Synthesis of (-)-Dendroprimine
J ournal of Natural Products, 2004, Vol. 67, No. 6 1031
mixture of 5a and 6a in a 4:1 ratio. These isomers could not
be separated by flash column chromatography. The mixture
was purified by flash column chromatography on silica gel
(ethyl acetate): anal. C 72.97%, H 9.20%, N 8.00%, calcd for
(2H, m, H-7, H-2b), 1.50-1.35 (2H, m, H-6a, H-6b), 1.35-1.20
(1H, m, H-8b), 0.92 (3H, d, J ) 6.7 Hz, NCHCH3), 0.85 (3H, d,
J ) 6.4 Hz, CHCH3), 0.75 (1H, m, H-1b); 13C NMR (CDCl3) δ
54.2 (CH, C-5), 49.9 (CH, C-9), 48.6 (CH2, C-3), 40.6 (CH2, C-1),
40.0 (CH2, C-6), 30.8 (CH2, C-8), 25.6 (CH, C-7), 22.4 (CH3,
CHCH3), 21.1 (CH2, C-2), 9.7 (CH3, NCHCH3).
C
10H15NO, C 72.73%, H 9.09%, N 8.48%.
5a : H NMR (CDCl3) δ 4.83 (1H, s), 4.72 (1H, s), 4.40 (1H,
1
m), 3.60-3.45 (1H, m), 2.45-1.40 (8H, m), 1.00 (3H, d, J )
7.4 Hz); 13C NMR (CDCl3) δ 174.1 (C), 141.9 (C), 113.3 (CH2),
54.8 (CH), 45.0 (CH), 43.0 (CH2), 39.6 (CH2), 31.3 (CH2), 25.9
(CH2), 19.3 (CH3).
(5R,7S,9R)-10a : [R]25 -37.5 (c 1.3, CHCl3) [lit.1 [R]D -38
D
1
(c 1.00, CHCl3)]; H NMR (CDCl3) δ 3.18 (1H, m, H-9), 3.10
(1H, m, H-3a), 2.80 (1H, m, H-3b), 2.38 (1H, m, H-5), 1.9-1.5
(8H, m), 1.00 (3H, d, J ) 6.0 Hz, NCHCH3), 0.95-0.90 (1H,
m, H-8), 0.88 (3H, d, J ) 6.3 Hz, CHCH3); 13C NMR (CDCl3) δ
60.8 (CH, C-9), 51.7 (CH2, C-3), 50.6 (CH, C-5), 43.7 (CH2, C-8),
35.9 (CH2, C-1), 27.4 (CH2, C-6), 26.1 (CH, C-7), 22.9 (CH3,
CHCH3), 22.7 (CH2, C-2), 22.6 (CH3, NCHCH3).
6a : 1H NMR (CDCl3) δ 4.80 (1H, s), 4.73 (1H, s), 3.60-3.45
(2H, m), 2.50 (1H, dd, J ) 15.4, 3.0 Hz), 2.45-1.40 (7H, m),
1.38 (3H, d, J ) 7.4 Hz); 13C NMR (CDCl3) δ 175.6 (C), 142.5
(C), 112.2 (CH2), 58.4 (CH), 50.4 (CH), 40.5 (CH2), 40.4 (CH2),
32.6 (CH2), 26.9 (CH2), 20.7 (CH3).
(5R,7R,9S)-11a : [R]25 -32.8 (c 0.4, CHCl3); 1H NMR
D
Red u ction of th e La cta m F u n ction a l Gr ou p . A mixture
of lactam (0.2 g, 0.0012 mol) and LiAlH4 (0.16 g, 0.0042 mol)
in dry THF (10 mL) was refluxed for 12 h. Ether was added,
followed by water (0.16 mL), 10% NaOH (0.16 mL), and water
(0.48 mL). After filtration, the organic layer was dried and
concentrated to give the crude reduction product in quantita-
tive yield. It was purified by flash chromatography (ethyl
ether).
