P. Magnus et al. / Tetrahedron 58 *2002) 3423±3443
3441
7.23 4d, J8.2 Hz, 1H), 6.51 4d, J8.3 Hz, 1H), 4.61 4s,
1H), 3.97 4s, 3H), 3.95 4s, 3H), 3.93 4s, 3H), 3.42 4t, J
12 Hz, 1H), 3.14 4d, J12 Hz, 1H), 2.95 4t, J9 Hz, 1H),
2.84 4q, J9 Hz, 1H), 2.43 4dd, J15, 6 Hz, 1H), 2.05 4m,
4H), 1.71 4bm, 1H), 1.57 4bm, 1H), 1.35 4m, 2H), 1.00 4m,
1H). 13C NMR 4CDCl3, 75 MHz) d 164.4, 152.5, 143.7,
143.0, 135.3, 134.4, 127.1, 118.5, 103.5, 77.1, 70.8, 68.8,
65.8, 60.3, 55.8, 51.8, 49.8, 44.8, 41.5, 37.6, 31.8, 31.3,
27.4, 16.5. HRCIMS calcd for C24H28N2O4, 4MH1)
422.208. Found 422.208.
42H, d, J6.5 Hz), 7.20 44H, m), 6.74 41H, d, J8.3 Hz),
6.60 41H, s), 4.00 41H, t, J7.9 Hz), 3.90 43H, s), 3.85 46H,
br s), 3.83 43H, s), 3.23 41H, br t, J12.4 Hz), 2.98 42H, dd,
J14.1, 6.5 Hz), 2.81 41H, t, J8.4 Hz), 2.68 41H, q, J
8.3 Hz), 1.95 42H, m), 1.73 43H, m), 1.41 41H, br d, J
11.7 Hz). 13C NMR 475 MHz, CDCl3) d 166.0, 153.9,
153.7, 138.6, 138.3, 134.4, 133.8, 133.7, 129.4, 128.9,
128.5, 127.3, 118.1, 108.2, 75.4, 68.9, 67.4, 60.8, 56.1,
53.0, 52.4, 50.1, 44.5, 40.8, 40.6, 39.9, 38.6, 30.7, 15.6,
14.1. HRMS calcd for C32H34N3O6Se80 4MH1) 636.161.
Found 636.161.
10.1.45. ꢀ^)-16-Anhydro-1-decarbomethoxy-18-seleno-
phenyllahadinine B 61. A solution of 58 481 mg,
0.2061 mmol) in freshly distilled acryloyl chloride
42.0 mL) was stirred in a sealed tube at ambient temperature
in the dark for 24 h, and concentrated under reduced
pressure to yield a pale brown solid 59. The crude solid
was dissolved in CH2Cl2 42.0 mL, with 2.0 mL wash over)
and added to a suspension of pre-dried 2-mercaptopyridine
N-oxide sodium salt450 mg, 0.3017 mmol, etch., 90%) in
CH2Cl2 43.5 mL) at0 8C in the dark. The mixture was stirred
for 5 min, warmed to room temperature, stirred for a further
1.75 h, cooled to 08C and treated with a solution of diphenyl
diselenide 4371 mg, 1.19 mmol) in CH2Cl2 43.0 mL). The
yellow solution was irradiated with a tungsten lamp for
30 min 4the reaction temperature was kept between 0 and
208C). After irradiation the mixture was evaporated in
vacuo to give a yellow solid. Puri®cation by ¯ash column
chromatography over silica gel eluting with 50% EtOAc/
hexanes gave 61 as a colorless oil 449 mg, 41%). IR 4®lm)
10.1.47. ꢀ^)-18-Selenophenyllahadinine B 63. A dark
brown solution of 62 47 mg, 0.0110 mmol) and tris4dipiva-
loylmethanato)manganese4III) 43 mg, 0.0071 mmol) in iso-
propanol 40.2 mL) and 1,2-dichloroethane 40.5 mL) at 08C
was treated with phenylsilane 450 mL, 0.402 mmol) causing
the mixture to turn pale brown. The solution was placed
under an atmosphere of oxygen and stirred for a further
10 min at0 8C. The mixture was warmed to room tempera-
ture and stirred for 7 days. The solution was treated with
aqueous 1 M Na2S2O3 43 mL) and extracted with CH2Cl2
45£10 mL). The combined extracts were dried 4Na2SO4),
®ltered and evaporated in vacuo to give a pale brown oil.
Puri®cation by ¯ash column chromatography over silica gel
eluting with 50% EtOAc/hexanes gave 63 46 mg, 83%). Mp
2498C 4dec). IR 4®lm) 3351, 2948, 2362, 1740, 1680 cm21
.
13C NMR 475 MHz, CDCl3) d 172.4, 153.7, 138.8, 133.0,
132.8, 130.8, 130.7, 128.8, 126.1, 117.9, 117.4, 107.8, 79.3,
74.1, 67.9, 62.5, 60.0, 56.2, 53.5, 52.3, 49.1, 44.3, 43.4,
41.3, 40.2, 38.9, 37.6, 32.2, 29.6, 20.7. HRMS calcd for
C32H36N3O7Se80 4MH1) 654.172. Found 654.172. Used
directly in the next stage.
