Biomimetic Cyclization of Indole Terpene Precursors
2221
1.26 (3H, s), 1.30 (3H, s), 1.62 (3H, br s), 1.62–1.65 (2H, complex),
1.67 (3H, br s), 1.97–2.10 (2H, complex), 2.10–2.19 (4H, complex),
2.70 (1H, t, J ¼ 6:2 Hz), 4.15 (2H, t, J ¼ 6:3 Hz), 5.16 (1H, t,
J ¼ 6:3 Hz), 5.41 (1H, t, J ¼ 6:8 Hz). NMR ꢀC (CDCl3, 100 MHz):
15.9 (CH3), 16.2 (CH3), 18.7 (CH3), 24.8 (CH3), 26.1 (CH2), 27.3
(CH2), 36.3 (CH2), 39.4 (CH2), 58.3 (C), 59.3 (CH2), 64.1 (CH), 123.6
(CH), 124.5 (CH), 134.3 (C), 139.4 (C). MS m=z: 220 ([M-H2O]þ, 5),
199 (25), 189 (10), 177 (9), 159 (25), 153 (26), 143 (33), 135 (71), 121
(56), 109 (75), 93 (84), 85 (86), 81 (100), 69 (69), 59 (59). HRMS m=z:
calcd. for C15H24O ½M ꢁ H2Oꢃþ, 220.1827; found, 220.1864.
4 ꢂ ArH). NMR ꢀC (CDCl3, 100 MHz): 15.9 (CH3), 16.0 (CH3),
16.4 (CH3), 19.2 (C), 25.7 (CH3), 26.4 (CH2), 26.6 (CH2), 26.7 (CH3),
26.9 (3 ꢂ CH3), 32.2 (CH2), 38.2 (CH2), 39.5 (CH2), 39.6 (CH2), 61.2
(CH2), 71.1 (CH), 72.5 (C), 124.0 (CH), 124.2 (C), 126.0 (CH), 127.6
(4 ꢂ CH), 129.5 (2 ꢂ CH), 133.0 (C), 134.1 (2 ꢂ C), 135.0 (C), 135.6
(4 ꢂ CH), 137.1 (C). MS m=z: 488 (½M ꢁ t-Bu ꢁ Brꢃþ, 2), 289 (4), 71
(7), 229 (4), 199 (100), 161 (10), 149 (17), 135 (50), 121 (25), 81 (91),
71 (27), 69 (23). HRMS m=z: calcd. for C32H44O2Si ½M ꢁ t-Bu ꢁ
Brꢃþ, 488.3105; found, 488.3095.
(2E,6E,10E)-tert-Butyldiphenylsiloxy-14,15-epoxy-3,7,11,15-tetra-
methylhexadeca-2,6,10-triene (14). Bromohydrine 13 (1.37 g, 2.19
mmol) was converted to 14 (943 mg, 80%) as a colorless oil according
to the method of Ceruti et al.21) IR ꢁmax (film) cmꢁ1: 2959, 2930, 2857,
1472, 1461, 1428, 1378, 1111, 1057, 823, 738, 701, 612. NMR ꢀH
(CDCl3, 400 MHz): 1.04 (9H, s), 1.25 (3H, s), 1.29 (3H, s), 1.44 (3H,
br s), 1.60 (3H, br s), 1.61 (br s), 1.60–1.69 (2H, complex), 1.94–2.20
(10H, complex), 2.69 (1H, t, J ¼ 6:3), 4.22 (2H, d, J ¼ 6:1 Hz), 5.12
(1H, t, J ¼ 6:9 Hz), 5.16 (1H, t, J ¼ 6:6 Hz), 5.38 (1H, t, J ¼ 6:1 Hz),
7.34–7.45 (6H, 6 ꢂ ArH), 7.66–7.72 (4H, 4 ꢂ ArH). NMR ꢀC (CDCl3,
100 MHz): 16.0 (CH3), 16.1 (CH3), 16.4 (CH3), 18.8 (CH3), 24.9
(CH3), 26.4 (CH2), 26.9 (3 ꢂ CH3), 27.5 (CH2), 36.3 (CH2), 39.5
(CH2), 39.7 (CH2), 58.2 (C), 61.2 (CH2), 64.2 (CH), 124.1 (CH), 124.2
(CH), 124.9 (CH), 127.5 (4 ꢂ CH), 129.5 (2 ꢂ CH), 133.6 (CH), 134.1
(2 ꢂ C), 134.2 (C), 135.1 (C), 135.6 (4 ꢂ CH),137.0 (C). MS m=z: 487
(½M ꢁ t-Buꢃþ, 9), 351 (3), 271 (13), 199 (100), 181 (12), 164 (14), 135
(65), 121 (34), 93 (53), 77 (35), 69 (31). HRMS m=z: calcd. for
(2E,6E)-Bromo-10,11-epoxy-3,7,11-trimethyldodeca-2,6-diene (35).