Ca ta lytic Hyd r ogen a tion of th e Olefin ic Bon d . Meth-
yleneindolizidine (0.2 g) was dissolved in methanol (10 mL),
and catalyst (0.2 g Pd/C or 0.05 g PtO2) was added. The
resultant mixture was stirred under 1 atm of hydrogen at room
temperature for 5 h in a Parr apparatus. The catalyst was
removed by filtration through a Celite pad, and the solvent
was evaporated. The crude product was purified by flash
chromatography (ethyl ether).
(CDCl3) δ 3.30 (1H, td, J ) 2.8, 8.6 Hz, H-9), 2.30-1.40 (11H,
m), 1.10 (3H, d, J ) 6.4 Hz), 1.05-0.95 (1H, m), 0.90 (3H, d,
J ) 6.4 Hz); 13C NMR (CDCl3) δ 64.7 (CH), 58.1 (CH), 51.4
(CH2), 43.1 (CH2), 39.5 (CH2), 31.3 (CH), 30.3 (CH2), 21.9 (CH3),
21.6 (CH3), 21.0 (CH2).
(5S,7S,9S)-9b: [R]25 -6.9 (c 1.0, CHCl3).
D
(5S,7R,9S)-10b: [R]25 +36.8 (c 1.2, CHCl3).
D
(5S,7S,9R)-11b: [R]25 +33.7 (c 2.0, CHCl3).
D
1
5,7-Dim eth ylin d olizid in -3-on es. 12: H NMR (CDCl3) δ
4.30 (1H, m, H-5), 3.52 (1H, m, H-9), 2.23 (2H, m), 2.10 (1H,
m), 1.75 (2H, m), 1.45 (3H, m), 1.05 (3H, d, J ) 7.0 Hz,
NCHCH3), 0.86 (3H, d, J ) 6.4 Hz, CHCH3), 0.72 (1H, m,
H-8a); 13C NMR (CDCl3) δ 173.2 (C, CO), 53.0 (CH, C-9), 43.4
(CH, C-5), 42.2 (CH2, C-8), 38.1 (CH2), 30.6 (CH2), 25.4 (CH2),
25.1 (CH), 21.9 (CH3, CHCH3), 16.6 (CH3, NCHCH3).
13: 1H NMR (CDCl3) δ 4.05 (1H, m, H-5), 3.72 (1H, m, H-9),
2.3-1.3 (8H, m), 1.10-0.90 (1H, m), 1.12 (3H, d, J ) 6.9 Hz,
NCHCH3), 1.01 (3H, d, J ) 7.1 Hz, CHCH3); 13C NMR (CDCl3)
δ 173.8 (C, CO), 48.9 (CH, C-9), 44.5 (CH, C-5), 38.9 (CH2),
36.0 (CH2), 30.4 (CH2), 25.9 (CH), 25.8 (CH2), 20.9 (CH3,
CHCH3), 19.8 (CH3, NCHCH3).
5-Meth yl-7-m eth ylen ein d olizid in es. (5R,9R)-7a : 50%
yield; [R]25 +8.0 (c 1.0, CHCl3); 1H NMR (CDCl3) δ 4.77 (1H,
D
q, J ) 1.8 Hz, CdCH2), 4.69 (1H, q, J ) 1.8 Hz, CdCH2), 3.30
(1H, d quin, J ) 1.9, 6.0 Hz, H-5), 2.85 (1H, dt, J ) 3.2, 8.8
Hz, H-3a), 2.60-2.46 (3H, m, H-3b, H-6a, H-9), 2.35 (1H, ddd,
J ) 1.9, 3.3, 12.8 Hz, H-8a), 2.05 (1H, dt, J ) 1.9, 13.0 Hz,
H-6b), 1.94-1.77 (3H, m, H-1a, H-2a, H-8b), 1.67 (1H, m,
H-2b), 1.36 (1H, m, H-1b), 0.91 (3H, d, J ) 6.0 Hz, NCHCH3);
13C NMR (CDCl3) δ 144.1 (C, C-7), 110.0 (CH2, CdCH2), 55.4
(CH, C-9), 50.4 (CH, C-5), 48.5 (CH2, C-3), 40.2 (CH2, C-6),
40.1 (CH2, C-8), 30.4 (CH2, C-1), 21.2 (CH2, C-2), 10.3 (CH3,
NCHCH3); anal. C 79.25%, H 11.41%, N 8.97%, calcd for
1
14: 18% yield; H NMR (CDCl3) δ 3.20 (1H, m, H-9). 3.10
(1H, m, H-5), 2.22 (2H, m, H-2a, H-2b), 2.00 (1H, m, H-1a),
1.72 (1H, d, J ) 12.8 Hz, H-8a), 1.60 (3H, d, J ) 6.5 Hz,
NCHCH3), 1.60-1.40 (3H, m, H-1b, H-6a, H-7), 0.85 (3H, d, J
) 5.8 Hz, CHCH3), 0.85 (1H, m, H-6b), 0.80 (1H, m, H-8b);
13C NMR (CDCl3) δ 175.6 (C, CO), 59.8 (CH, C-9), 52.7 (CH,
C-5), 43.6 (CH2, C-6), 41.5 (CH2, C-8), 32.2 (CH2, C-2), 30.6
(CH, C-7), 25.1 (CH2, C-1), 21.7 (CH3, CHCH3), 19.7 (CH3,
NCHCH3).
