TREA

Epothilone side components

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Information

  • Patent Application
  • 20040049051
  • Publication Number
    20040049051
  • Date Filed
    June 06, 2003
    21 years ago
  • Date Published
    March 11, 2004
    20 years ago
Information
Abstract
The invention concerns compounds which can be obtained by fermenting DSM 6773, especially epothilones A1, A2, A8, A9, B10, C1, C2, C3, C4, C5, C6, C7, C8, C9, D1, D2, D5, G1, G2, H1, H2, I1, I2, I3, I4, I5, I6 and K and trans-epothilones C1 and C2.
Description


[0002] The invention concerns compounds which in the present context are designated epothilone side components, viz. compounds 5 to 13 and 16 to 39. These compounds can be produced by fermenting DSM 6773 in accordance to DE 41 38 042.8.





[0003] Characterizing data of the compounds according to the invention will be compiled as follows.

[0004] Production: The processing of a raw epothilone mixture, which has been produced by fermenting DSM 6773 in a 900 1 fermentor, can be drawn schematically from FIGS. 1 to 2.

[0005] Activities: cf. table 1
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[0006] Epothilone A1 (5): colorless amorphous solid; [α]22D-69 (c 0.1, MeOH); UV (MeOH) λmax nm (ε) 208 (19600), 247 (13600); IR (KBr) νmax 3437, 2959, 2931, 2876, 1732, 1710, 1455, 1259, 978 cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.95 (1H, s, H-19), 6.60 (1H, bs, H-17), 5.68 (1H, dd, J=4.4, 4.0 Hz, H-15), 4.12 (1H, m, H-33), 3.71 (1H, m, H-7), 3.52 (1H, bs, 7-OH), 3.37 (1H, bd, J=7.5 Hz, 3-OH), 3.21 (1H, dq, J=7.7, 7.0 Hz, H-4), 3.02 (1H, ddd, J=9.2, 4.5, 2.8 Hz, H-13), 2.87 (1H, ddd, J=8.3, 4.5, 3.7 Hz, H-12), 2.78 (1H, dd, J=16.8, 4.3 Hz, H-2a), 2.70 (3H, s, H-21), 2.66 (1H, dq, J=3.9, 7.0 Hz, H-6), 2.65 (1H, dd, J=16.8, 5.2 Hz, H-2b), 2.16 (1H, ddd, J=15.4, 4.4, 2.8 Hz, H-14 a), 2.12 (3H, bs, H-27), 1.91 (1H, ddd, J=15.4, 9.2, 4.0 Hz, H-14b), 1.63 (1H, m, H-10a), 1.62 (2H, m, H-11), 1.59 (1H, m, H-9a), 1.52 (1H, m, H-10b), 1.39 (1H, m, H-8), 1.35 (1H, m, H-9b), 1.211 (3H, d; J=7.0 Hz, H-2-3), 1.207 (3H, d, J=7.0 Hz, H-24), 0.89 (3H, d, J=6.9 Hz, H-25); EIMS m/z 479 [M]+ (21), 3322 (31), 306 (65), 304 (47), 168 (45), 166 (73), 164 (100), 151 (30), 140 (35); HREIMS m/z 479.2317 (calcd. for C27H41NO5S, 479.2342).

[0007] Epothilone A2 (6): colorless amorphous solid; [α]22D+12.0 (c 1.0, MeOH); UV (MeOH) λmax nm (ε) 210 (15100), 248 (15500); IR (KBr) νmax 3438, 2963, 2929, 2875, 1734, 1706, 1458, 1262, 981 cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.98 (1H, s, H-19), 6.63 (1H, bs, H-17), 5.40 (1H, dd, J=8.3, 3.4 Hz, H-15), 4.26 (1H, ddd, J=8.5, 4.8, 4.7 Hz, H-3), 3.85 (1H, dd, J=7.9, 2.6 Hz, H-7), 3.54 (1H, bs, 3-OH), 3.09 (1H, dq, J=4.8, 7.0 Hz, H-4), 3.01 (1H, ddd, J-8.3, 4.8, 4.6 Hz, H-13), 2.98 (1H, dq, J=7.9, 7.0 Hz, H-6), 2.89 (1H, ddd, J=6.7, 4.6, 4.4 Hz, H12), 2.68 (3H, s, H-21), 2.60 (1H, dd, J=15.1, 8.5 Hz, H-2a), 2.52 (1H, bs, 7-OH), 2.50 (1H, dd, J=15.1, 4.7 Hz, H-2b), 2.18 (1H, ddd, J=15.0, 4.8,3.4 Hz, H-14a), 2.11 (3H, d, J=1.3 Hz, H-27), 1.82 (1H, ddd, J=15.0, 8.3, 8.1 Hz, H-14b), 1.63 (1H, m, H-8), 1.61 (2H, m, H-11a and H-10a), 1.46 (1H, m, H-1 lb), 1.39 (2H, m, H-9), 1.31 (1H, m, H-10b), 1.22 (3H, d, J=7.0 Hz, H-24), 1.15 (3H, d, J=7.0 Hz, H-22), 1.01 (3H, d, J=6.9 Hz, H-25); 13C NMR (CDCl3, 100 MHz) δ 216.2 (s, C-5), 170.1 (s, C-1), 164.9 (s, C-20), 152.0 (s, C-18), 137.0 (s, C-16), 120.3 (d, C-17), 116.5 (d, C-19), 76.7 (d, C-15), 75.6 (d, C-7), 69.1 (d, C-3), 57.1 (d, C-12), 54.3 (d, C-13), 50.3 (d, C-4), 49.6 (d, C-6), 39.4 (t, C-2), 35.5 (d, C-8), 32.2 (t, C-14), 29.6 (t, C-9), 27.6 (t, C-11), 23.9 (t, C-10), 19.2 (q, C-21), 18.0 (q, C-25), 15.6 (q, C-27), 13.9 (q, C-24), 12.4 (q, C-22); EIMS m/z 479 [M]+ (18), 322 (38), 306 (78), 304 (59), 168 (48), 166 (96), 164 (100), 151 (33), 140 (38); HREIMS m/z 479.2318 (calcd. for C27H41NO5S, 479.2342).

[0008] Epothilone A8 (7): colorless amorphous solid; [α]22D-76.2 (c 1.0, MeOH); UV (MeOH) λmax nm (6) 210 (15300), 248 (15500); IR (KBr) νmax 3440, 2967, 2932, 2876, 1736, 1691, 1467, 1252, 979 cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.95 (1H, s, H-19), 6.64 (1H, dd, J=15.6, 0.9 Hz, H-17), 6.52 (1H, dd, J=15.6, 6.6 Hz, H-16), 5.68 (1H, dddd, J=7.8, 6.6, 3.2, 0.9 Hz, H 15), 4.11 (1H, ddd, J=10.1, 6.6, 3.5 Hz, H-3), 3.78 (1H, ddd, J=5.2, 3.2, 3.2 Hz, H-7), 3.66 (1H, d,.1=6.6 Hz, 3-01-1), 3.23 (1H, dq, 1=5.2, 6.9 Hz,1-1-6), 3.08 (1H, ddd, J=7.3, 5.5,4.1 Hz, H-13), 2.90 (1H, ddd, 0.1=6.6, 4.6, 4.1 Hz, H-12), 2.69 (3H, s, H-21), 2.52 (1H, dd, J=14.7, 10.1 Hz, H-2a), 2.44 (1H, bd, J=3.2 Hz, 7-OH), 2.41 (1H, dd, J=14.7, 3.5 Hz, H-2b), 2.10 (1H, ddd, J=15.0, 5.5, 3.2 Hz, H-14a), 1.90 (1H, ddd, J=15.0, 7.8, 7.3 Hz, H-14b), 1.711 (1H, m, H-8), 1.65 (1H, m, H-11a), 1.50 (1H, m, H-10a), 1.47 (1H, m, H-11b), 1.40(2K m, H-9), 1.39 (1H, m, H-10b), 1.33 (3H, s, H-2-3)), 1.16 (3H, d, J=6.9 Hz, H-24), 1.08 (3H, s, H-22), 0.98 (3H, d, J=7.0 Hz, H-25); 13C NMR (CDCl3, 75 MHz) δ 220.3 (s, C-5), 170.7 (s, C-1), 166.5 (s, C-20), 152.2 (s, C-18), 128.4 (d, C-16), 125.9 (d, C-17), 116.4 (d, C-19), 75.0 (d, C-7), 73.6 (d, C-3), 72.7 (d, C-15), 57.3 (d, C-12), 54.1 (d, C-13), 52.6 (s, C-4), 43.8 (d, C-6), 38.9 (t, C-2), 36.3 (d, C-8), 32.5 (t, C-14), 30.3 (t, C-9), 26.7 (t, C-11), 24.0 (t, C-10), 21.3 (q, C-23), 21.0 (q, C-22), 19.3 (q, C-21), 17.1 (q, C-25), 14.5 (q, C-24); EIMS m/z 479 [M]+ XXX; HRDCIMS m/z 480.2401 (calcd. for C25H38NO6S, 480.2401).

