and 5-H), 7.25 (1H, td, J 7.7, 1.5, 4-H) and 7.82 (1H, dd, J 1.6,
8.3, 6-H); δC (100 MHz; CDCl3) 12.6 (CH3, NCH2CH3), 20.5
(CH2, C-13Ј), 23.9 (CH2, C-3Ј), 29.8 (CH2, C-2Ј), 30.4 (CH2,
C-12Ј), 35.7 (CH2, C-6Ј), 35.8 (CH2, C-14Ј), 41.7 (quat., C-1Ј),
42.2 (quat., C-8Ј), 52.4 (CH2, NCH2CH3), 58.8 (CH2, C-11Ј),
61.7 (CH2, C-9Ј), 68.0 (CH2, OCH2), 74.1 (quat., C-7Ј), 110.9
(quat., C-1), 116.2 (CH, C-3), 116.7 (CH, C-5), 126.5 (CH,
C-5Ј), 131.0 (CH, C-6), 133.9 (CH, C-4), 136.1 (CH, C-4Ј),
and 13ЉA-H), 2.89 (1H, d, Jgem 11.4, 9ЉA-H), 3.04–3.18 (2H, m,
4Ј-CH2), 3.32 (1H, s, OH), 4.28 (2H, br s, OCH2), 5.46–5.61
(1H, m, 5Љ-H), 6.00–6.16 (1H, m, 4Љ-H), 7.24 (1H, d, J 7.3, 3-H),
7.53 (1H, t, J 7.6, 5-H), 7.65 (1H, t, J 7.5, 4-H) and 8.08 (1H, d,
J 7.7, 6-H); δC (50 MHz; CDCl3) 11.8 (CH3, NCH2CH3), 19.4
(CH2, C-13Љ), 23.0 (CH2, C-3Љ), 29.9 (CH2, C-12Љ), 31.4
(CH2, C-6Љ), 32.4 (CH2, C-2Љ and C-14Љ), 35.3 (CH, C-3Ј), 37.0
(CH2, C-4Ј), 42.3 (quat., C-1Љ), 42.4 (quat., C-8Љ), 53.0 (CH2,
NCH2CH3), 56.7 (CH2, C-11Љ), 61.2 (CH2, C-9Љ), 69.0 (CH2,
OCH2), 72.7 (quat., C-7Љ), 126.4 (CH, C-5Љ), 127.2 (quat., C-1),
129.5 (CH, C-3), 130.0 (CH, C-5), 131.3 (CH, C-4), 132.8.4
(quat., C-2), 133.4 (CH, C-6), 136.5 (CH, C-4Љ), 164.2 (quat.,
150.4 (quat., C-2) and 168.1 (quat., OC᎐O); m/z (EI) 384
᎐
(Mϩ, 17%), 369 (M Ϫ CH3, 49), 367 (M Ϫ OH, 9), 264
(M Ϫ NH2C6H4CO, 10) and 120 (NH2C6H4CO, 100).
(1ЈS*,7ЈS*,8ЈS*)-(10-Ethyl-7-hydroxy-10-azatricyclo-
[6.3.3.01,7]tetradec-4-en-8-yl)methyl 2-aminobenzoate (28)
OC᎐O), 175.9 (quat., C-5Ј) and 179.9 (quat., C-2Ј); m/z (EI) 480
᎐
(Mϩ, 25%), 465 (M Ϫ CH3, 100) and 188 (C11H10NO2, 10).