1
3380, 2943, 2859, 2839, 2251, 1718, 1622, 1578 cm21. H
NMR 4300 MHz, CDCl3) d 7.37 42H, d, J7.6 Hz), 7.20
43H, m), 7.08 41H, d, J8.2 Hz), 7.05 41H, s), 6.40 41H, d,
J8.2 Hz), 3.88 43H, s), 3.82 43H, s), 3.75 43H, s), 3.29 41H,
br t, J12.2 Hz), 3.02 41H, br d, J13.7 Hz), 2.83 41H, t,
J7.6 Hz), 2.71 41H, q, J8.3 Hz), 2.52 41H, dd, J14.0,
8.6 Hz), 2.36 41H, dd, J14.2, 7.2 Hz), 1.95 42H, m), 1.85
42H, m), 1.50 42H, m). 13C NMR 475 MHz, CDCl3) d 164.1,
152.7, 144.0, 142.2, 134.7, 134.1, 133.8, 129.1, 128.3,
127.7, 126.4, 118.3, 118.1, 104.1, 73.9, 68.5, 67.0, 60.3,
55.9, 52.0, 49.6, 44.6, 43.3, 41.9, 41.5, 38.1, 30.8, 16.1.
HRMS calcd for C30H32N3O4Se80 4MH1) 578.156. Found
578.152.
10.1.48. ꢀ^)-Lahadinine B 64. A solution of 63 47 mg,
0.011 mmol) in toluene 40.75 mL) heated at re¯ux was
treated with a solution of triphenyltin hydride 418 mg,
0.051 mmol) in toluene 40.75 mL), and stirred for a period
of 24 h in the dark. The cooled mixture was evaporated in
vacuo, and puri®ed by ¯ash column chromatography over
silica gel eluting with 50% EtOAc/hexanes to give 64
46 mg, 83%) as a white solid. Crystallization by slow
evaporation from a solution in CH2Cl2/MeOH 42:1, v/v)
gave 64 as colorless needles suitable for X-ray crystal-
lography. IR 4®lm) 2917, 2848, 2352, 1738, 1732, 1714,
10.1.46. ꢀ^)-16-Anhydro-18-selenophenyllahadinine B
62. A solution of 61 417 mg, 0.0295 mmol) and 18-crown-
6 412 mg, 0.0454 mmol) in THF 41.0 mL) at 2788C, under
argon, was treated with a solution of KN4SiMe3)2
40.088 mL, 0.0442 mmol, 1.0 M solution in toluene) to
give an orange-brown solution. The solution was stirred
for a further 10 min, and CO2 gas was passed over the
mixture for 10 min to give a pale yellow solution. The
CO2 inletwas removed, dimhetyl sulfeat 40.012 mL,
0.127 mmol) was added, and stirring continued for 15 min
at 2788C. The mixture was allowed to warm to room
temperature, stirred for a further 30 min and treated with
pH 7 phosphate buffer solution 45 mL). The mixture was
extracted with CH2Cl2 45£15 mL), and the combined
extracts were dried 4Na2SO4), ®ltered, and evaporated in
vacuo to give a pale brown oil. Puri®cation by ¯ash column
chromatography over silica gel eluting with 50% EtOAc/
hexanes gave 62 416 mg, 86%). IR 4®lm) 2948, 2858, 2251,
1802, 1718, 1610 cm21. 1H NMR 4300 MHz, CDCl3) d 7.34
1
1694, 1682, 1651 cm21. H NMR 4500 MHz, CDCl3) d
7.14 41H, d, J8.2 Hz), 6.61 41H, d, J8.4 Hz), 6.60 41H,
d, J0.6 Hz), 3.87 43H, s), 3.84 43H, s), 3.73 43H, s), 3.72
43H, s), 3.04 44H, m), 2.92 41H, ddd, J9.0, 6.6, 1.8 Hz),
2.39 41H, ddd, J13.4, 10.8, 1.6 Hz), 1.98 41H, ddd, J
12.2, 9.2, 6.8 Hz), 1.87 41H, ddd, J12.8, 10.2, 9.0 Hz),
1.73 41H, ddd, J13.4, 10.5, 8.3 Hz), 1.70 41H, m), 1.56
45H, m), 1.43 41H, m). 13C NMR 4125 MHz, CDCl3) d
172.5, 157.0, 153.6, 137.9, 133.7, 130.2, 118.5, 117.9,
106.9, 75.3, 73.7, 68.4, 60.1, 59.6, 56.0, 53.5, 52.4, 49.1,
44.3, 39.5, 39.2, 36.7, 32.5, 28.3, 24.9, 20.3. HRMS calcd
for C26H32N3O7 4MH1) 498.224. Found 498.225 4Fig. 1).
10.1.49. ꢀ^)-11-Methoxykopsilongine 65. A solution of
lahadinine B 64 43.5 mg) in dichloromethane 41.3 mL) at
08C under an atmosphere of argon was treated with tri-
¯uoroacetic acid 4450 mL) to give a very pale green/
brown solution. After stirring for a further 5 min the mixture