[0009] Epothilone A9 (8): colorless amorphous solid; [α]22D-37.6 (c 0.5, MeOH); UV (MeOH) λmax nm (ε) 211 (15500), 253 (14100); IR (KBr) νmax 3423, 2965, 2932, 2877, 1736, 1690, 1463, 1249, 1014, 979 cm−1; 1H NMR (CDCl3, 400 MHz) δ 7.10 (1H, s, H-19), 6.72 (1H, dd, J=10.7, 4.3 Hz, 27-OH), 6.60 (1H, bs, H-17), 5.69 (1H, dd, J=11.6, 2.0 Hz, H-15), 5.59 (1H, d, J=6.6 Hz, 3-OH), 4.49 (1H, ddd, J=12.9, 4.3, 1.2 Hz, H-27a), 4.27 (1H, ddd, J=11.6, 6.6, 2.9 Hz, H-3), 4.11 (1H, ddd, J=12.9, 10.7, 1.0 Hz, H-27b), 3.71 (1H, ddd, J=4.8, 3.0, 2.8 Hz, H-7), 3.17 (1H, dq, J=3.0, 6.8 Hz, H-6), 3.04 (1H, ddd, J=9.7, 3.6, 2.2 Hz, H-13), 2.93 (1H, bs, 70H), 2.91 (1H, ddd, J=9.7, 3.6, 2.7 Hz, H-12), 2.72 (3H, s, H-21), 2.48 (1H, dd, J=14.2, 11.6 Hz, H-2a), 2.11 (111, dd, J=14.2, 2.9 Hz, H-2b), 2.03 (1H, ddd, J=14.7, 2.2, 2.0 Hz, H-14a), 1.86 (1H, m, H-11a), 1.85 (1H, m, -H-14b), 1.79 (1H, m, H-8), 1.52 (1H, m, H-10a), 1.37 (3H, m, H-9 and H-10b), 1.37 (3H, s, H-23), 1.36 (1H, m, H-11 lb), 1.19 (3H, d, J=6.8 Hz, H-24), 1.02 (3H, d,.1=7.1 Hz, H-25), 1.00 (3H, s, H-22); 13C NMR (CDCl3, 75 MHz) δ 220.5 (s, C-5), 170.2 (s, C-1), 167.5 (s, C-20), 150.7 (s, C-18), 138.9 (s, C-16), 125.2 (d, C-17), 119.5 ((d, C19), 76.7 (d, C-15), 73.4 (d, C-7), 70.4 (d, C-3), 57.7 (d, C-12), 57.2 (t, C-27), 55.3 (d, C-13), 54.2 (s, C-4), 4i:3 (d, C-6), 40.7 (t, C-2), 37.5 (d, C-8), 31.8 (t, C-14), 31.2 (t, C-9), 28.0 (t, C11), 23.7 (q, C-23), 23.2 (t, C-10), 19.2 (q, C-21), 16.8 (q, C-22), 15.8 (q, C-25), 13.5 (q, C-24); EIMS m/z 509 [M]+ (9), 491 (4), 322 (28), 321 (25), 180 (45), 167 (40), 166 (100), 165 (49), 154 (47), 138 (33); HREIMS m/z 509.2467 (calcd. for C26H39NO7S, 509.2447).

[0010] Epothilone B10 (9): colorless amorphous solid; [α]22D-27 (c 0.15, MeOH); UV (MeOH) λmax 1M (g) 212 (15800), 247 (12500); IR (KBr) νmax 3434, 2962, 2930, 2876, 2858, 1733, 1692, 1461, 1259, 1052, 981 cm−1; 1H NMR (CDCl3, 600 MHz) δ 6.99 (1H, s, H-19), 6.60 (1H, bs, H-17), 5.42 (1H, dd, J=8.0, 3.0 Hz, H-15), 4.25 (1H, ddd, J=9.5, 6.3, 2.8 Hz, H-3), 4.23 (1H, bs, 3-OH), 3.77 (1H, ddd, J=4.0, 3.9, 3.8 Hz, H-7), 3.30 (1H, dq, J=4.0, 6.9 Hz, H6), 3.01 (2H, q, J=7.6 Hz, H-21), 2.81 (1H, dd, J=7.7, 4.6 Hz, H-13), 2.68 (1H, bs, 7-OH), 2.54 (1H, dd, J=13.9, 9.5 Hz, H-2a), 2.36 (1H, dd, J=13.9, 2.8 Hz, H-2b), 2.11 (1H, ddd, J=15.3, 4.6, 3.0 Hz, H-14a), 2.09 (3H, s, H-27), 1.91 (1H, ddd, J=15.3, 8.0, 7.7 Hz, H-14b), 1.74 (1H, m, H-8), 1.73 (1H, m, H-11a), 1.51 (1H, m, H-10a), 1.41 (1H, m, H-11 b), 1.39 (3H, t, J=7.6 Hz, H-28), 1.38 (3H, m, H-9 and H-10b), 1.37 (3H, s, H-23), 1.28 (3H, s, H-26),1.17 (3H, d, J=6.9 Hz, H-24), 1.09 (3H, s, H-22), 1.01 (3H, d, J=7.0 Hz, H-25); EIMS m/z 521 [M]+ (22), 449 (7), 350 (18), 334 (57), 248 (16), 234 (27), 196 (41), 182 (59), 180 (96), 178 (100), 166 (44), 154 (44); HREIMS m/z 521.2808 (calcd. for C28H43NO6S, 521.2811).

[0011] Epothilone G1 (10): colorless amorphous solid; [α]22D-39.7 (c 1.0, MeOH); UV (MeOH) λmax nm (ε) 203 (15200), 236 (15100); IR(KBr) νmax3456, 2962, 2933, 2876, 1736, 1691, 1585, 1466, 1262, 980 cm−1; 1H NMR (CDCl3, 400 MHz) δ 7.47 (1H, s, H-19), 6.33 (1H, bs, H-17), 5.42 (1H, dd, J=8.3, 2.9 Hz, H-15), 4.11 (1H, ddd, J=10.1, 6.1, 3.4 Hz, H-3), 3.78 (1H, bddd, J=5.2, 3.5, 3.5 Hz, H-7), 3.63) (1H, bd, J=6.1 Hz, 3-OH), 3.21 (1H, dq, J=5.2, 7.0 Hz, H-6), 3.00 (1H, ddd, J=7.7, 4.8, 4.2 Hz, H-13), 2.88 (1H, ddd, J=7.1, 4.2, 4.2 Hz, H12), 2.53 (1H, dd, J=14.8, 10.1 Hz, H-2a), 2.51 (1H, bd, J=3.5 Hz, 7-OH), 2.43 (1H, dd, J=14.8, 3.4 Hz, H-2b), 2.43 (3H, s, H-21), 2.07 (1H, ddd, J=15.1, 4.8, 2.9 Hz, H-14a), 1.99 (3H, d, J=1.3 Hz, H-27), 1.86 (1H, ddd, J=15.1, 8.3, 7.7 Hz, H-14b), 1.71 (1H, m, H-8), 1.69 (1H, m, H-1 la), 1.53 (1H, m, H-10a), 1.42 (1H, m, H-1 ib), 1.40 (3H, m, H-9 and H-10b), 1.34 (3H, s, H-23), 1.16 (3H, d, J=7.0 Hz, H-24), 1.09 (3H, s, H-22), 0.99 (3H, d, J=6.9 Hz, H25); 13C NMR, (CDCl3, 100 MHz) δ 220.1 (s, C-5), 170.5 (s, C-1), 161.0 (s, C-20), 1374 (s, C18), 136.7 (s, C-16), 135.9 (d, C-19), 116.4 (d, C-17), 76.4 (d, C-15), 74.9 (d, C-7), 73.7 (d, C3), 57.4 (d, C-12), 54.4 (d, C-13), 52.6 (s, C-4), 43.8 (d, C-6), 38.8 (t, C-2),″) 6.2 (d, C-8), 31.4 (t, C-14), 30.4 (t, C-9), 27.0 (t, C-11), 23.9 (t, C-10), 21.3 (q, C-23), 21.2 (q, C-22), 17.2 (q, C25), 15.8 (q, C-27), 14.4 (q, C-24), 13.8 (q, C-21); EIMS m/z 477 [M]+ (4), 405 (7), 290 (40), 152 (39), 150 (100), 14S (23), 124 (23); HREIMS m/z 477.2684 (calcd. for C26H39NO7, 477.2727).

[0012] Epothilone G2 (11): colorless amorphous solid; [α]22D-22.6 (c 1.0, MeOH); W (MeOH) λmax nm (ε) 202 (21500), 236 (14800); IR (KBr) νmax3456, 2965, 2934, 2877, 1737, 1690, 1586, 1464, 1250, 980 cm−1; 1H NMR (CDCl3, 400 MHz) δ 7.48 (1H, s, H-19), 6.33 (1H, bs, H-17), 5.43 (IF, dd, J=7.1, 3.6 Hz, H-15), 4.12 (1H, ddd, J=9.9, 6.4, 3.4 Hz, H-3), 3.77 (1H, ddd, J=4.7, 4.4, 4.1 Hz, H-7), 3.83 (1H, bd, J=6.4 Hz, 3-OH), 3.30 (1H, dq, J=4.7, 6.9 Hz, H-6), 2.78 (1H, dd, J=7.0, 5.4 Hz, H-13), 2.54 (1H, dd, J=14.3, 9.9 Hz, H-2a), 2.51 (1H, bd, J=4.1 Hz, 7-OH), 2.44 (3H, s, H-21), 2.40 (1H, dd, J=14.3, 3.4 Hz, H-2b), 2.03 (1H, ddd, J=15.2, 5.4, 3.611z, H-14a), 2.00 (3H, d, J=1.3 Hz, H-27), 1.92 (1H, ddd, J=15.1, 7.1, 7.0 Hz, H-14b), 1.71 (1H, m, H-8), 1.68 (1H, m, H-11a), 1.51 (1H, m, H-10a), 1.42 (1H, M, H-11b), 1.39 (3H, m, H-9 and H-10b), 1.35 (3H, s, H-23), 1.26 (3H, s, H-26), 1.16 (3H, d, J=6.9 Hz, H-24), 1.07 (3H, s, H-22), 0.99 (3H, d, J=7.0 Hz, H-25); 13CNMR (CDCl3, 100 MHz) δ 220.7 (s, C-5), 170.5 (s, C-1), 161.0 (s, C-20), 137.4 (s, C-18), 136.5 (s, C-16), 135.9 (d, C-19), 116.3 (d, C-17), 76.6 (d, C-15), 74.6 (d, C-7), 73.5 (d, C-3), 61.3 (s, C-12), 61.1 (d, C-13), 52.7 (s, C4), 43.4 (d, C-6), 39.0 (t, C-2), 36.5 (d, C-8), 32.0 (t, C-1), 31.8 (t, C-14), 30.8 (t, C-9), 22.8 (t, C-10), 22.9 (q, C-26), 21.0 (q, C-23), 20.8 (q, C-22), 17.2 (q, C-25), 15.9 (q, C-27), 14.1 (q, C-24), 13.8 (q, C-21); EIMS m/z 491 [M]+ (21), 419 (6), 320 (18), 304 (39), 166 (42), 152 (57), 150 (100), 149 (44), 148 (58), 124 (35), 109 (33); HREIMS m/z 491.2878 (calcd. for C27H41NO7, 491.2883).