Compound 34 (1.14 g, 4.03 mmol) was converted to crude 35 (1.23 g)
as a colorless oil by the same method as that used for the synthesis of
10. IR ꢁmax (film) cmꢁ1: 3458, 2960, 2924, 2853, 2363, 2339, 1654,
1447, 1377, 1202, 1119, 874, 857. NMR ꢀH (CDCl3, 400 MHz): 1.25
(3H, s), 1.29 (3H, s), 1.61 (3H, br s), 1.58–1.65 (2H, complex), 1.72
(3H, br s), 2.05–2.15 (6H, complex), 2.69 (1H, t, J ¼ 7:2 Hz), 4.08
(2H, d, J ¼ 7:4 Hz), 5.13 (1H, t, J ¼ 6:7 Hz), 5.52 (1H, t, J ¼ 7:4 Hz).
NMR ꢀC (CDCl3, 100 MHz): 15.9 (CH3), 16.0 (CH3), 18.7 (CH3), 24.9
(CH3), 26.1 (CH2), 27.5 (CH2), 29.6 (CH2), 36.3 (CH2), 39.4 (CH2),
58.3 (C), 64.1 (CH), 120.7 (CH), 124.0 (CH), 134.8 (C), 143.4 (C). MS
m=z: 221 (½M ꢁ Brꢃþ, 5), 203 (7), 18 (2), 153 (19), 107 (43), 101 (91),
93 (78), 85 (77), 81 (85), 71 (83), 59 (100). HRMS m=z: calcd. for
C15H25O ½M ꢁ Brꢃþ, 221.1900; found, 221.1884.
3-(10,11-Epoxyfarnesyl)indole (2). Crude 35 (1.23 g) was converted
to 2 (677 mg, 50%, 3 steps) as a colorless oil by the same method as
that used for the synthesis of 11. IR ꢁmax (film) cmꢁ1: 3417, 3346,
3055, 2961, 2923, 2852, 1455, 1378, 1351, 1338, 1249, 1225, 1122,
1092, 1045, 1009, 868, 800, 740. NMR ꢀH (CDCl3, 400 MHz): 1.24
(3H, s), 1.29 (3H, s), 1.58–1.63 (2H, complex), 1.62 (3H, br s), 1.75
(3H, br s), 2.05–2.20 (6H, complex), 2.70 (1H, t, J ¼ 6:2 Hz), 3.46
(2H, d, J ¼ 7:2 Hz), 5.18 (1H, t, J ¼ 6:1 Hz), 5.46 (1H, t, J ¼ 7:2 Hz),
6.93 (1H, d, J ¼ 2:2 Hz), 7.09 (1H, t, J ¼ 7:8 Hz), 7.17 (1H, t,
J ¼ 7:8 Hz), 7.34 (1H, t, J ¼ 7:8 Hz), 7.58 (1H, t, J ¼ 7:8 Hz), 8.03
(1H, br s). NMR ꢀC (CDCl3, 100 MHz): 15.9 (CH3), 16.1 (CH3), 18.7
(CH3), 23.9 (CH2), 24.9 (CH3), 26.4 (CH2), 27.5 (CH2), 36.3 (CH2),
39.6 (CH2), 58.5 (C), 64.3 (CH), 111.1 (CH), 116.1 (C), 119.0 (CH),
119.1 (CH), 121.3 (CH), 121.9 (CH), 123.2 (CH), 124.8 (CH), 127.5
(C), 134.1 (C), 135.4 (C), 136.6 (C). MS m=z: 337 (Mþ, 96), 320 (7),
238 (14), 210 (9), 196 (32), 184 (100), 170 (70), 168 (63), 143 (21),
130 (74), 117 (36), 93 (7), 85 (11), 59 (10). HRMS m=z: calcd. for
C
32H43O2Si ½M ꢁ t-Buꢃþ, 487.3032; found, 487.3025.
