2076 J . Org. Chem., Vol. 65, No. 7, 2000
Bringmann et al.
[M+ - CH3], 538 (9); HRMS calcd for C38H46NO4 580.3427,
found: 580.3422.
(1H, d, J ) 2.5 Hz), 7.16-7.35 (5H, m); 13C NMR (CDCl3, 50
MHz) δ 19.08, 20.23, 22.00, 22.05, 22.16, 31.09, 45.76, 50.04,
51.36, 64.73, 69.70, 69.84, 73.69, 101.19, 115.58, 116.55,
123.19, 126.34, 127.97, 128.62, 131.92, 133.49, 135.79, 140.94,
141.10, 153.72, 155.33, 157.17; MS (EI) m/z 531 (0.4) [M+], 516
(49) [M+ - CH3], 474 (7), 414 (8), 91 (100); HRMS calcd for
(B) F r om Kor u p en sa m in e B (1b). To a suspension of 1b
(50.0 mg, 106 µmol) and K2CO3 (23.2 mg, 234 µmol) in 5 mL
of acetone was added benzyl bromide (30 µL, 253 µmol) slowly
over a period of 2.5 h at room temperature. The reaction
mixture was purified by evaporation of the solvent in vacuo
and subsequent chromatography on deactivated (7.5% NH3)8
silica gel (petroleum ether/ethyl acetate ) 100:20 f 100:50).
The crude product (11.2 mg, 24.0 µmol) and Cs2CO3 (23.6 mg,
71.9 µmol) and i-PrBr (6.72 µL, 71.9 µmol) were added in each
case, after a total of 29 h the solvent was removed in vacuo,
and the residue was filtered on deactivated (7.5% NH3)8 silica
gel. The residue was dissolved in 1 mL of CH2Cl2 and after
addition of i-PrBr (6.72 µL, 71.9 µmol), 1 mL of an aqueous
KOH solution (5.0 n), and benzyltri-n-butylammonium chloride
(1 mg) the reaction was stirred for 48 h at room temperature.
The organic phase was separated and the aqueous phase was
extracted several times with CH2Cl2. After evaporation of the
solvent of the combined organic layers, the residue was
purified by chromatography on deactivated (7.5% NH3)8 silica
gel (CH2Cl2/MeOH ) 100:0.1 f 100:5) to give 20b (6.16 mg,
43%) as an amorphous solid. The compound was found to be
identical with the material obtained above, from the total
C33H42NO4 516.3114, found: 516.3111. Anal. Calcd for C34H45
-
NO4: C, 76.80; H, 8.53; N, 2.63. Found: C, 77.40; H, 8.37; N,
2.88.
(1R,3R,5P )-N-Ben zyl-5-(2′-for m yl-4′-isopr opoxy-1′-ph en -
yl)-6,8-d iisop r op oxy-1,3-d im eth yl-1,2,3,4-tetr a h yd r oiso-
qu in olin e (15a ). The synthesis of 15a from 14a (90%) was
achieved following the protocol for the preparation of 15b from
14b (see above): [R]23 ) +151.7 (c 0.35, CHCl3); IR (KBr) ν
D
2940, 2900, 1670, 1570 cm-1
;
1H NMR (CDCl3, 200 MHz) δ
1.05-1.10 (9H, m), 1.24 (3H, d, J ) 6.1 Hz), 1.32 (3H, d, J )
6.0 Hz), 1.35 (3H, d, J ) 6.7 Hz), 1.40 (6H, d, J ) 6.1 Hz),
1.95 (1H, dd, J ) 17.3 Hz, J ) 10.9 Hz), 2.27 (1H, dd, J )
17.5 Hz, J ) 4.5 Hz), 3.21 (1H, d, J ) 14.0 Hz), 3.41 (1H, mc),
3.72 (1H, d, J ) 14.1 Hz), 3.95 (1H, q, J ) 6.7 Hz), 4.24 (1H,
sept, J ) 6.1 Hz), 4.51 (1H, sept, J ) 6.0 Hz), 4.69 (1H, sept,
J ) 6.0 Hz), 6.39 (1H, s), 7.15-7.17 (2H, m), 7.21-7.36 (5 H,
m), 7.48 (1H, d, J ) 1.9 Hz), 9.65 (1H, s); 13C NMR (CDCl3, 50
MHz) δ 19.19, 20.22, 22.04, 22.11, 31.54, 45.78, 50.04, 51.37,
69.73, 70.02, 71.08, 98.31, 110.87, 118.69, 121.52, 123.07,
126.34, 127.97, 128.56, 133.27, 134.73, 135.36, 135.82, 141.08,
154.41, 155.86, 156.97, 193.16; MS (EI) m/z 529 (0.3) [M+], 514
(48) [M+ - CH3], 472 (8), 430 (10), 91 (100); HRMS calcd for
synthesis. [R]25 ) +34.1 (c 0.21, CHCl3).