[0013] Epothilone H1 (12): colorless amorphous solid; [α]22D-84.2 (c 0.2, MeOH); WV (MeOH) λmax nm (ε) 203 (19600), 237 (12000); IR (KBr) νmax3436, 2933, 2880, 2860, 1734, 1688, 1585, 1251, 1007 cm−1; 1H NMR(CDCl3, 400 MHz) δ 7.47 (1H, s, H-19), 6.31 (1H, bs, H-17), 5.43 (1H, ddd, J=10.6, 10.2, 4.5 Hz, H-12), 5.36 (1H, dddd, J=10.6, 9.6, 5.0, 1.3 Hz, H-13), 5.30 (1H, dd, J=9.9, 2.0 Hz, H-15), 4.16 (1H, ddd, J=11.2, 5.3, 2.8 Hz, H-3), 3.73 (1H, ddd, .I=3.9, 2.5, 2.3 Hz, H-7), 3.12 (1H, dq, J=2.3, 6.9 Hz, H-6), 2.92 (1H, d, J=2.5 Hz, 7-OH), 2.91 (1H, d, J=5.3 Hz, 7-OH), 2.66 (1H, ddd, J=15.1, 9.9, 9.6 Hz, H-14a), 2.50 (1H, dd, J=15.4, 11.2 Hz, H-2a), 2.43 (3H, s, H-21), 2.37 (1H, dd, J=15.4, 2.8 Hz, H-2b), 2.23 (1H, m, H-14b), 2.18 (1H, m, H-11a), 2.01 (1H, m, H-11b), 2.08 (3H, d, J=1.3 Hz, H-27), 1.74 (1H, m, H-8), 1.65 (1H, m, H-10a ), 1.33 (1H, m, H-9a), 1.31 (3H, s, H-23), 1.19 (1H, m, H-10b), 1.18 (1H, m, H-9b), 1.17 (3H, d, J=6.9 Hz, H-24), 1.08 (3H, s, H-22), 0.99 (3H, d, J=7.1 Hz, H-25);13C NMR, see Table 1; EMS m/z 461 [M]+ (6), 310 (5), 274 (10), 273 (7), 171 (63), 152 (100), 148 (18), 111 (15); HREIMS m/z 461.2743 (calcd. for C26H39NO6, 461.2777).

[0014] Epothilone H2 (13): colorless amorphous solid; [α]22D -44.4 (c 0.25, MeOH); UV (MeOH) λmax nm (ε) 203 (14500), 236 (12200); IR (KBr) νmax. 3436, 2967, 2935, 2880, 1734, 1690, 1586, 1251, 1007 cm−1; 1H NMR (CDCl3, 400 MHz) δ 7.46 (1H, s, H-19), 6.30 (1H, bs, H-17), 5.23 (1H, dd, J=9.8, 2.1 Hz, H-15), 5.12 (1H, dd, J=10.1, 5.3 Hz, H-13), 4.20 (1H, ddd, J=10.8, 5.7, 2.9 Hz, H-3), 3.71 (1H, ddd, J=3.8, 2.6, 2.6 Hz, H-7), 3.14 (1H, dq, J=2.6, 6.9 Hz, H-6), 2.93 (d, J=5.7 Hz, 3-OH), 2.90 (1H, bd, J=2.6 Hz, 7-OH), 2.62 (1H, ddd, J=15.1, 9.8, 9.8 Hz, H-14a), 2.46 (1H, dd, J=15.1, 10.8 Hz, H-2a), 2.43 (3H, s, H-21), 2.32 (1H, dd, J=15.1, 2.9 Hz, H-2b), 2.29 (1H, m, H-11a), 2.19 (1H, bd, J=15.1 Hz, H-14b), 1.97 (3H, d, J=1.3 Hz, H-27), 1.87 (1H, m, H-1 lb), 1.73 (1H, m, H-8), 1.67 (1H, m, H-10a ), 1.65 (3H, bs, H-26), 1.32 (3H, s, H-23), 1.26 (2H, m, H-9), 1.24 (1H, m, H-10b), 1.18 (3H, d, J=6.9 Hz, H-24), 1.07 (3H, s, H-22), 1.00 (3H, d, J=7.0 Hz, H-25); 13C NMR (CDCl3, 100 MHz) δ 220.6 (s, C-5), 170.3 (s, C-1), 161.0 (s, C-20), 138.6 (s, C-12), 138.4 (s, C-16), 137.5 (s, C-18), 135.6 (d, C-19), 120.8 (d, C-13), 115.8 (d, C-17), 78.9 (d, C-15), 74.3 (d, C-7), 72.7 (d, C-3), 53.3 (s, C-4), 42.0 (d, C-6), 39.6 (t, C-2), 38.6 (d, C-8), 32.4 (t. C-14), 31.9 (t, C-9), 31.6 (t, C-Il), 25.6 (t, C-10), 23.0 (q, C-26), 22.8 (q, C-23), 18.8 (q, C-22), 16.1 (q, C-27), 15.9 (q, C-25), 13.8 (q, C-21), 13.6 (q, C-24); EIMS m/z 475 [M]+ (11), 288 (9), 287 (5), 188(7), 171 (32), 152 (100), 111 (10); HREIMS m/z 475.2913 (calcd. for C27H41NO6, 475.2934).

[0015] Epothilone C1 (16): colorless amorphous solid; [α]22D -114.0 (c 10.0, MeOH); UV (MeOH) λmax nm (ε) 211 (16500), 248 (12500); IR (KBr) νmax3440, 2933, 2877, 2858, 1730, 1708, 1457, 1244, 981 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.96 (1H, s, H-19), 6.56 (1H, bs, H-17), 5.47 (1H, dd, J=9.2, 3.0 Hz, H-15), 5.43 (1H, m, H-12), 5.40 (1H, m, H-13), 4.40 (1H, ddd, J=6.2, 6.1, 6.1 Hz, H-3), 3.69 (1H, dd, J=5.7, 3.6 Hz, H-7), 3.01 (1H, dq, J=5.7, 6.9 Hz, H-6), 3.01 (1H, bs, 3-OH), 2.84 (1H, dq, J=5.2, 7.0 Hz, H-4), 2.68 (3H, s, H-21), 2.66 (1H, ddd,.1=16.4, 9.2, 7.3 Hz, H-14a), 2.64 (1H, dd, J=15.9, 7.1 Hz, H-2a), 2.54 (1H, dd, J=15.9, 6.1 Hz, H-2b), 2.38 (1H, bd, J=16.4 Hz, H-14b), 2.35 (1H, bs, 7-OH), 2.07 (3H, bs, H-27), 2.03 (2H, m, H-i 1), 1.62 (1H, m, H-10a), 1.53 (1H, m, H-8), 1.35 (1H, m, H-9a), 1.22 (1H, M, H-9b), 1.19 (3H, d, J=6.9 Hz, H-24), 1.14 (3H, d, J=6.9 Hz, H-23), 1.10 (1H, m, H-10b), 0.95 (3H, d, J=6.9 Hz, H-25); 13C NMR, see Table 1; EIMS m/z 463 [M]+ (5), 324 (8), 290 (8), 204 (7), 168 (100), 164 (15), 139 (36); HREIMS m/z 463.2381 (calcd. for C23H37NO5S, 463.2392).

[0016] Epothilone D1 (17): colorless amorphous solid; [α]22D -118.6 (c 0.5, MeOH); UV (MeOH) λmax n-m (ε) 208 (18300), 249 (11900); IR (KBr) νmax3439, 2965, 2934, 2877, 1729, 1707, 1456, 1250, 980 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.98 (1H, s, H-19), 6.56 (1H, bs, H-17), 5.51 (1H, dd, J=9.5, 3.4 Hz, H-15), 5.16 (1H, dd, J=8.0, 4.2 Hz, H-13), 4.42 (1H, ddd, J=7.1, 6.3, 5.5 Hz, H-3), 3.70 (1H, dd, J=6.5, 2.9 Hz, H-7), 3.07 (1H, dq, J=6.5, 6.9 Hz, H-6), 2.95 (1H, dq. J=4.7, 7.0 Hz, H-4), 2.71 (3H, s, H-21), 2.69 (1H, dd, J=16.0, 6.3 Hz, H-2a), 2.64 (1H, m, H-14a), 2.59 (1H, dd, J=16.0, 7.1 Hz, H-2b), 2.46 (1H, bs, 3-OH), 2.38 (1H, bd, J=16.0 Hz, H-14b), 2.19 (1H, ddd, J=13.3,8.6,5.7 Hz,H-11a), 2.10(3H, d, J=1.4 Hz, H-27), 2.02 (1H, bs, 7-OH), 1.91 (1H, ddd, J=13.3, 6.0, 6.0 Hz, H-1 lb), 1.68 (1H, m, H-10a ), 1.66 (3H, bs, H-26), 1.53 (1H, m, H-8), 1.37 (1H, m, H-9a), 1.26 (1H, m, H-9b), 1.24 (3H, d, J=6.9 Hz, H-24), 1.19 (1H, m, H-10b), 1.14 (3H, d. J=7.0, H-23), 0.99 (3H, d, J=6.9 Hz, H-25); 13C NMR (CDCl3, 100 MHz) δ 217.0 (s, C-5), 169.7 (s, C-1), 165.0 (s, C-20), 152.2 (s, C18), 1-38.5 (s, C-12), 137.7 (s, C-16), 120.7 (d, C-13), 120.1 (d, C-17), 116.3 (d, C-19), 78.8 (d, C-15), 77.2 (d, C-7), 67.7 (d, C-3), 52.1 (d, C-4), 46.5 (d, C-6), 40.6 (t, C-2), 37.6 (d, C-8), 32.3 (t, C-14), 31.8 (t, C-11), 29.5(t, C-9), 25.5 (t, C-10), 23.1 (q, C-26), 19.2 (q, C-21), 15.5 (q, C27), 16.6 (q, C-25), 14.5 (q, C-24), 9.7 (q, C-23); EIMS m/z 477 [M]+ (13), 304 (19), 303 (31), 218 (40), 204 (41), 168 (100), 164 (45), 157 (25), 139 (18); HREIMS m/z 477.2544 (calcd. for C26H39NO5S, 477.2549).

