766 (4), 495.2064 (15), 477.1979 (15), 475 (9), 463.1837 (25), 281 (39), 204.1027 (71); LC/FABMS m/z (rel. intensity) 744 (34), 495 (12), 493 (16), 477 (14), 475 (10), 463 (14), 234 (42), 218 (64), 204 (100), 189 (62), 174 (28), 160 (22); EIMS m/z 217.0737305, 191.0941620, 176.0696716; ESCA (mole percent) C (73.1), O (20.4), N (5.2), S (1.3); optical rotation [.alpha.].sub.D.sup.25 +114.degree. (c 0.1, CH.sub.3 OH); or a derivative thereof selected from the group consisting of:
- deacetyl-, dioxy-, diacetyl-, monoacetyl-, mono-O-methyl-, di-O-methyl-, monooxy-, tetracetyl-, or p-bromobenzoyl.
- 3. The substantially pure compound Ecteinascidin 745, free of cellular components of the marine tunicate Ecteinascidia turbinata, said compound having the following physicochemical characteristics: TLC (SiO.sub.2) R.sub.4 -0.42 (3:1 ethyl acetate-methanol, 0.38 (9:1 chloroform-methanol); HPLC retention time, 29.8 min. [Whatman Partisil 10 ODS-3, 10.times.250 mm, 70:30 methanol-aqueous Tris (0.05M, pH 7.5), 2.8 mL/min.]; UV max (CH.sub.3 OH) 202 (.epsilon. 52 000), 240 (sh) (11 000), 281 (5 600), 287 (5 400), (0.1N HCL), 204 (51 000), 240 (sh) (9 500), 281 (5 200), 287 (5 200), (0.1N KOH), 215 (36 000), 254 (8 500), 290 (5 900), 298 (5 800); IR (CCl.sub.4) 3554, 3535, 2955, 2927, 2871, 2855, 1770, 1744, 1518, 1507, 1270, 1238, 1195, 1163, 1088, 1056 cm.sup.-1 ; .sup.1 H NMR (360 MHz, CDCl.sub.3), .delta. 6.62 (s, 1H), 6.52 (s, 1H), 6.47 (s, 1H), 6.02 (d, J-1.2 Hz, 1H), 5.97 (d, J-1.2 Hz, 1H), 5.74 (bs, exchanges, 1H), 5.14 (d, J-11.2 Hz, 1H), 4.5 (bs, 1H), 4.22 (bs, 1H), 4.11 (dd, J-2, 11 Hz, 1H), 3.79 (s, 3H), 3.68 (s, 1H), 3.63 (s, 3H), 3.31 (m, 1H), 3.23 (bs, 1H), 3.11 (m, 2H), 2.93 (m, 2H), 2.69 (m, 2H), 2.54 (m, 2H), 2.44 (d, J-14 Hz, 1H), 2.33 (s, 3H), 2.28 (s, 3H), 2.18 (s, 3H), 2.13 (m, 1H), 2.04 (s, 3H), ; FABMS m/z (rel. intensity) 746.2775 (100), 699 (8), 631 (8), 629 (8), 495 (19), 479 (42), 477 (52), 463 (36), 205 (64), 204 (64); LC/FABMS m/z (rel. intensity) 746 (44), 495 (18), 477 (20), 463 (32), 218 (42), 204 (100), 189 (62), 176 (32), 160 (20); optical rotation [.alpha.].sub.D.sup.25 +50.degree. (c 0.1, CH.sub.3 OH).
- 4. The substantially pure compound Ecteinascidin 759A, free of cellular components of the marine tunicate Ecteinascidia turbinata, said compound having the following physicochemical characteristics: TLC (SiO.sub.2) R.sub.f 0.6 (3:1 ethyl acetate-methanol), 0.3 (9:1 chloroform-methanol); HPLC retention time, 11.0 min. [Whatman Partisil 10 ODS-3, 10.times.250 mm, 70:30 methanol-aqueous Tris (0.05M, pH 7.5), 2.8 mL/min.]; UV max (CH.sub.3 OH) 203 nm (.epsilon. 43 000), 250 (sh) (6 500), 281 (3 000), 288 (2 600), (0.1N HCl) 205 (44 000), 250 (sh) (7 600), 281 (4 500), 288 (4 400), (0.1N KOH) 216 (39 000), 249 (3 900), 294 (4 600); IR (CCl.sub.4) 3696, 3555, 3532, 2926, 2854, 1770, 1744, 1670, 1466, 1252, 1240, 1194, 1091 cm.sup. -1 ; FABMS m/z (rel. intensity) 760.2563 (58), 581 (24), 493 (16), 463 (80), 461 (100); LC/FABMS m/z (rel. intensity) 760 (26), 509 (12), 493 (12), 463 (24), 449 (16), 246 (26), 232 (32), 224 (62), 218 (5), 204 (100), 189 (56), 174 (18), 160 (16); optical retention [.alpha.].sub.D.sup.25 +130.degree. (c 0.05, CH.sub.3 OH).