D
N-Ben zylk or u p en sa m in e B (21b). To a solution of 20b
(6.00 mg, 10.1 µmol) in 1 mL of dry CH2Cl2 was added BCl3
(20.0 µL) at 0 °C. After stirring for 1 h at room temperature,
MeOH was added and the solvent was removed under reduced
pressure. Purification of the residue on deactivated (7.5%
NH3)8 silica gel (CH2Cl2/MeOH ) 100:3) afforded 21b as a
C
33H40NO4 514.2957, found: 514.2959.
(1R,3R,5P )-N-Ben zyl-5-(4′-h yd r oxy-2′-h yd r oxym eth yl-
5′-isopr opoxy-8′-n aph th yl)-6,8-diisopr opoxy-1,3-dim eth yl-
1,2,3,4-tetr a h yd r oisoqu in olin e (18a ). The diol 18a was
synthesized from 15a (41%) in analogy to the synthesis of 18b
slightly yellow gum (3.22 mg, 68%): [R]24 ) +86.3 (c 0.35,
D
MeOH); IR (KBr) ν 3600-3100, 2940, 2900, 1600, 1570 cm-1
;
1H NMR (CDCl3, 200 MHz) δ 1.07 (3H, d, J ) 6.5 Hz), 1.41
(3H, d, J ) 6.7 Hz), 1.85 (1H, dd, J ) 17.5 Hz, J ) 4.1 Hz),
2.19 (1H, dd, J ) 17.4 Hz, J ) 11.2 Hz), 2.38 (3H, s), 3.33
(1H, d, J ) 13.9 Hz), 3.33 (1H, mc), 3.79 (1H, d, J ) 13.9 Hz),
3.98 (1H, q, J ) 6.7 Hz), 4.09 (3H, s), 6.34 (1H, s), 6.68 (1H,
s), 6.85 (1H, s), 6.92 (1H, d, J ) 7.9 Hz), 7.22-7.40 (6H, m),
9.52 (1H, s); 13C NMR (CDCl3, 50 MHz) δ 18.45, 19.32, 22.28,
30.32, 47.84, 50.53, 53.04, 56.26, 101.01, 107.00, 109.96,
114.00, 115.08, 116.87, 117.85, 121.30, 127.88, 128.50, 130.00,
131.48, 133.02, 135.74, 137.02, 153.25, 154.83, 155.16, 156.45;
MS (EI) m/z 469 (1) [M+], 454 (94) [M+ - CH3], 424 (11), 91
(100); HRMS calcd for C30H28NO4 454.2018, found: 454.2018.