[0017] Epothilone C2 (18): colorless amorphous solid; [α]22D -11.6 (c 10.0, MeOH); UV (MeOH) λmax nm (ε) 212 (15500), 249 (12100); IR (KBr) νmax3428, 2962, 2929, 2877, 2859, 1734, 1705, 1460, 1251, 9S2 cm−1;1H NM (CDCl3, 300 MHz) δ 6.99 (1H, s, H-19), 6.66 (1H, bs, H-17), 5.55 (1H, ddd, J=10.4, 9.2, 6.1 Hz, H-12), 5.38 (1H, ddd, J=10.4, 9.3, 6.2 147, H-13), 5.22 (1H, dd, J=8.8, 2.8 Hz, H-15), 4.42 (1H, dddd, J=9.4, 5.6, 4.2, 4.1 Hz, H-3), 3.93 (1H, d, J=5.6 Hz, 3-OH), 3.86 (1H, m, H-7), 3.15 (1H, bs, 7-OH), 3.12 (1H, dq, J=4.2, 7.0 Hz, H-4), 3.00 (1H, dq, J=6.9, 7.0 Hz, H-6), 2.70 (3H, s, H-21), 2.62 (1H, dddd, J=15.1, 9.3, 8.8, 0.8 Hz, H-14a), 2.58 (1H, dd, J=15.4, 9.4 Hz, H-2a), 2.38 (1H, dd, J=15.4, 4.1 Hz, H-2b), 2.31 (1H, ddd,.1=15.1, 6.2, 2.8 Hz, H-14b), 2.08 (3H, d, J=1.3 Hz, H-27), 2.15 (1H, m, H-11a), 2.04 (1H, m, H-11b), 1.71 (1H, m, H-8), 1.59 (1H, m, H-10a), 1.43 (1H, m, H-9a), 1.31 (114, m, H-9b), 1.26 (3H, d, J=7.0 Hz, H-24), 1.15 (3H, d, J=7.0 Hz, H-23), 1.11 (1H, m, H-10b), 1.00 (3H, d, J=6.9 Hz, H-25); 13C NMR, see Table 1; EIMS m/z 463 [M]+ (7), 324 (7), 306 (8), 290 (17), 168 (100), 164 (14), 139 (27); HREIMS m/z 463.2392 (calcd. for C25H37NO5S, 463.2392).

[0018] Epothilone D2 (19): colorless amorphous solid; [α]22D -12.5 (c 1.0, MeOH); UV (MeOH) λmax nm (ε) 210 (15400), 248 (11200); IR (KBr) νmax 3436, 2965, 2930, 2877, 1732, 1705, 1458, 1253, 980 cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.97 (1H, s, H-19), 6.56 (1H, bs, H-17), 5.18 (IF, dd, J=7.9, 4.9 Hz, H-15), 5.18 (1H, ddd, J=9.6, 5.4, 1.0 Hz, H-13), 4.27 (1H, m, H-3), 3.88 (1H, dd, J=5.6, 4.6 Hz, H-7), 3.19 (1H, bs, 3-OH), 3.07 (1H, dq, J=4.3, 7.0 Hz, H-4), 2.95 (1H, dq, J=5.6, 7.0 Hz, H-6), 2.70 (3H, s, H-21), 2.62 (1H, dd, J=14.9, 7.8 Hz, H-2a), 2.56 (1H, ddd, J=14.7, 9.6, 7.9 Hz, H-14a), 2.43 (1H, dd, J=14.9, 5.6 Hz, H-2b), 2.38 (1H, bs, 7-OH), 2.26 (1H, ddd, J=14.5, 5.4, 4.9 Hz, H-14b), 2.19 (1H, ddd, J=13.0, 10.4, 5.4 Hz, H-11a), 2.10 (3H, d, 0.1=1.4 Hz, H-27), 1.95 (1H, ddd, J=13.0, 10.3, 5.3 Hz, H-11b), 1.72 (1H, m, H—S), 1.68 (3H, bs, H-26), 1.61 (1H, m, H-10a ), 1.39 (2H, m, H-9), 1.21 (1H, m, H-10b), 1.19 (3H, d, J=6.9 Hz, H-24),1.17 (3H, d. J=7.0, H-22),1.00 (3H, d, J=6.9 Hz, H-25J; 13C NMR (CDCl3, 100 MHz) δ 216.8 (s, C-5), 170.4 (s, C-1), 164.9 (s, C-20), 152.3 (s, C-18), 139.8 (s, C-12), 137.5 (s, C-16), 120.5 (d, C-17), 119.2 (d, C-13), 116.3 (d, C-19), 80.0 (d, C-15), 74.3 (d, C-7), 69.7 (d, C-3), 48.6 (d, C-4), 48.4 (d, C-6), 39.9 (t, C-2), 36.6 (d, C-8), 32.2 (t, C-14), 32.7 (t, C-11), 30.9 (t, C-9), 26.0 (t, C-10), 23.6 (q, C-26), 19.2 (q, C-21), 15.4 (q, C-27), 17.1 (q, C-25), 12.4 (q, C-24), 12.7 (q, C-23); EIMS m/z 477 [M]+ (22), 304 (19), 303 (17), 218 (22), 204 (25), 163 (100), 164 (28), 157 (31), 139 (21); HREIMS m/z 477.2545 (calcd. for C26H39NO5S, 477.2549).

[0019] Epothilone C3 (20): colorless amorphous solid; [α]22D -62.1 (c 5.0, MeOH); UV (MeOH))λmax nm (ε) 212 (16200), 248 (12300); IR (KBr) νmax 3432, 2928, 2878, 2858, 1736, 1698, 1252, 1040 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.95 (1H, s, H-19), 6.56 (1H, bs, H-17), 5.44 (1H, ddd, J=10.9, 10.3, 5.4 Hz, H-12), 5.33 (1H, ddd, J=10.9, 9.3, 4.6 Hz, H-13), 5.23 (1H, dd, J=9.5, 2.2 Hz, H-15), 4.36 (1H, ddd, J=11.3, 5.6, 2.3 Hz, H-3), 4.04 (1H, d, J=5.6 Hz, 3-OH), 3.93 (1H, ddd,.1=9.5, 2.3, 1.4 Hz, H-7), 3.56 (1H, bd, J=2.3 Hz, 7-OH), 2.70 (1H, dd, J=18.0, 1.4 Hz, H-6a), 2.67 (3H, s, H-21), 2.61 (1H, ddd, J=15.3, 9.5, 9.3 Hz, H-14a), 2.38 (1H, dd,.1=14.3, 11.3 Hz, H-2a), 2.36 (1H, dd, J=18.0, 9.5 Hz, H-6b), 2.28 (1H, bd, J=15.3 Hz, H-14b), 2.12 (1H, m, H-11a), 2.06 (1H, dd, J=14.3, 2.3 Hz, H-2b), 2.03 (3H, d, J=1.3 Hz, H-27),1.96 (1H, m, H-1 lb), 1.75 (1H, m, H-8), 1.54 (1H, m, H-10a), 1.26 (1H, m, H-9a), 1.25.(3H, s, H-23), 1.17 (1H, m, H-10b), 1.15 (1H, m, H-9b), 1.03 (3H, s, H-22), 0.91 (3H, d. J=6.8 Hz, H-25); 13C NMR, see Table 1; EIMS m/z 463 [M]+ (28), 290 (14), 168 (100), 164 (36), 157 (44). 151 (25), HREIMS m/z 463.2379 (calcd. for C25H37NO5S, 463.2392).

[0020] Epothilone C4 (21): colorless amorphous solid; [α]22D -75.6 (c 1.0, MeOH); UV (MeOH) λmax nm (ε) 212 (17200), 248 (12500); IR (KBr) νmax 3434, 2974, 2932, 2859, 1735, 1686, 1252, 1046 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.96 (1H, s, H-19), 6.60 (1H, bs, H-17), 5.43 (1H, m, H-12), 5.40 (1H, m, H-13), 5.26 (1H, dd, J=9.6, 2.3 Hz, H-15), 4.41 (1H, ddd, J=11.4, 5.8,2.5 Hz, H-3), 3.78 (1H, m, H-7), 3.70 (1H, bs, 3-OH), 3.46 (1H, d, J=0.9 Hz, 7-OH), 3.01 (1H, dq, J=0.5, 7.0 Hz, H-6), 2.69 (3H, s, H-21), 2.66 (1H, ddd, J=15.3, 9.6, 8.8 Hz, H-14a), 2.47 (1H, dd, J=14.5, 11.4 Hz, H-2a), 2.29 (1H, m, H-1.4b), 2.25 (1H, dd, J=14.5, 2.5 Hz, H-2b), 2.24 (1H, m, H-11a), 2.07 (3H, d, J=1.4 Hz, H-27), 1.96 (1H, m, H-11b), 1.51 (2H, m, H-8), 1.44 (2H, m, H-10), 1.37 (2H, m, H-9), 1.32 (3H, s, H-23), 1.17 (3H, d, J=7.0 Hz, H-24), 1.07 (3H, s, H-22); 13C NMR , see Table 1; EIMS m/z 463 [M]+ (7), 276 (15), 171 (33), 168 (100), 164 (23), 151 (22), 111 (13); HREIMS m/z 463.2373 (calcd. for C25H37NO5S, 463.2392).