The reaction was carried out according to the standard pro-
cedure, with the esterification step being left for 48 h, using
(1S*,7S*,8S*)-10-ethyl-8-(hydroxymethyl)-10-aza-
(1ЉS*,7ЉS*,8ЉS*,3ЈR*)- and (1ЉS*,7ЉS*,8ЉS*,3ЈR*)-(10-Ethyl-7-
hydroxy-10-azatricyclo[6.3.3.01,7]tetradec-4-en-8-yl)methyl 2-
(3-methyl-2,5-dioxopyrrolidin-1-yl)benzoate (30)
tricyclo[6.3.3.01,7]tetradec-4-en-7-ol 26 (173 mg, 0.652 mmol),
N-(trifluoroacetyl)anthranilic acid 15 (456 mg, 1.96 mmol),
4-(dimethylamino)pyridine (39 mg, 0.33 mmol), 1,3-dicyclo-
hexylcarbodiimide (404 mg, 1.96 mmol) and sodium boro-
hydride (49 mg, 1.30 mmol). Flash chromatography with 4 : 1
hexane–ethyl acetate as eluent afforded the title compound 28
(181 mg, 72%) as a pale yellow oil [Found (EI): Mϩ; 384.2405;
C23H32N2O3 requires Mϩ, 384.2413]; νmax(NaCl)/cmϪ1 3501
(1ЈS*,7ЈS*,8ЈS*)-(10-Ethyl-7-hydroxy-10-azatricyclo-
[6.3.3.01,7]tetradec-4-en-8-yl)methyl 2-aminobenzoate 28 (117
mg, 0.304 mmol) and methylsuccinic anhydride (104 mg,
0.913 mmol) were heated together at 125 ЊC for 3 h. After this
time the crude mixture was dissolved in warm ethyl acetate
(10 mL), washed with sat. sodium bicarbonate (30 mL), brine
(30 mL), dried (MgSO4) and concentrated in vacuo. Purification
by flash chromatography using 100% ethyl acetate as eluent
afforded the title compound 30 (120 mg, 82%) as a yellow
oil [Found (EI): Mϩ, 480.2618; C28H36N2O5 requires Mϩ,
480.2624]; νmax(NaCl)/cmϪ1 3301 (O–H), 2929 (C–H), 1777 (N-
C᎐O), 1714 (C᎐O), 1602, 1493, 1454 and 1260; δ (200 MHz;
(O–H), 3474 and 3368 (N–H), 2917 (C–H), 1686 (C᎐O), 1616,
᎐
1587, 1560, 1453 and 1245; δH (200 MHz; CDCl3) 0.97 (1H,
ddd, J12A,13B 2.0, J12A,13A 5.9, Jgem 14.5, 12A-H), 1.04 (3H, t,
J 7.2, NCH2CH3), 1.22–1.41 (2H, m, 12ЈB-H and 13ЈB-H),
1.47–2.05 (5H, m, 3ЈA-H or 3ЈB-H, 2Ј-CH2 and 14Ј-CH2), 2.21–
2.39 (4H, m, 3ЈA-H or 3ЈB-H, 6ЈA-H or 6ЈB-H, 11ЈB-H and
NCH2CH3), 2.42 (1H, d, Jgem 11.2, 11ЈA-H), 2.62 (1H, dd,
J9ЈB,11ЈB 1.5, Jgem 10.8, 9ЈB-H), 2.77 (1H, d, Jgem 10.8, 9ЈA-H),
2.81–2.93 (3H, m, 6ЈA-H or 6ЈB-H, 13ЈA-H and OH), 4.27 (1H,
d, Jgem 11.2, OCHAHB), 4.27 (1H, d, Jgem 11.4, OCHAHB), 5.52–
5.64 (1H, m, 5Ј-H), 5.74 (2H, br, NH2), 6.00–6.13 (1H, m,
4Ј-H), 6.61–6.68 (2H, m, 3-H and 5-H), 7.25 (1H, td, J 7.6, 1.5,
4-H) and 7.82 (1H, dd, J 1.6, 8.2, 6-H); δC (50 MHz; CDCl3)
12.5 (CH3, NCH2CH3), 19.8 (CH2, C-13Ј), 23.1 (CH2, C-3Ј),
30.2 (CH2, C-12Ј), 31.4 (CH2, C-6Ј), 32.5 (CH2, C-14Ј), 32.8
(CH2, C-2Ј), 42.3 (quat., C-1Ј), 42.4 (quat., C-8Ј), 52.1 (CH2,
NCH2CH3), 57.5 (CH2, C-11Ј), 62.6 (CH2, C-9Ј), 68.2 (CH2,
OCH2), 73.2 (quat., C-7Ј), 111.0 (quat., C-1), 116.3 (CH, C-3),
116.7 (CH, C-5), 126.8 (CH, C-5Ј), 131.0 (CH, C-6), 134.0 (CH,
C-4), 136.1 (CH, C-4Ј), 150.4 (quat., C-2) and 168.1 (quat.,
᎐
᎐
H
CDCl3) 1.06 (3H, t, J 7.1, NCH2CH3), 1.13–1.70 (8H, m,
3Ј-CH3, 2ЉA-H or 2ЉB-H, 12Љ-CH2, 13ЉB-H and 14ЉB-H),
1.90–2.38 (9H, m, 2ЉA-H or 2ЉB-H, 3Љ-CH2, 6ЉA-H or 6ЉB-H,
7Љ-OH, 9ЉB-H, 14ЉA-H and NCH2CH3), 2.41–2.68 (4H, 3Ј-H,
6ЉA-H or 6ЉB-H and 11Љ-CH2), 2.70–2.94 (2H, m, 9ЉA-H and