(2E,6E,10E)-14,15-Epoxy-3,7,11,15-tetramethylhexadeca-2,6,10-
trien-1-ol (36). Compound 14 (943 mg, 1.73 mmol) was converted to
36 (408 mg, 77%) as a colorless oil by the same method as that used for
the synthesis of 9. IR ꢁmax (film) cmꢁ1: 3419, 2961, 2923, 2855, 1733,
1668, 1598, 1446, 1379, 1322, 1249, 1121, 1004, 871, 768, 681. NMR
ꢀH (CDCl3, 400 MHz): 1.26 (3H, s), 1.30 (3H, s), 1.60 (3H, br s), 1.62
(3H, br s), 1.68 (3H, br s), 1.57–1.69 (2H, complex), 1.97–2.20 (10H,
complex), 2.70 (1H, t, J ¼ 6:4), 4.15 (2H, d, J ¼ 7:0 Hz), 5.12 (1H, t,
J ¼ 7:2 Hz), 5.16 (1H, t, J ¼ 6:8 Hz), 5.41 (1H, t, J ¼ 7:0 Hz). NMR
ꢀC (CDCl3, 100 MHz): 16.0 (2 ꢂ CH3), 16.1 (CH3), 16.3 (CH3), 18.7
(CH3), 24.8 (CH3), 26.3 (CH2), 26.6 (CH2), 27.5 (CH2), 36.3 (CH2),
39.5 (CH2), 39.6 (CH2), 58.3 (C), 59.4 (CH2), 64.2 (CH), 123.5 (CH),
123.9 (CH), 124.8 (CH), 134.0 (C), 135.2 (C), 139.6 (C). MS m=z: 288
(½M ꢁ H2Oꢃþ, 4), 202 (4), 189 (4), 161 (12), 153 (15), 135 (46), 119
C
23H31NO (Mþ), 337.2406; found, 337.2388.
(34), 93 (79), 81 (100), 59 (17). HRMS m=z: calcd. for C20H32
½M ꢁ H2Oꢃþ, 288.2453; found, 288.2446.
O
(2E,6E,10E,14E)-tert-Butyldiphenylsiloxy-3,7,11,15-tetramethylhexa-
deca-2,6,10-tetraene (12). Geranylgeraniol (2.52 g, 8.67 mmol) was
converted to silyl ether 12 (4.08 g, 89%) as a colorless oil by the same
method as that used for the synthesis of 7. IR ꢁmax (film) cmꢁ1: 2960,
2929, 2856, 1446, 1428, 1111, 1057, 823, 737, 700, 688, 613, 504, 490.
NMR ꢀH (CDCl3, 400 MHz): 1.04 (9H, s), 1.44 (3H, br s), 1.59 (3H, br
s), 1.90 (6H, complex), 1.67 (3H, br s), 1.95–2.10 (12H, complex),
4.22 (2H, d, J ¼ 6:3 Hz), 5.09 (1H, t, J ¼ 6:9 Hz), 5.11 (1H, t,
J ¼ 6:6 Hz), 5.38 (1H, t, J ¼ 6:3 Hz), 7.34–7.45 (6H, 6 ꢂ ArH), 7.65–
7.70 (4H, 4 ꢂ ArH). NMR ꢀC (CDCl3, 100 MHz): 16.0 (CH3), 16.1
(CH3), 16.4 (CH3), 17.7 (CH3), 19.2 (C), 25.7 (CH3), 26.4 (CH3), 26.7
(CH2), 26.8 (CH2), 26.9 (3 ꢂ CH3), 39.6 (CH2), 39.7 (2 ꢂ CH2), 61.2
(CH2), 124.0 (2 ꢂ CH), 124.3 (CH), 124.4 (CH), 127.6 (4 ꢂ CH),
129.5 (2 ꢂ CH), 131.3 (C), 134.1 (2 ꢂ C), 134.9 (C), 135.2 (C), 135.6
(4 ꢂ CH), 137.1 (C). MS m=z: 471 (½M ꢁ t-Buꢃþ, 8), 433 (5), 272 (6),
199 (100), 181 (11), 135 (36), 93 (30), 81 (39), 69 (96). HRMS m=z:
calcd. for C32H43OSi ½M ꢁ t-Buꢃþ, 471.3032; found, 471.3034.
