2806
L. L. Etchells et al. / Tetrahedron Letters 46 (2005) 2803–2807
OH
HO
CO CH
2 3
HO
CO CH
2 3
H C
33 16
H
C
H C
33 16
33 16
CO CH
2 3
4
3
i)
1
O
O
11'
O
2
5
6
N
N
N
28
29
27
Scheme 6. Reagents and conditions: (i) CDCl3, rt, 10 d, 39%.
3. Ma, D.; Sun, H. Tetrahedron Lett. 2000, 41, 1947–1950.
4. Tsukamoto, S.; Takeuchi, S.; Ishibashi, M.; Kobayashi, J.
J. Org. Chem. 1992, 57, 5255–5260.
5. Kobayashi, J.; Tsukamoto, S.; Takeuchi, S.; Ishibashi, M.
Tetrahedron 1993, 49, 5955–5960.
6. Ishibashi, M.; Takeuchi, S.; Kobayashi, J. Tetrahedron
Lett. 1993, 34, 3749–3750.
7. Shen, Y.-C.; Prakash, C. V. S.; Kuo, Y.-H. J. Nat. Prod.
2001, 64, 324–327.
8. Wells, R. J. Tetrahedron Lett. 1976, 17, 2637–2638.
9. Murayama, T.; Ohizumi, Y.; Nakamura, H.; Sasaki, T.;
Kobayashi, J. Experientia 1989, 45, 898–899.
10. (a) Al-Busafi, S.; Drew, M. G. B.; Sanders, T.; Whitehead,
R. C. Tetrahedron Lett. 1998, 39, 1647–1650; (b) Al-
Busafi, S.; Whitehead, R. C. Tetrahedron Lett. 2000, 41,
3467–3470; (c) Al-Busafi, S.; Doncaster, J. R.; Drew, M.
G. B.; Regan, A. C.; Whitehead, R. C. J. Chem. Soc.,
Perkin Trans. 1 2002, 476–484; (d) Doncaster, J. R.; Ryan,
H.; Whitehead, R. C. Synlett 2003, 651–654.
11. Huang-Minlon J. Am. Chem. Soc. 1946, 68, 2487–2488;
Huang-Minlon J. Am. Chem. Soc. 1949, 71, 3301–3303.
12. Levisalles, J. Bull. Soc. Chim. Fr. 1957, 997.
13. Williams, P. D.; LeGoff, E. J. Org. Chem. 1981, 46, 4143–
4147.
Thus imine 27, contaminated with <5% phenethylamine
(21), was exposed at rt to 110 in CDCl3 (Scheme 6). After
10 d, analysis by H NMR indicated substantial forma-
tion of plakoridine analogue 28 and a small quantity of
diastereoisomer 29. Purification by flash chromatogra-
phy did not allow separation of the isomers and pro-
vided 28 contaminated with <5% of 29. The relative
stereochemistry of 28 was assigned by analogy with that
of 24 and by the similar magnitude of the vicinal cou-
1
pling
constant
between
C(3)H
and
C(4)H
(J3,4 = 6.4 Hz). The observation of a strong NOE be-
tween C(4)H and the ortho hydrogens of the aromatic
substituent at C5and a weak NOE between C(3) H
and C(5)H are also in accord with the proposed
structure.
In summary, we have prepared two unnatural analogues
of the plakoridines in five linear steps from the methyl
ester of 2-furan acetic acid (15), using an approach mod-
eled on a plausible and apparently unprecedented bio-
synthetic pathway. Preliminary studies indicate that
the relative stereochemistry of the natural products is
under thermodynamic control. We consider that the
yield of the key biomimetic transformation (ꢁ40%) is
reasonable given the complexity of the cascade
sequence. Investigations are now underway to further
delineate the scope of the synthetic route and to investi-
gate the factors controlling the efficiency of the final
transformation.