13ЉA-H), 3.04–3.15 (2H, m, 4Ј-CH2), 4.15–4.29 (2H, m, OCH2),
5.49–5.54 (1H, m, 5Љ-H), 6.01–6.11 (1H, m, 4Љ-H), 7.23 (1H, dd,
J 1.9, 6.5, 3-H), 7.52 (1H, td, J 7.7, 1.3, 5-H), 7.65 (1H, td, J 7.4,
1.4, 4-H) and 8.09 (1H, d, J 6.6, 6-H); δC (50 MHz; CDCl3) 12.5
(CH3, NCH2CH3), 16.3 (CH3, 3Ј-CH3), 20.4 (CH2, C-13Љ), 23.8
(CH2, C-3Љ), 29.6 (CH2, C-2Љ), 29.8 (CH2, C-12Љ), 35.2 (CH2,
C-6Љ), 35.3 (CH2, C-14Љ), 35.9 (CH, C-3Ј), 36.9 (CH2, C-4Ј),
41.7 (quat., C-1Љ), 42.1 (quat., C-8Љ), 52.3 (CH2, NCH2CH3),
58.6 (CH2, C-11Љ), 61.6 (CH2, C-9Љ), 68.8 (CH2, OCH2), 73.9
(quat., C-7Љ), 126.2 (CH, C-5Љ), 127.2 (quat., C-1), 129.3 (CH,
C-3), 129.7 (CH, C-5), 131.2 (CH, C-4), 132.7 (quat., C-2) 133.3
OC᎐O); m/z (EI) 384 (Mϩ, 18%), 367 (M Ϫ OH, 5), 264
᎐
(CH, C-6), 136.3 (CH, C-4Љ), 164.2 (quat., OC᎐O), 175.8 (quat.,
(M Ϫ NH2C6H4CO, 17), 120 (NH2C6H4CO, 73) and 72 (100).
᎐
C-5Ј) and 179.8 (quat., C-2Ј); m/z (EI) 480 (Mϩ, 6%), 465
(M Ϫ CH3, 20), 188 (C11H10NO2, 2) and 146 (100).
(1ЉS*,7ЉR*,8ЉS*,3ЈR*)- and (1ЉS*,7ЉR*,8ЉS*,3ЈS*)-(10-Ethyl-7-
hydroxy-10-azatricyclo[6.3.3.01,7]tetradec-4-en-8-yl)methyl 2-
(3-methyl-2,5-dioxopyrrolidin-1-yl)benzoate (29)
Acknowledgements
(1ЈS*,7ЈR*,8ЈS*)-(10-Ethyl-7-hydroxy-10-azatricyclo-
We thank Ms Diana Lin for performing the NMR analysis
of compounds 6 and 7. Generous financial assistance from
Dunlena and an Australian Postgraduate Award (Industry) to
D. B. (C29804582) supported this work.
[6.3.3.01,7]tetradec-4-en-8-yl)methyl 2-aminobenzoate 27 (73
mg, 0.189 mmol) and methylsuccinic anhydride (65 mg, 0.569
mmol) were heated together at 125 ЊC for 12 h. After this time
the crude mixture was dissolved in warm ethyl acetate (10 mL),
washed with sat. sodium bicarbonate (30 mL), brine (30 mL),
dried (MgSO4) and concentrated in vacuo. Purification by flash
chromatography using 49 : 1 dichloromethane–methanol as
eluent afforded the title compound 29 (82 mg, 90%) as an orange
oil [Found (EI): Mϩ 480.2627; C28H36N2O5 requires Mϩ,
480.2624]; νmax(NaCl)/cmϪ1 3310 (O–H), 2924 (C–H), 1783
(N-C᎐O), 1715 (C᎐O), 1603, 1492, 1453, 1391 and 1260; δ (200
References
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J. Wiley and Sons, New York, 1984, vol. 2, p. 205.
2 S. W. Pelletier and B. S. Joshi. in Alkaloids: Chemical and Biological
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vol. 7, p. 297.
3 R. H. Manske, Can. J. Res., 1938, 16B, 57.
4 J. A. Goodson, J. Chem. Soc., 1943, 139.
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6 K. R. Jennings, D. G. Brown and D. P. Wright, Experientia, 1986, 42,
611.
᎐
᎐
H
MHz; CDCl3) 1.00 (1H, dd, J12ЉA,13ЉA 5.8, Jgem 14.3, 12ЉA-H),
1.10 (3H, t, J 7.1, NCH2CH3), 1.21–1.36 (2H, m, 12ЉB-H and
13ЉB-H), 1.45 (3H, br d, J 5.6, 3Ј-CH3), 1.53–2.03 (5H, m, 2Љ-
CH2, 3ЉA-H or 3ЉB-H and 14Љ-CH2), 2.26–2.53 (6H, m, 6ЉA-H
or 6ЉB-H, 3ЉA-H or 3ЉB-H, 11Љ-CH2 and NCH2CH3), 2.68 (1H,
d, Jgem 11.4, 9ЉB-H), 2.71–2.86 (3H, m, 6ЉA-H or 6ЉB-H, 3Ј-H
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 6 5 9 – 1 6 6 9
1668