[0021] Epothilone C5 (22): colorless amorphous solid; [α]22D -158.2 (c 0.5, MeOH); UV (MeOH) λmax nm (ε) 205 (19500), 247 (12700); IR (KBr) νmax. 3447, 2972, 2927, 1737, 1690, 1450,1252,1181, 936 cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.93 (1H, s, H-19), 6.48 (1H, bs, H-17), 5.48 (1H, ddd,. J=10.7, 6.2, 6.2 Hz, H-12), 5.39 (1H, m, H-13), 5.37 (1H, M, H-9), 5.34 (1H, dd, J=8.0, 2.3 Hz, H-15), 4.29 (1H, dd, J=6.0, 2.6 Hz, H-7), 4.09 (1H, ddd, J=10.8, 7.1, 2.9 Hz, H-3), 3.59 (1H, d, J.=7.1 Hz, 3-OH), 3.17 (1H, dq, J=6.0, 6.9 Hz, H-6), 2.68 (3H, s, H-21).2.54 (1H, ddd, J=15.2, 8.1, 8.0 Hz, H-14a), 2.44 (1H, bs, 7-OH), 2.42 (1H, dd, J=15.1, 2.9 Hz, H-2a), 2.41 (1H, ddd, J=15.2, 2.3, 2.3 Hz, H-14b), 2.34 (1H, dd, J=15.1, 10.8 Hz, H2b), 2.20 (1H, m, H-10a ), 2.18 (2H, m, H-11), 2.12 (1H, m, H-10b), 2.06 (3H, bs, H-27), 1.67 13 (3H, bs, H-25), 1.27 (3H, s, H-23), 1.21 (3H, d, J=6.9 Hz, H-24), 1.15 (311, s, H-22); 13C NMR, see Table 1; EIMS m/z 475 [M]+ (6), 392 (7), 304 (6), 288 (33), 204 (76), 171 (19), 168 (100), 164 (12); REIMS m/z 475.2380 (calcd. for C26H37NO5S, 475.2392).

[0022] Epothilone D5 (23): colorless amorphous solid; [α]22D -150 (c 0.2, MeOH); UV (MeOH)) λmax nm (ε) 205 (23300), 248 (13600); IR (KBr) νmax 3439, 2967, 2927, 1736, 1690, 1451, 1254, 1181, 987 cm−1; 1H NMR (CDCl3, 400 MHz) 5; 6.94 (1H, s, H-19), 6.51 (1H, bs, H-17), 5.34 (1H, bs, H-9), 5.29 (1H, dd, J=8.0, 2.4 Hz, H-15), 5.16 (1H, dd, J=8.2, 6.2 Hz, H-13), 4.30 (1H, bd, J=4.9 Hz, H-7), 4.19 (1H, ddd, J=10.8, 7.6, 3.0 Hz, H-3), 3.68 (1H, d, J=7.6 Hz, 3-OH), 3.17 (1H, dq, J=4.9, 7.0 Hz, H-6), 2.69 (3H, s, H-21), 2.65 (1H, d, J=2.1 Hz, 7-OH), 2.56 (1H, ddd, J=16.2, 8.2, 8.0 Hz, H-14a), 2.40 (1H, dd, J=15.0, 3.0 Hz, H-2a), 2.39 (1H, bd, J=16.2 Hz, H-14b), 2.34 (1H, dd, J=15.0, 10.8 Hz, H-2b), 2.25 (2H, m, H-10a and H-11a), 2.20(1H, m, H-10b), 2.17 (1H, m, H-11b), 2.05 (3H, d, J=1.0 Hz, H-27), 1.69 (3H, bs, H-25), 1.68 (3H, bs, H-26), 1.29 (3H, s, H-23), 1.23 (3H, d, J=7.0 Hz, H-24), 1.16 (3H, s, H-22); 13C NMR, see Table 1; EIMS m/z 489 [M]+ (4), 406 (4), 338 (7), 302 (13), 218 (35), 171 (10), 168 (100), 153 (20), 125 (10); HREIMS m/z 489.2536 (calcd. for C27H39NO5S, 489.2549).

[0023] Epothilone C6 (24): colorless amorphous solid; [α]22 D -205.2 (c 1.0, MeOH); UV (MeOH) λmax nm (ε) 218 (24600), 237 (28800); IR (KBr) νmax 3435, 2967, 2927, 2882, 1732, 1688, 1465, 1258, 988 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.97 (1H, s, H-19), 6.58 (1H, bs, H-17), 6.43 (1H, dd, 15.5, 10.8 Hz, H-11), 6.11 (1H, dd, J=10.8, 10.6 Hz, H-12), 5.75 (1H, ddd, J.=15.5,8.3,5.6 Hz, H-10), 5.34 (1H, m, H-13), 5.34 (1H, dd, J=9.7, 2.4 Hz, H-15), 4.16 (1H, ddd, .J=9.2, 4.9, 4.3 Hz, H-33), 3.74 (1H, ddd, J=2.2, 2.1, 1.7 Hz, H-7), 3.24 (1H, dq, J=2.1, 6.9 Hz, H-6), 3.06 (1H, d, J=2.2 Hz, 7-OH), 2.93 (1H, d, J=4.9 Hz, 3-OH), 2.78 (1H, dddd, J=14.1, 9.9 9.7, 0.7, H-14a), 2.71 (3H, s, H-21), 2.48 (1H, m, H-9a), 2.47 (1H, dd, J=15.5, 9.2 Hz, H-2a), 2.40 (1H, dd, J=15.5, 4.3 Hz, H-2b), 2.38 (1H, bdd, J=14.1, 7.8 Hz, H-14b), 2.11 (3H, d, J=1.3 Hz, H-27), 1.96 (1H, m, H-8), 1.33 (3H, s, H-23), 1.11 (3H, d, J=6.9 Hz, H-24), 1.06 (3H, s, H-22), 1.05 (3H, d, J=6.8 Hz, H-25); 13C NMR, see Table 1; EIMS m/z 475 [M]+ (13), 387 (2), 316 (4), 288 (15), 230 (16), 204 (9), 171 (18), 168 (100), 164 (14), 151 (17); HREIMS m/z 475.2361 (calcd. for C26H37NO5S, 475.2392).

[0024] Epothilone C7 (25): colorless amorphous solid; [C]22D -XXX (c 2.0, MeOH); UV (MeOH) λmax nm (ε) XXX (XXX), XXX (XXX); IR (KBr) νmax XXX cm−1; 1H NMR (CDCl3, 400 MHz) δ 7.01 (1H, s, H-19), 6.66 (1H, bs, H-17), 5.59 (1H, ddd, J=11.1, 11.1, 3.8 Hz, H-12), 5.40 (1H, dd, J=11.1, 9.2, H-13), 5.03 (1H, d, J=9.3 Hz, H-15), 4.62 (1H, dd, J=9.3, 9.2 Hz, H-14), 4.18 (1H, bd, J=11.0 Hz, H-3), 3.72 (1H, bs, H-7), 3.20 (1H, bs, 3-OH), 3.09 (1H, dq, J=1.9, 6.8 Hz, H-6), 3.00 (1H, bs, 7-OH), 2.69 (3H, s, H-21), 2.47 (1H, dd, J=14.8, 11.0 Hz, H-2a), 2.32 (1H, dd, J=14.8, 2.6 Hz, H-2b), 2.27 (1H, m, H-11a), 2.19 (3H, bs, H-27), 2.13 (1H, m, H-11b), 1.76 (1H, m, H-8), 1.70 (1H, m, H-10a ), 1.35 (1H, m, H-9a), 1.32 (3H, s, H-23), 1.23 (1H, m, H-9b), 1.21 (1H, m, H-10b), 1.18 (3H, d, J=6.8 Hz, H-24), 1.08 (3H, s, H-22), 1.00 (3H, d,.]=6.9 Hz, H-25); EIMS m/z 493 [M]+XXX; HREIMS m/z 493.XXX (calcd. for C26H39NO6S, 493.2498).

[0025] Epothilone C9 (26): colorless amorphous solid; [α]22D -75.2 (c 2.5, MeOH); UV (MeOH) λmax nm (ε) 210 (16803), 248 (17800); IR (KBr) νmax 3443, 2932, 2881, 1734, 1689, 1465, 1255,1183, 976 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.93 (1H, s, H-19), 6.62 (1H, dd, J=15.6, 0.6 Hz, H-17), 6.49 (1H, dd, J=15.6, 6.6 Hz, H-16), 5.52 (1H, dddd, J=9.5, 6.6, 2.8, 0.6 Hz, H-15), 5.42 (1H, m, H-12), 5.41 (1H, m, H-13), 4.13 (1H, ddd, J=11.0, 5.3, 2.8 Hz, H-3), 3.69 (1H, ddd, J=3.7, 2.8, 2.5 Hz, H-7), 3.11 (1H, dq, J=2.5, 6.8 Hz, H-6), 2.95 (1H, d, J=5.3 Hz, 3-OH), 2.90 (1H, d, J=2.8 Hz, 7-OH), 2.69 (3H, s, H-21), 2.67 (1H, ddd, 0.1=14.9, 9.5, 8.4 Hz, H-14a), 2.48 (1H, dd, J=15.6, 11.0 Hz, H-2a), 2.33 (1H, dd, J=15.6, 2.8 Hz, H-2b), 2.30 (1H, bd, J=14.9 Hz, H-14b), 2.14 (1H, m, H-11a), 2.03 (1H, m, H-11b), 1.71 (1H, m, H-8), 1.63 (1H, m, H-10a ), 1.31 (1H, m, H-9a), 1.29 (3H, s, H-23), 1.17 (3H, d, J=6.8 Hz, H-24), 1.16 (1H, m, H-10b), 1.14 (1H, m, H-9b), 1.05 (3H, s, H-22), 0.97 (3H, d, J=7.1 Hz, H-25); 13C NMR, see Table 1; EIMS m/z 463 [M]+ (21), 310 (10), 276 (21), 171 (83), 154 (100), 150 (27), 111 (18); HREIMS m/z 463.2382 (calcd. for C25H37NO5S, 463.2392).