14. MacLeod, J. K.; Bott, G.; Cable, J. Aust. J. Chem. 1977,
30, 2561–2564.
15. Piancatelli, G.; Scettri, A.; DÕAuria, M. Tetrahedron 1980,
36, 661–663.
16. Jurczak, J.; Pikul, S. Tetrahedron Lett. 1985, 26, 3039–
3040.
17. Simion, A.; Simion, C.; Kanda, T.; Nagashima, S.;
Mitoma, Y.; Yamada, T.; Mimura, K.; Tashiro, M. J.
Chem. Soc., Perkin Trans. 1 2001, 2071–2078.
18. Spectroscopic data for compound 24: mmax (film)/cmꢀ1
3460w (O–H), 2923s and 2853s (C–H), 1740s (C@O),
1624m (C@O), 1534s; dH (500 MHz; CDCl3) 0.81 and 0.82
(2 · 3H, 2 · t, J 7.0, C(23)H3 and C(27)H3), 1.13–1.28
(26H, m, C(10)H2–C(22)H2), 1.48–1.58 (3H, m, C(9)H2
and one of C(26)H2), 1.72–1.81 (1H, m, one of C(26)H2),
2.25–2.35 (2H, m, C(8)H2), 2.75(1H, ddd, J 15.0, 9.5, 5.5,
one of C(29)H2), 2.84 (1H, ꢁt, J 6.0, C(4)H), 2.81–2.88
(1H, m, one of C(29)H2), 3.25(1H, ddd, J 15.0, 9.5, 6.5,
one of C(28)H2), 3.41 (1H, ddd, J 15.0, 9.0, 5.5, one of
C(28)H2), 3.64–3.67 (1H, m, C(5)H), 3.68 (3H, s, CO2
CH3), 5.04 (1H, s, C(6)H), 5.14 (1H, d, J 5.5, C(3)H), 7.12
(2H, d, J 7.5, C(31/35)H), 7.19 (1H, t, J 7.5, C(33)H), 7.26
(2H, t, J 7.5, C(32/34)H); dC (100 MHz; CDCl3) 8.33 and
14.10 (C(23)H3 and C(27)H3), 22.67, 25.44, 26.25, 29.34,
29.55, 29.68 and 31.91 (C(9)H2–C(22)H2 and C(26)H2,
many coincident), 32.01 (C(29)H2), 43.49 (C(8)H2), 45.84
(C(28)H2), 51.56 (C(4)H), 52.50 (CO2 CH3), 66.04
(C(5)H), 75.72 (C(3)H), 90.28 (C(6)H), 126.91 (C(33)H),
128.58 and 128.81 (C(31/35)H and C(32/34)H), 137.94
(C(30)), 165.79 (C(2)), 172.73 (CO2CH3), 199.83
(C(7)@O); m/z (CI/NH3) 542 (MH+, 100%), 526 (15),
274 (40), 162 (32), 104 (40); (Found 542.4201: C34H56NO4
(MH+) requires 542.4204).
Acknowledgements
We acknowledge, with thanks, the EPSRC for funding
(L.L.E. and A.S.). We are particularly grateful to Pro-
fessor Ma of the Shanghai Institute of Organic Chemis-
try and Professor Kobayashi of Hokkaido University
1
for the generous provision of the H NMR spectra of
(ꢀ)-plakoridine A and natural plakoridine A, respec-
tively. We also thank Professor Gareth Morris of The
University of Manchester for invaluable advice concern-
ing the NMR analysis of compounds 24 and 25 and
Miss Hazel Ryan for carrying out investigations into
the preparation of 20.
References and notes
1. Takeuchi, S.; Ishibashi, M.; Kobayashi, J. J. Org. Chem.
1994, 59, 3712–3713.
2. Takeuchi, S.; Kikuchi, T.; Tsukamoto, S.; Ishibashi, M.;
Kobayashi, J. Tetrahedron 1995, 51, 5979–5986.