- 5. The substantially pure compound Ecteinascidin 759B, free of cellular components of the marine tunicate Ecteinascidia turbinata, said compound having the following physicochemical characteristics: TLC (SiO.sub.2) R.sub.f -0.6 (3:1 ethyl acetate-methanol), 0.3 (9:1 chloroform-methanol); HPLC retention time, 13.9 min. [Whatman Partisil 10 ODS-3, 10.times.250 mm, 70:30 methanol-aqueous Tris (0.05M, pH 7.5), 2.8 mL/min.]; UV max (CH.sub.3 OH) 208 nm (.epsilon. 60 000), 288 (4 800), 293 (4 500), (0.1N HCl) 209 (64 000), 288 (7 100), 293 (7 100), (0.1N KOH) 220 (45 000), 260 (10 000), 298 (7 600); IR (CCl.sub.4), 3555, 2933, 1770, 1743, 1590, 1514, 1465, 1453, 1446, 1431, 1368, 1356, 1330, 1288, 1264, 1240, 1193, 1163, 1124, 1110, 1089, 1032, 1006, 821 cm.sup.-1 ; FABMS m/z (rel. intensity) 760.2519 (100), 744 (71), 730 (19), 493 (29), 477 (43), 463 (76); LC/FABMS m/z (rel. intensity) 760 (38), 508 (8), 493 (18), 463 (26), 475 (14), 248 (30), 234 (48), 218 (86), 204 (100), 189 (56), 176 (26), 160 (32); optical rotation [.alpha.].sub.D.sup.25 +167.degree. (c 0.1, CH.sub.3 OH).
- 6. The substantially pure compound Ecteinascidin 770, free of cellular components of the marine tunicate Ecteinascidia turbinata, said compound having the following physicochemical characteristics: TLC (SiO.sub.2) R.sub.f -0.6 (3:1 ethyl acetate-methanol), 0.3 (9:1 chloroform-methanol); HPLC retention time, 12.0 min. [Whatman Partisil 10 ODS-3, 10.times.250 mm, 70:30 methanol-aqueous Tris (0.05M, pH 7.5), 2.8 mL/min.]; UV max (CH.sub.3 OH) 342 nm (.epsilon. 3 200), 329 (3 900), 299 (22 000), 263 (25 000), 240 (58 000), 234 (55 000), 216 (66 000), (0.1N HCl) 342 (4 900), 329 (5 700), 299 (24 000), 263 (29 000), 240 (58 000), 234 (57 000), 216 (71 000), (0.1N KOH) 342 (3 700), 329 (4 900), 299 (22 000), 263 (28 000), 240 (58 000), 234 (57 000), 227 (57 000); IR (CCl.sub.4) 3555, 3535, 3484, 2929, 2910, 1770, 1742, 1607, 1516, 1509, 1504, 1494, 1462, 1450, 1433, 1325, 1237, 1193 cm.sup.-1 ; .sup.1 H NMR (300 MHz, CDCl.sub.3), .epsilon. 6.60 (s, 1H), 6.47 (s, 1H), 6.45 (s, 1H), 6.05 (s, 1H), 5.98 (s, 1H), 5.02 (d, J-11.4 Hz, 1H), 4.57 (bs, 1H), 4.32 (bs, 1H), 4.28 (d, J-5.3 Hz, 1H), 4.18 (d, J-2.5 Hz, 1H), 4.12 (dd, J-2.1, 11.5 Hz, 1H), 3.78 (s, 3H), 3.62 (s, 3H), 3.50 (d, J-5 Hz, 1H), 3.42 (m, 1H), 3.10 (ddd, J-4, 10, 11 Hz, 1H), 2.94 (m, 2H), 2.79 (m, 1H), 2.61 (m, 1H), 2.47 (m, 1H), 2.34 (m, 1H), 2.32 (s, 3H), 2.27 (s, 3H), 2.20 (s, 3H), 2.09 (m, 1H), 2.04 (s, 3H); FABMS m/z (rel. intensity) 771.2700 (48), 760 (8), 744 (20), 723 (12), 488 (12), 463 (14), 461 (20), 205 (50), 204 (80); optical rotation [.alpha.].sub.D.sup.25 +52.degree. (c 0.1, CH.sub.3 OH).
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of U.S. Ser. No. 07/278,629, filed 1 Dec. 1988, now abandoned, which is a continuation of PCT/US87/01226 filed 1 June 1987, which is a continuation-in-part of U.S.. Ser. No. 006,395, filed 23 Jan. 1987, now abandoned, which is a continuation-in-part of U.S. Ser. No. 898,906, filed 21 Aug. 1986, now abandoned, which is a continuation-in-part of U.S. Ser. No. 872,189, filed 9 June 1986, now abandoned.
Non-Patent Literature Citations (1)
Entry |
Lichter et al., in Food and Drugs from the Sea Proceedings (1972), Marine Technology Society, Washington, D.C. 1973, pp. 117-127. |
Continuations (1)
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Date |
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1226 |
Jun 1987 |
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Continuation in Parts (4)
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278629 |
Dec 1988 |
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6395 |
Jan 1987 |
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898906 |
Aug 1986 |
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872189 |
Jun 1986 |
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