[0026] Epothilone C9, (27): colorless amorphous solid; [α]22D-93.4 (c 1.0, MeOH); UV (MeOH) λmax nm (ε) 209 (15200), 254 (15700); IR (KBr)) νmax 3416, 2966, 2932, 1736, 1689, 1463, 1249, 1011 cm−1; 1H NMR (CDCl3, 400 MHz) δ 7.06 (1H, s, H-19), 6.65 (1H, bs, H-1 7), 6.56 (1H, dd, J=10.6, 4.4 Hz, 27-OH), 5.55 (1H, d, J=6.2 Hz, 3-OH), 5.52 (1H, dd, J=11.6, 2.0 Hz, H-15), 5.44 (1H, dddd, J=11.2, 10.7, 3.1, 1.7 Hz, H-12), 5.35 (1H, dddd, J=11.0, 10.7, 3.9, 1.7 Hz, H-13), 4.47 (11-1, ddd, J=12.5, 4.4, 1.3 Hz, H-27a), 4.35 (1H, ddd, J=11.7, 6.2, 2.6 Hz, H-3), 4.20 (1H, ddd, J=12.5, 10.6, 0.9 Hz, H-27b), 3.63 (1H, ddd, J=4.6, 1.8, 0.9 Hz, H-7), 3.24 (1H, d, J=1.8 Hz, 7-OH), 3.13 (1H, dq, J=0.9, 6.8 Hz, H-6), 2.80 (1H, ddd, J=14.8, 11.6, 11.0 Hz, H-14a), 2.71 (3H, s, H-21), 2.40 (1H, dd, J=14.4, 11.7 Hz, H-2a), 2.24 (1H, m, H I 1a), 2.06 (1H, dd, J=14.4, 2.6 Hz, H-2b), 2.01 (1H, ddd; J=14.8, 3.9, 2.0 Hz, H-14b), 2.00 (1H, m, H-1 lb), 1.77 (1H, m, H-8), 1.69 (1H, m, H-10a ), 1.35 (1H, m, H-9a), 1.35 (3H, s, H 23), 1.19 (1H, m, H-10b), 1.19 (3H, d, J=6.8 Hz, H-24), 1.18 (1H, m, H-9b), 1.01 (3H, d, J=7.1 Hz, H-25), 0.98 (3H, H-22); 13C NMR, see Table 1; EIMS m/z 493 [M]+ (17), 306′(64), 184 (50), 171 (30), 167 (38), 166 (100), 138 (12); HREIMS m/z 493.2502 (calcd. for C26H39NO6S, 493.2498).

[0027] trans-Epothilone C1, (28): colorless amorphous solid; [α]22D -84 (c 0.2, MeOH); UV (MeOH) λmax nm (ε) 211 (17400), 248 (12900);1R (KBr) νmax 3433, 2961, 2933, 2879, 1730, 1708, 1457, 1251, 975 cm−1; 1H NMR (CDCl3, 600 MHz) δ 7.00 (1H, s, H-19), 6.64 (1H, bs, H17), 5.45 (1H, ddd, J=15.2, 6.5, 6.5 Hz, H-12), 5.42 (1H, dd, J=6.4, 3.7 Hz, H-15), 5.35 (1H, dt, J=15.2, 7.1 Hz, H-13), 4.42 (1H, m, H-3), 3.58 (1H, ddd, J=8.1, 7.9, 2.8 Hz, H-7), 3.24 (1H, m, H-6), 3.14 (1H, dq, J=4.0, 6.9 Hz, H-6), 2.92 (1H, d, J=7.9 Hz, 7-OH), 2.71 (3H, s, H-21), 2.71 (2H, m, H-2), 2.53 (2H, m, H-14), 2.17 (1H, d, J=2.17 Hz, 3-OH), 2.11 (1H, m, H-11a), 2.06 (3H, bs, H-27), 1.93 (1H, m, H-1 lb), 1.68 (1H, m, H-9a), 1.65 (1H, m, H-10a ), 1.33 (1H, m, H-8), 1.26 (3H, d, J=6.8 Hz, H-24), 1.16 (1H, m, H-10b), 1.12(3K d, J=6.9 Hz, H-22), 1.07 (1H, m, H-9b), 1.00 (3H, d, J=6.8 Hz, H-25); 13C NMR, see Table 1; EIMS m/z 463 [M]+ (6), 290 (21), 289 (20), 204 (23), 194 (19), 190 (22), 168 (100), 164 (48), 157 (14), 152 (19), 151 (17), 139 (15), 111 (18); HREIMS m/z 463.2371 (calcd. for C25H37NO5S, 463.2392).

[0028] trans-Epothilone C2 (29): colorless amorphous solid; [α]22D -3 (c 1.5, MeOH); UV (MeOH) λmax nm (ε) 211 (15800), 248 (11900); IR (KBr) νmax3435, 2963, 2931, 2878, 1731, 1706, 1457,1273, 979 cm−1; 1H NMR (CDCl3, 600 MHz) δ 6.99 (1H, s, H-19), 6.57 (1H, bs, H 17), 5.56*(] H, ddd, J=15.1, 7.4, 7.0 Hz, H-12), 5.41 (1H, ddd, J=15.1, 7.0, 6.9 Hz, H-13), 5.41 (1H, dd, J=7.7, 2.8 Hz, H-15), 4.13 (1H, dddd, J=6.7, 6.2, 5.6, 5.1 Hz, H-3), 3.78 (1H, ddd, J=8.2, 6.5, 1.9 Hz, H-7), 3.18 (1H, d, J=5.6 Hz, 3-OH), 3.06 (1H, dq, J=8.2, 7.1 Hz, H-6), 2.98 (1H, dq, J=6.2, 7.0 Hz, H-4), 2.71 (3H, s, H-21), 2.64 (1H, dd, J=15.1, 6.7 Hz, H2a), 2.54 (1H, dd, J=15.1, 5.1 Hz, H-2b), 2.44 (2H, m, H-14), 2.22 (1H, dddd, J=13.8, 7.0, 6.2, 2.9 Hz, H-11a), 2.10 (3H, d, J=1.1 Hz, H-27), 2.09 (H, d, J=6.5 Hz, 7-OH), 1.88 (1H, dddd, J=13.8, 10.9, 7.4, 2.9 Hz, H-1 lb), 1.65 (1H, m, H-8), 1.63 (1H, m, H-10a ), 1.56 (1H, dddd, J=12.7, 12.7, 3.9, 3.9 Hz, H-9a), 1.20 (3H, d, J=7.1 Hz, H-24), 1.15 (3H, d, J=7.0 Hz, H-23), 1.13 (1H, m, H-10b), 1.04 (1H, m, H-9.b), 1.01 (3H, d, J=7.0.Hz, H-25);13C NMR, see Table 1; EIMS m/z 463 [M]+ (13), 290 (11), 190 (10), 168 (100), 164 (20), 157 (26), 139 (17); HREIMS m/z 463.2383 (calcd. for C25H37NO5S, 463.2392).

[0029] Epothilone I1, (30): colorless amorphous solid; [α]22D -XXX (c XXX, MeOH); UV (MeOH) λmax f nm (ε) XXX; IR(KBr) νmaxXXX cm−1; 1H NMR (CDCl3, 300 MHz) 6.96 (1H, s, H-1 9), 6.54 (1H, bs, H-1 7), 5.49 (Iii, ddd, J=10.3, 7.3, 7.3 Hz, H-12), 5.33 (1H, dd, J=8.3, 4.4 Hz, H-15), 5.31 (1H, m, H-133), 4.15 (1H, ddd, J=8.0, 5.0, 4.6 Hz, H-3), 3.80 (1H, m, H-7), 3.21 (1H, dq, J=6.0, 6.9 Hz, H-6), 2.89 (1H, d, J=5.0 Hz, 3-OH); 2.70 (3H, s, H-21), 2.65 (1H, ddd, J=15.8, 8.5, 8.3 Hz, H-14a), 2.42 (2H, m, H-2), 2.35 (1H, m, H-14b), 2.27 (1H, bd, 0.1=3.3 Hz, 7-OH), 2.13 (1H, m, H-11a), 2.09 (3H, d, J=1.2 Hz, H-27), 2.00 (1H, m, H-1 lb), 1.72 (1H, m, H-8), 1.40 (2H, m, H-10p), 1.37 (1H, m, H-9pa), 1.36 (2H, m, H-9a), 1.32 (3H, s, .H-23), 1.27 (3H, m, H-9b and H-10a), 1.13 (3H, d, J=6.9 Hz, H-24), 1.09 (3H, s, H-22), 0.94 (3H, d, J=6.9 Hz, H-25); 13C NMR (CDCl3, 75 MHz) δ 221.3 (s, C-5), 171.1 (s, C-1), 164.8 (s, C-20), 152.4 (s, C-18), 137.4 (s, C-16), 133.8 (d, C-12), 124.6 (d; C-13), 120.0 (d, C-17), 116.2 (d, C-19), 78.8 (d, C-15), 74.9 (d, C-7), 74.7 (d, C-3), 51.6 (s, C-4), 43.7 (d, C-6), 38.9 (t, C-2), 34.3 (d, C-8), 31.6 (t, C-14), 29.3 (t, C-9a, 28.6 (t, C-10β), 28.2 (t, C-10a), 26.6 (t, C-11), 24.8 (t, C-9β), 23.6 (q, C-22), 19.3 (q, C23), 19.3 (q, C-21), 16.5 (q, C-25), 15.5 (q, C:27), 13.7 (q, C-24); EIMS m/z 505 [M]+ XXX; HREIMS m/z 505.XXX (calcd. for C28H43NO5S, 505.XXX).