C
10H17N, C 79.47%, H 11.26%, N 9.27%.
(5R,9S)-8a : 18% yield; [R]25D -12.0 (c 0.8, CHCl3); 1H NMR
(CDCl3) δ 4.65 (2H, s, CdCH2), 3.24 (1H, dt, J ) 2.3, 8.8 Hz,
H-3a), 2.38 (1H, ddd, J ) 1.6, 1.8, 12.2 Hz, H-8a), 2.18 (1H,
dd, J ) 1.6, 10.4 Hz, H-6a), 2.00-1.60 (8H, m), 1.53-1.40 (1H,
m, H-1a), 1.13 (3H, d, J ) 5.8 Hz, NCHCH3); 13C NMR (CDCl3)
δ 146.2 (C, C-7), 108.2 (CH2, CdCH2), 65.4 (CH, C-9), 58.9 (CH,
C-5), 51.0 (CH2, C-3), 42.7 (CH2, C-6), 40.0 (CH2, C-8), 30.3
(CH2, C-1), 20.9 (CH3, NCHCH3) 20.8 (CH2, C-2).
Refer en ces a n d Notes
(1) Lu¨ning, B.; Leander, K. Acta Chem. Scand. 1965, 19, 1607-1611.
(2) Lu¨ning, B.; Lundin, C.; Acta Chem. Scand. 1967, 21, 2136-2142.
Sonnet, P. E.; Netzel, D. A.; Mendoza, R. J . Heterocycl. Chem. 1979,
16, 1041-1047.
(3) Blomquist, L.; Leander, K.; Lu¨ning, B.; Rosenblom, J . Acta Chem.
Scand. 1972, 26, 3203-3206.
(4) Diederich, M.; Nubbemeyer, U. Synthesis 1999, 286-289. Hsu, R.-
T.; Cheng, L.-M.; Chang, N.-C.; Tai, H.-M. J . Org. Chem. 2002, 67,
5044-5047.
(5S,9S)-7b: [R]25 -9.2 (c 1.9, CHCl3).
D
(5S,9R)-8b: [R]25 +12.9 (c 1.3, CHCl3).
D
5,7-Dim eth ylin d olizid in es. (5R,7R,9R)-9a : [R]25D +7.0 (c
(5) Chalard, P.; Remuson, R.; Gelas-Mialhe, Y.; Gramain, J .-C.; Canet,
I. Tetrahedron Lett. 1999, 40, 1661-1664.
1
0.4, CHCl3); H NMR (CDCl3) δ 3.28 (1H, m, H-5); 2.75 (1H,
(6) Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2, 183-186.
dt, J ) 2.7, 8.6 Hz, H-3a), 2.50 (1H, q, J ) 8.6 Hz, H-3b), 2.40
(1H, m, H-9), 1.80-1.65 (3H, m, H-2a, H-1a, H-8a), 1.65-1.50
NP049902U