(2E,6E,10E)-Bromo-14,15-epoxy-3,7,11,15-tetramethylhexadeca-
2,6,10-triene (37). Compound 36 (408 mg, 1.33 mmol) was converted
to crude 37 (497 mg) as a colorless oil by the same method as that used
for the synthesis of 10. IR ꢁmax (film) cmꢁ1: 2960, 2924, 2854, 1777,
1655, 1449, 1377, 1324, 1248, 1200, 1174, 1121, 897, 872, 793, 5843.
NMR ꢀH (CDCl3, 400 MHz): 1.26 (3H, s), 1.29 (3H, s), 1.59 (3H, br s),
1.62 (3H, br s), 1.61–1.69 (2H, complex), 1.78 (3H, br s), 1.96–2.20
(10H, complex), 2.69 (1H, t, J ¼ 6:3), 4.01 (2H, d, J ¼ 8:4 Hz), 5.08
(1H, t, J ¼ 5:8 Hz), 5.16 (1H, t, J ¼ 6:7 Hz), 5.52 (1H, t, J ¼ 8:4 Hz).
NMR ꢀC (CDCl3, 100 MHz): 16.0 (3 ꢂ CH3), 18.7 (CH3), 24.8 (CH3),
26.1 (CH2), 26.6 (CH2), 27.5 (CH2), 29.5 (CH2), 36.3 (CH2), 39.5
(CH2), 39.6 (CH2), 58.3 (C), 64.2 (CH), 120.6 (CH), 123.5 (CH), 124.8
(CH), 134.1 (C), 135.5 (C), 143.5 (C). MS m=z: 289 (½M ꢁ Brꢃþ, 3),
252 (6), 199 (35), 153 (15), 147 (17), 135 (51), 119 (72), 107 (49), 93
(100), 58 (21). HRMS m=z: calcd. for C20H33O ½M ꢁ Brꢃþ, 289.2526;
found, 289.2526.
(2E,6E,10E)-tert-Butyldiphenylsiloxy-14-bromo-15-hydroxyl-3,7,11,15-
tetramethylhexadeca-2,6,10-triene (13). Silyl ether 12 (1.46 g, 2.77
mmol) was converted to bromohydrine 13 (1.37 g, 79%) as a colorless
3-(14,15-Epoxygeranylgeranyl)indole (3). Crude 37 (497 mg) was
converted to 3 (306 mg, 57%) as a colorless oil by the same method as
that used for the synthesis of 10. IR ꢁmax (film) cmꢁ1: 3417, 3343,
3054, 2961, 2920, 2850, 1665, 1618, 1455, 1379, 1351, 1337, 1249,
1224, 1122, 1092, 1009, 867, 739, 423. NMR ꢀH (CDCl3, 400 MHz):
1.26 (3H, s), 1.30 (3H, s), 1.60 (3H, br s), 1.61 (3H, br s), 1.59–1.66
(2H, complex), 1.76 (3H, br s), 1.96–2.20 (10H, complex), 2.70 (1H, t,
J ¼ 6:4), 3.46 (2H, d, J ¼ 6:8 Hz), 5.13 (1H, t, J ¼ 5:6 Hz), 5.15 (1H,
t, J ¼ 6:0 Hz), 5.45 (1H, t, J ¼ 6:8 Hz), 6.95 (1H, d, J ¼ 1:2 Hz), 7.10
(1H, t, J ¼ 7:7 Hz), 7.18 (1H, t, J ¼ 7:7 Hz), 7.35 (1H, d, J ¼ 7:7 Hz),
oil According to the method of Ceruti et al.21) IR ꢁmax (film) cmꢁ1
:
2960, 2930, 2856, 1428, 1379, 1111, 1055, 701, 502. NMR ꢀH (CDCl3,
400 MHz): 1.04 (9H, s), 1.32 (3H, br s), 1.33 (3H, br s), 1.44 (3H, br s),
1.59 (3H, br s), 1.60 (3H, br s), 1.78 (1H, m), 1.92–2.14 (10H,
complex), 2.31 (1H, m), 3.96 (1H, d, J ¼ 11:6 Hz), 4.22 (2H, d,
J ¼ 6:2 Hz), 5.12 (1H, t, J ¼ 6:8 Hz), 5.20 (1H, t, J ¼ 6:4 Hz), 5.38
(1H, t, J ¼ 6:2 Hz), 7.34–7.45 (6H, 6 ꢂ ArH), 7.65–7.70 (4H,