Kor u p en sa m in e B (1b). A mixture of 21b (4.74 mg, 10.1
µmol) and 1.00 mg of Pd/C (10%) in 1 mL of dry MeOH was
hydrogenated for 3 h under normal H2 pressure. After filtration
of the catalyst through Celite, the solvent was removed in
vacuo. MPLC with MeOH/H2O (8:2) at a pressure of 5 bar (10
mL/min) yielded 1b as an amorphous, brown solid (2.76 mg,
72%): [R]23D ) +70.3 (c 0.09, MeOH) (lit.3 +65, c 0.76, MeOH);
IR (KBr) ν 3600-3200, 2940, 1600, 1570 cm-1; 1H NMR (CD3-
OD, 200 MHz) δ 1.13 (3H, d, J ) 6.4 Hz), 1.59 (3H, d, J ) 6.7
Hz), 2.09 (1H, dd, J ) 17.4 Hz, J ) 4.7 Hz), 2.30 (1H, dd, J )
17.2 Hz, J ) 11.1 Hz), 2.31 (3H, s), 3.40 (1H, mc), 4.03 (3H, s),
4.59 (1H, q, J ) 6.7 Hz), 6.41 (1H, s), 6.75 (1H, s), 6.75 (1H, d,
J ) 7.7 Hz), 6.80 (1H, s), 7.02 (1H, d, J ) 7.8 Hz); MS (EI) m/z
379 (6) [M+], 364 (100) [M+ - CH3], 349 (9), 334 (27). The
compound was found to be fully identical with an authentic
sample of korupensamine B (1b) from A. korupensis.3
from 15b via 17b: [R]21 ) +74.5 (c 0.40, CHCl3); IR (KBr) ν
D
3600-3100, 2960, 2910, 1590, 1570 cm-1; 1H NMR (CDCl3, 200
MHz) δ 0.91 (3H, d, J ) 6.1 Hz, 1.00 (3H, d, J ) 6.6 Hz), 1.02
(3H, d, J ) 6.1 Hz), 1.29 (3H, d, J ) 6.1 Hz), 1.34 (3H, d, J )
6.0 Hz), 1.37 (3H, d, J ) 6.6 Hz), 1.55 (3H, d, J ) 6.1 Hz),
1.56 (3H, d, J ) 6.1 Hz), 1.96 (1H, dd, J ) 17.8 Hz, J ) 10.7
Hz), 2.12 (1H, dd, J ) 17.6 Hz, J ) 4.9 Hz), 3.26 (1H, d, J )
14.1 Hz), 3.35 (1H, mc), 3.70 (1H, d, J ) 14.3 Hz), 3.98 (1H, q,
J ) 6.7 Hz), 4.11 (1H, sept, J ) 6.1 Hz), 4.55 (1H, sept, J )
6.4 Hz), 4.63 (2H, br), 4.91 (1H, sept, J ) 6.0 Hz), 6.47 (1H,
s), 6.82 (1H, s), 6.84 (1H, s), 6.87 (1H, d, J ) 8.5 Hz), 7.16
(1H, d, J ) 7.9 Hz), 7.21-7.38 (5H, m), 9.97 (1H, s); 13C NMR
(CDCl3, 50 MHz) δ 19.25, 20.26, 22.04, 22.11, 22.21, 22.25,
22.36, 30.19, 45.76, 49.95, 51.62, 65.60, 69.60, 71.93, 72.78,
99.96, 106.45, 108.59, 114.53, 115.57, 121.61, 122.34, 126.33,
128.00, 128.12, 128.57, 129.30, 136.20, 136.40, 140.08, 141.26,
153.15, 154.79, 155.41, 155.50; MS (EI) m/z 597 (1) [M+], 582
(30) [M+ - CH3], 516 (17), 91 (100); HRMS calcd for C37H44
-
NO5 582.3219, found: 582.3219.