[0030] Epothilone I2, (31): colorless amorphous solid; [α]22D -XXX (c XXX, MeOH); UV (MeOH) λmax nm (ε) XXX; IR (KBr) νmax XXX cm−1; 1H NMR (CDCl3, 300 MHz) α 6.95 (1H, s, H-19), 6.53 (1H, bs, H-17), 5.40 (1H, m, H-12), 5.38 (1H, dd, J=9.8, 3.3 Hz, H-15), 5.37 (1H, m, H-133).4.21 (1H, ddd, 0.1=8.6, 3.8, 3.6 Hz, H-3), 3.85 (1H, ddd, J=8.5, 5.8, 2.2 Hz, H7), 3.18 (1H, dq, J=8.5, 7.0 Hz, H-6), 2.70 (3H, s, H-21), 2.65 (1H, ddd, J=15.2, 9.8, 9.0 Hz, H-14a), 2.51 (1H, d, J=3.6 Hz, 3-OH), 2.37 (2H, m, H-2), 2.32 (1H, bd, J=15.2 Hz, H-14b), 2.09 (3H, d, J=1.3 Hz, H-27), 2.07 (2H, m, H-11), 1.78 (1H, m, H-8), 1.65 (1H, d, J=5.8 Hz, 7-OH), 1.57 (1H, m, H-10βa), 1.44 (1H, m, H-10αa), 1.42 (1H, m, H-9β, 1.32 (3H, s, H-23), 1.21 (1H, m, H-10βb), 1.17 (3H, d, J=7.0 Hz, H-24), 1.13 (2H, m, H-9α),1.06 (3H, s, H-22), 0.95 (3H, d, J=7.0 Hz, H-25α), 0.91 (3H, d, J=6.5 Hz, H-25β), 0.68 (1H, m, H-10.b); 13C NMR (CDCl3, 100 MHz) δ 220.4 (s, C-5), 171.3) (s, C-1), XXX (s, C-20), 152.4 (s, C-18), 137.6 (s, C-16), 13)4.5 (d, C-12), 125.3) (d, C-13), 119.6 (d, C-17), 116.2 (d, C-19), 78.6 (d, C-15), 77.2 (d, C-7), 75.0 (d, C-3), 51.0 (s, C-4), 44.6 (d, C-6), 38.2 (t, C-2), 36.9 (t, C-9α), 34.5 (t, C-10α), 32.6 (d, C-8), 32.0 (t, C-14), 30.0 (d, C-9β), 27.4 (t, C-11), 26.6 (t, C-10p), 25.0 (q, C-22), 21.5 (q, C-25β), 19.3 (q, C-21), 17.9 (q, C-25α), 17.7 (q, C-23), 15.8 (q, C-24), 15.6 (q, C-27); EIMS m/z 519 MV XXX; HREIMS ,n/. 519.XXX (calcd. for C29H45NO5S, 519.XXX).

[0031] Epothilone I3 (32): colorless amorphous solid; [α]22D -XXX (c XXX, MeOH); UV (MeOH) λmax nm (ε) XXX; IR (KBr) νmax XXX cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.95 (1H, s, H-19), 6.52 (1H, bs, H-17), 5.32 (1H, dd, J=9.1, 3.0 Hz, H-15), 5.08 (1H, dd, J=8.˜, 3.9 Hz, H-13), 4.13 (1H, ddd, J=9.4,4.3, 3.2 Hz, H-3), 3.81 (1H, m, H-7), 3.18 (1H, dq, J=6.8, 7.0 Hz, H-6), 2.83 (1H, d, J=4.3 Hz, 3-OH), 2.70 (3H, s, H-21), 2.61 (1H, ddd, J=15.8,9.1, 8.5 Hz, H-14 a), 2.43 (1H, dd, J=14.0, 3.2 Hz, H-2a), 2.3 8 (2H, dd, J=14.0, 9.4 Hz, H-2b), 2.30 (1H, bd, J=15.8 Hz, H-14b), 2.16 (1H, ddd, J=14.1, 8.3, 7.4 Hz, H-11a), 2.08 (3H, d, J=1.0 Hz, H-27), 1.99 (1H, d, J=4.7 Hz, 7-OH), 1.92 (1H, ddd, J=14.1, 6.3, 6.3 Hz, H-1 Ib), 1.82 (1H, m, H-8), 1.67 (3H, s, H-26), 1.51 (1H, m, H-10pa), 1.40 (1H, m, H-9β), 1.33 (1H, m, H-10βb), 1.31 (3H, s, H-23), 1.27 (1H, M H-10αa), 1.23 (1H, m, H-9αa), 1.16 (3H, d, J=7.0 Hz, H-24), 1.10 (1H, m, H-9αb), 1.07 (3H, s, H-22), 0.95 (3H, d, J=7.0 Hz, H-25α), 0.92 (3H, d, J=6.5 Hz, H-25β), 0.75 (1H, m, H-10αb); EIMS m/z 533 M+XXX; HREIMS m/z 533.XXX (calcd. for C30H47NO5S, 533.XXX).

[0032] Epothilone 14 (33): colorless amorphous solid; [α]22D -XXX (c XXX, MeOH); UV (MeOH) λmax nm (ε) XXX; IR (KBr) νmax XXX cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.95 (1H, s, H-19), 6.53 (1H, bs, H-17), 5.47 (1H, dt, J=11.1, 5.8 Hz, H-12), 5.33 (1H, ddd, J=9.2, 3.9, 0.5 Hz, H-15), 5.33 (1H, m, H-13), 4.09 (1H, dddd, J=9.6, 8.1, 4.5, 3.3 Hz, H-3), 3.83 (1H, m, H-7), 3.57 (1H, bs, 3-OH), 2.89 (1H, dq, J=7.4, 7.1 Hz, H-6), 2.83 (1H, dq, J=8.1, 7.1 Hz, H-4), 2.70 (3H, s, H-21), 2.64 (1H, m, H-14a), 2.42 (1H, dd, J=14.2, 3.3 Hz, H-2a), 2.43 (1H, dd, J=14.2, 9.6 Hz, H-2b), 2.30 (1H, m, H-14b), 2.10 (3H, d, J=1.3 Hz, H-27), 2.09 (2H, m, H-11), 1.81 (1H, m, H-8), 1.74 (1H, bd, J=5.6 Hz, 7-OH), 1.53 (1H, m, H-10βa), 1.49 (1H, m, H-9β), 1.47 (1H, m, H-10αa), 1.27 (1H, m, H-10βb), 1.24 (1H, m, H-9αa) 1.17 (3H, d, J=7.1 Hz, H-23), 1.14 (1H, m, H-9αb) 1.08 (3H, d, J=7.1 Hz, H-24), 0.97 (3H, d, J=6.9 Hz,H-25α), 0.91 (3H, d, J=6.5 Hz, H-25β), 0.79 (1H, m, H-10αb); 13C NMR (CDCl3, 100 MHz) δ 217.0 (s, C-5), 170.8 (s, C-1), 164.8 (s, C-20), 152.4 (s, C-18), 137.1 (s, C-16), 134.6 (d, C-12), 124.7 (d, C-13), 120.2 (d, C-17), 116.4 (d, C-19), 78.7 (d, C-15), 76.4 (d, C-7), 71.3 (d, C-3), 50.7 (d, C4), 50.1 (d, C-6), 40.7 (t, C-2), 38.5 (t, C-9α), 35.5 (t, C-10α), 33.4 (d, C-8), 31.8 (t, C-14), 30.0 (d, C-9β), 27.2 (t, C-11), 26.7 (t, C-10β), 21.4 (q, C-25βp), 19.3 (q, C-21), 18.2 (q, C-25α), 15.4 (q, C-27), 14.4 (q, C-24), 13.1 (q, C-23); EIMS m/z 505 [M]+ XXX; HREIMS m/z 505.XXX (calcd. for C28H43NO5S, 505.XX.X).

[0033] Epothilone 15, (34): colorless amorphous solid; [α]22D -XXX (c XXX, MeOH); UV (MeOH) λmax nm (ε) XXX; IR (KBr) νmax XXX cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.97 (1H, s, H-19), 6.52 (1H, bs, H-17), 5.32 (1H, dd, J=7.1, 6.2 Hz, H-15), 5.03 (1H, dd, J=8.4, 5.0 Hz, H-13), 4.05 (1H, dddd, J=7.5, 7.2, 5.9, 4.6 Hz, H-3), 3.91 (1H, m, H-7), 3.17 (1H, d, J=5.9 Hz, 3-OH), 2.94 (1H, d q, J=7.2, 7.1 Hz, H-4), 2.87 (1H, dq, J=6.5, 6.9 Hz, H-6), 2.70 (3H, s, H-21), 2.62 (1H, dd, J=14.6, 4.6 Hz, H-2a), 2.60 (1H, M, H-14a), 2.53 (1H, dd, J=14.6, 7.5 Hz, H-2b), 2.31 (1H, m, H-14b), 2.10 (3H, d, J=1.1 Hz, H-27), 2.10 (1H, M, H-11a), 2.02 (1H, m, H-I I b), 1.97 (1H, bd, 1=5.6 Hz, 7-OH), 1.84 (1H, m, H-8), 1.66 (3H, s, H-26), 1.55 (1H, m, H-9p) 1.49 (1H, m, H-100a), 1.39 (1H, m, H-100b), 1.33. (1H, m, H-10αa), 1.31 (1H, m, H-9α), 1.15 (3H, d, J=7.1 Hz, H-23), 1.12 (1H, m, H-9αb), 1.11 (3H d, J=6.9 Hz, H-24), 0.97 (3H, d, J=6.9 Hz,H-25α), 0.94 (1H, m, H-10αb), 0.93 (3H, d, J=6.6 Hz, H-25p); EIMS m/z 519 μl+XXX; HREIMS ink 519.XXX (calcd. for C29H45NO5S,519.XXX).

[0034] Epothilone I6 (35): colorless amorphous solid; [C]22D -XXX (c XXX, MeOH); UV (MeOH) λmax nm (ε) XXX; IR (KBr) νmax XXX cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.97 (1H, s, H-19), 6.52 (1H, bs, H-1 7), 5.24 (1H, dd, J=6.9, 6.9 Hz, H-15), 5.02 (1H, dd, J=8.8, 5.2 Hz, H-13), 4.22 (1H, tdd, J=6.1, 5.6, 4.8 Hz, H-3), 3.76 (1H, ddd, J=6.1, 5.7, 5.6 Hz, H-7), 3.13 (1H, d, J=5.6 Hz, 3-OH), 3.05 (1H, dq, J=4.8, 7.0 Hz, H-4), 2.79 (1H, dq, J=5.6, 6.9 Hz, H-6), 2.70 (3H, s, H-21), 2.62 (1H, m, H-14a), 2.57 (2H, d, J=6.1 Hz, H-2a), 2.30 (1H, m, H-14b), 2.08 (3H, d, J=1.0 Hz, H-27), 2.02 (2H, m, H-11), 1.73 (1H, d, J=6.1 Hz, 7-OH), 1.69 (1H, m, H-8), 1.66 (3H, s, H-26), XXX (H-9α, H-9β, H-10α, H-10β), 1.21 (3H, d, J=7.0. Hz, H-22), 1.16 (3H, d, J=6.9 Hz, H-24), 0.94 (3H, d, J=6.9 Hz,H-25α), 0.91 (3H, d, J=6.4 Hz, H-25β); EIMS m/z 519 [M]+ XXX; HREIMS m/z 519.XXX (calcd. for C29H45NO5S, 519.XXX).

[0035] Epothilone K (36): colorless amorphous solid; [α]22D -7 (c 0.08, MeOH); UV (MeOH) λmax nm (ε) 212 (16700), 248 (12500); IR (KBr) νmax3431, 2963, 2927, 2856, 1731, 1712, 1262, 1093, 1021, 802 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.95 (1H, s, H-19), 6.51 (1H, bs, H-17), 5.49 (3H, m, H-15, H-13, and H-12), 4.04 (1H, dddd, J=7.9, 7.6, 6.9, 3.3 Hz, H-3), 3.36 (1H, dq, J=6.9, 6.8 Hz, H-6), 2.83 (1H, d, J=7.6 Hz, 3-OH), 2.75 (1H, ddd, J=16.1, 6.6, 3.4 Hz, H-14a), 2.74 (1H, dd, J=15.3, 3.3 Hz, H-2a), 2.71 (3H, s, H-21), 2.58 (2H, m, H-14b and H-8), 2.50 (1H, dd, J=15.3, 7.9 Hz, H-2b), 2.29 (1H, m, H-11a), 2.10 (1H, m, H-1 lb), 2.09 (311, d, J=0.7 Hz, H-27), 1.78 (1H,-m, H-9a), 1.65 (1H, m, H-10a ), 1.48 (1H, m, H-10b), 1.18 (1H, m, H-9b), 1.15 (3H, d, J=6.8 Hz, H-22), 1.03 (3H, d, J=6.5 Hz, H-25); EIMS m/z 405 [M]+ (38), 317 (12), 260 (9), 232 (10), 204 (14), 190 (16), 168 (100), 164 (30), 151 (28); HREIMS m/z 405.″X (calcd. for C26H39NO5S, 405.XXX).

[0036] (37): colorless amorphous solid; [α]22D -27.5 (c 0.4, MeOH); UV (MeOH) λmax nm (ε) 211 (16100), 247 (12100); IR (KBr) νmax 3431, 2967, 2929, 2875, 1704, 1462, 1381, 1010 cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.94 (1H, s, H-19), 6.55 (1H, bs, H-17), 5.56 (1H, dtt, J=10.8, 7.3, 1.4 Hz, H-12), 5.39 (1H, dtt, J=10.8, 7.3, 1.4 Hz, H-13), 4.17 (1H, t, J=6.6 Hz, H-15), 3.50 (1H, ddd, J=8.7,2.6,2.6 Hz, H-7), 3.10 (1H, d, J=2,6,7-OH), 2.90 (1H, dq, J=2.6, 7.2 Hz, H-6), 2.77 (1H, sep, J=6.9 Hz, H-4), 2.70 (3H, s, H-21), 2.40 (2H, m, H-14), 2.07 (2H, m, H-11), 2.04 (3H, d, J=1.1 Hz, H-27), 1.78 (1H, bs, 15-OH), 1.74 (1H, m, H-9a),.1.50 (1H, m, H-8), 1.46 (1H, m, H-10a ), 1.27 (1H, m, H-10b), 1.11 (1H, m, H-9b), 1.094 (3H, d, J=6.9 Hz, H-23), 1.089 (3H, d, J=6.9 Hz, H-22), 1.08 (3H, d, J=7.2 Hz, H-24), 0.82 (3H, d, J=6.7 Hz, H-25); 13C NMR (CDCl3, 100 MHz) δ 220.5 (s, C-5), 164.6 (s, C-20), 152.9 (s, C-18), 141.5 (s, C-16), 133.4 (d, C-12), 125.0 (d, C-13), 119.2 (d, C-17), 115.6 (d, C-19), 77.2 (d, C-15), 74.9 (d, C-7), 44.9 (d, C-6), 40.0 (d, C-4), 35.5 (d, C-8), 33.5 (t, C-14), 32.3 (t, C-9), 27.9 (t, C-11), 26.9 (t, C-10), 19.2 (q, C-21), 18.6 (q, C-23), 18.1 (q, C-22), 15.6 (q, C-25), 14.4 (q, C-27), 9-3 (q, C-24); EIMS m/z 407 [M]+ (0.1), 204 (0.8), 168 (100), 140 (3.4); HREIMS m/z 407.XXX (calcd. for C23H37NO3S, 407.XXX).

[0037] (38): colorless amorphous solid; [α]22D+25.0 (c 0.5, MeOH); UV (MeOH) λmax nm (ε) 212 (17700), 247 (13400); IR (KBr) νmax 3427, 2971, 2933, 2878, 2858, 1709, 1457, 1377, 1186,1023 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.95 (1H, s, H-19), 6.55 (1H, bs, H-17), 5.52 (1H, dtt, J=10.9, 7.2, 1.4 Hz, H-12), 5.39 (1H, dtt, J=10.9, 7.1, 1.2 Hz, H-13), 4.18 (1H, ddt, J=3.4, 0.4, 6.7 Hz, H-1 5), 2.71 (3H, s, H-21), 2.51 (1H, bq, J=6.8 Hz, H-8), 2.48 (1H, dq, J=17.7, 7.4 Hz, H-6a), 2.41 (1H, dq, 1=17.7, 7.2 Hz, H-6b), 2.39 (2H, ddd, J=7.1, 6.7, 1.4 Hz, H-14), 2.06 (2H, ddt, 7.2, 1.2, 7.0 Hz, H-11), 2.05 (3H, d, J=1.4 Hz, H-27), 1.81 (1H, d, J=3.4 Hz, 15-01-1), 1.66 (1H, m, H-9a), 1.32 (1H, m, H-9b), 1.31 (2H, m, H-10), 1.06 (3K d, J=6JHz, H-25), 1.04 (3H, dd, J=7.4, 7.2 Hz, H-24); 13C NMR (CDCl3, 75 MHz) δ 215.3 (s, C-7), 164.6 (s, C-20), 152.9 (s, C-18), 141.5 (s, C-16), 132.7 (d, C-12), 125.3 (d, C-13), 119.2 (d, C-17), 115.6 (d, C-19), 77.2 (d, C-15), 46.0 (d, C-8), 34.3 (t, C-14), 33.5 (t, C-6), 32.7 (t, C-9), 27.5 (t, C-11), 27.3 (t, C-10), 19.2 (q, C-21), 16.5 (q, C-25), 14.4 (q, C-27), 7.8 (q, C-24); EIMS m/z 335 [M]+ (2), 317 (4), 170 (27), 169 (67), 168 (100), 140 (20); HREIMS m/z 335.1912 (calcd. for C19H29NO2S, 335.1919).

[0038] (39): colorless amorphous solid; [α]22D+26.4 (c 0.27, MeOH); UV (MeOH) λmax nm (ε) 203 (19100), 244 (12500); IR (KBr) νmax3430, 2970, 2934, 2877, 1710, 1458, 1377, 1184 cm−1; 1H NMR (CDCl3, 400 MHz) δ 6.94 (1H, s, H-19), 6.55 (1H, bs, H-17), 5.17 (1H, t, J=7.3 Hz, H-13), 4.13 (1H, m, H-15), 2.70 (3H, s, H-21), 2.51 (1H, bq, J=6.8 Hz, H-8), 2.47 (1H, dq, J=17.7, 7.2 Hz, H-6a), 2.41 (1H, dq, J=17.7, 7.2 Hz, H-6b), 2.33 (2H, bdd, J=7.3, 6.8 Hz, H-14), 2.05 (3H, d, J=1.2 Hz, H-27), 2.03 (2H, m, H-11), 1.71 (1H, d, J=3.2 Hz, 15-OH), 1.69 (3H, d, J=1.3 Hz, H-26), 1.62 (1H, m, H-9a), 1.32 (3H, m, H-10 and H-9b), 1.06 (3H, d, J=6.9 Hz, H-25), 1.03 (3H, t, J=7.2 Hz, H-24); EIMS m/z 349 [M]+ (0.7), 331 (1.7), 168 (100), 140 (5.1); HREIMS m/., 349.XXX (calcd. for C20H31NO2S, 349.XXX).
1TABLE 1Activity of epothilones and compounds (1) to (39) against mousefibroblasts (L929, IC 50/ng/ml)EpothiloneStructural typeAγBγCγDγtrans CγStarting(1) 4(2) 1-2(14) 50-100(15) 20—epothilone21-Hydroxy(3) 10(4) 1.5———(E&F)Oxozoles(10) 6(11) 1(12) 120(13) 11—(G&H)(R)-4-(5) 20—(16) 200(17) 20(28) 400Desmethyl (X1)(S)-4-(6) 7—(10) 25-30(19) 12(29) 80Desmethyl (X2)6-Desmethyl——(20 1500——(X3)8-Desmethyl——(21) 800——(X4)8,9-Dehydro——(22) 1500(23) 200(X5)10,11-Dehydro——(24) 120——(X6)14-Hydroxy——(25)——(X7)16-Desmethyl(7) 20—(26) 250(X8)27-Hydroxy(8) 100—(27) 200——(X9)21-Methyl—(9) 1.5———(X10)Compound——(36) 180Compound——(37) 50——Compound——(38) 2000(39) 500—

Claims
  • 1. Epothilone of formula
  • 2. Epothilone of formula
  • 3. Epothilone of formula
  • 4. Epothilone of formula
  • 5. Epothilone of formula
  • 6. Epothilone of formula
  • 7. Epothilone of formula
  • 8. Epothilone of formula
  • 9. Epothilone of formula
  • 10. Epothilone of formula
  • 11. Epothilone of formula
  • 12. Compound of formula
  • 13. Compound of formula
Priority Claims (1)
Number Date Country Kind
19826988.9 Jun 1998 DE
Parent Case Info

[0001] This application is a division of U.S. application Ser. No. 09/719,932, filed Mar. 21, 2001, allowed, which is the U.S. National Stage of PCT/EP99/04244, filed Jun. 18, 1999, which claims priority to DE 19826988.9, filed Jun. 18, 1998, the disclosure of each of which is incorporated by reference herein in its entirety.

Divisions (1)
Number Date Country
Parent 09719932 Mar 2001 US
Child 10457098 Jun 2003 US