(1R,3R,5P )-N-Ben zyl-5-(4′-h yd r oxy-5′-isop r op oxy-2′-
m eth yl-8′-n aph th yl)-6,8-diisopr opoxy-1,3-dim eth yl-1,2,3,4-
tetr a h yd r oisoqu in olin e (19a ). The preparation of 19a from
18a (63%) was performed in analogy to the synthesis of 19b
from 18b reported above: [R]24 ) +97.5 (c 0.37, CHCl3); IR
D
(KBr) ν 3600-3100, 2950, 2900, 1580, 1570 cm-1
;
1H NMR
(CDCl3, 200 MHz) δ 0.90 (3H, d, J ) 6.1 Hz), 1.00 (3H, d, J )
6.6 Hz), 1.03 (3H, d, J ) 6.1 Hz), 1.29 (3H, d, J ) 6.0 Hz),
1.34 (3H, d, J ) 6.1 Hz), 1.38 (3H, d, J ) 6.8 Hz), 1.54 (3H, d,
J ) 6.1 Hz), 1.55 (3H, d, J ) 6.1 Hz), 2.00 (1H, dd, J ) 17.6
Hz, J ) 10.6 Hz), 2.14 (1H, dd, J ) 17.6 Hz, J ) 5.4 Hz), 2.30
(3H, s), 3.26 (1H, d, J ) 14.2 Hz), 3.36 (1H, mc), 3.72 (1H, d,
J ) 14.2 Hz), 3.99 (1H, q, J ) 6.8 Hz), 4.09 (1H, sept, J ) 6.0
Hz), 4.55 (1H, sept, J ) 6.2 Hz), 4.90 (1H, sept, J ) 6.2 Hz),
6.48 (1H, s), 6.62 (1H, br), 6.68 (1H, d, J ) 1.4 Hz), 6.80 (1H,
d, J ) 8.1 Hz), 7.11 (1H, d, J ) 7.9 Hz), 7.18-7.39 (5H, m),
9.86 (1H, s); 13C NMR (CDCl3, 50 MHz) δ 19.23, 20.40, 21.90,
22.05, 22.14, 22.25, 22.37, 30.07, 45.81, 49.98, 51.75, 69.55,
72.10, 72.63, 100.27, 105.56, 111.62, 114.32, 116.34, 121.64,
122.89, 126.33, 127.75, 128.00, 128.57, 136.30, 136.53, 137.15,
141.43, 153.19, 154.73, 154.85, 155.39; MS (EI) m/z 581 (1)
[M+], 566 (84) [M+ - CH3], 524 (13), 482 (8), 91 (100); HRMS
calcd for C37H44NO4 566.3270, found: 582.3261.
(1R,3R,5P )-N-Ben zyl-5-(2′-h ydr oxym eth yl-4′-isopr opoxy-
1′-p h en yl)-6,8-d iisop r op oxy-1,3-d im eth yl-1,2,3,4-tetr a h y-
d r oisoqu in olin e (14a ). The preparation of 14a from 10a
(76%) was performed in analogy to the synthesis of 14b
described above: [R]24 ) +157.8 (c 0.32, CHCl3); IR (KBr) ν
D
3600-3200, 2940, 2900, 1570 cm-1; 1H NMR (CDCl3, 200 MHz)
δ 0.91 (3H, d, J ) 6.1 Hz), 1.09 (3H, d, J ) 6.6 Hz), 1.18 (3H,
d, J ) 6.1 Hz), 1.23 (3H, d, J ) 6.1 Hz), 1.30-1.40 (12H, m),
1.84 (1H, dd, J ) 17.7 Hz, J ) 10.9 Hz), 2.34 (1H, dd, J )
17.7 Hz, J ) 4.6 Hz), 3.07 (1H, br), 3.18 (1H, d, J ) 14.0 Hz),
3.41 (1H, mc), 3.71 (1H, d, J ) 13.9 Hz), 3.95 (1H, q, J ) 6.6
Hz), 4.11 (1H, sept, J ) 6.1 Hz), 4.22 (2H, br), 4.49 (1H, sept,
J ) 6.1 Hz), 4.63 (1H, sept, J ) 6.1 Hz), 6.43 (1H, s), 6.89
(1H, dd, J ) 8.3 Hz, J ) 2.6 Hz), 7.00 (1H, d, J ) 8.3 Hz), 7.07