S. M. Allin et al. / Tetrahedron Letters 45 (2004) 5493–5496
5495
CHO
MeO
MeO
MeO
MeO
MeO
(ii)
(i)
N
N
N
6
O
O
O
+
MeO
(iii)
O
O
O
8
9
10
[α]D = - 36.9 (c = 1.16, CHCl3)
MeO
MeO
(iv)
N
O
O
O
[α]D = - 26.1 (c = 1.15, CHCl3)
11,
Scheme 3. Reagents and conditions: (i) Dess–Martin periodinane, DCM; (ii) Rh(PPh3)2(CO)Cl, dppp, mesitylene, D, 4 days; (iii) H2/10% Pd–C,
EtOH; (iv) ethylene glycol, pTSA (cat.), toluene, D.
sequence was completed by catalytic hydrogenation of
the crude mixture from the previous step to furnish the
amidoketone 10 in 79% yield.
cyclisation methodology. Our approach allows a facile
and highly stereoselective formal asymmetric synthesis
of both enantiomers of the alkaloid 3-demethoxyery-
thratidinone.
The formal asymmetric synthesis of (+)-demethoxyery-
thratidinone, the natural enantiomer, simply required
re-protection of the ketone functional group using eth-
ylene glycol as shown in Scheme 3. Compound 11 has
been converted by others to the natural product albeit in
racemic form by a four-step sequence.4
Acknowledgements
Loughborough University, Biofocus Ltd (joint stu-
dentship to G.B.S) and GlaxoSmithKline Pharmaceu-
ticals (joint studentship to S.L.J).
MeO
MeO
References and notes
1. Tanaka, H.; Tanaka, T.; Etoh, H.; Goto, S.; Terada, Y.
Heterocycles 1999, 51, 2759–2764; Dyke, S. F.; Quessy,
S. N. The Alkaloids ; Rodrigo, R. G. A. Academic Press:
New York, 1981; Vol. 18.
MeO
O
O
N
O
N
O
MeO
O
2. (a) Padwa, A.; Hennig, R.; Kappe, C. O.; Reger, T. S.
J. Org. Chem. 1998, 63, 1144–1155, and references cited
therein; (b) Rigby, J. H.; Deur, C.; Heeg, M. J. Tetrahedron
Lett. 1999, 40, 6887–6890; (c) Rigby, J. H.; Hughes, R. C.;
Heeg, M. J. J. Am. Chem. Soc. 1995, 117, 7834–7835; (d)
Suda, Y. T.; Hosai, S.; Ishida, K.; Sangai, M. Chem.
Pharm. Bull. 1994, 42, 204–213; (e) Lete, E.; Egiarte, A.;
Sotomayor, N.; Vicente, T.; Villa, M.-J. Synlett 1993, 41–
42; (f) Manteca, I.; Sotomayor, N.; Villa, M.-J.; Lete, E.
Tetrahedron Lett. 1996, 37, 7841–7844; (g) Lee, Y. S.;
Kang, D. W.; Lee, S. J.; Park, H. J. Org. Chem. 1995, 60,
7149–7152; (h) Lee, Y. S.; Kang, D. W.; Lee, S. J.; Park, H.
Synth. Commun. 1995, 25, 1947–1956; (i) Lee, J. Y.; Lee, Y.
S.; Chung, B. Y.; Park, H. Tetrahedron 1997, 53, 2449–
2458; (j) Katritzky, A. R.; Mehta, S.; He, H.-Y. J. Org.
Chem. 2001, 66, 148–152; (k) Garcia, E.; Arrasate, S.;
Ardeo, A.; Lete, E.; Sotomayor, N. Tetrahedron Lett. 2001,
42, 1511–1513.
O
12
13
[α]D = + 39.6 (c = 1.13, CHCl3)
[α]D = - 55.7 (c = 1.13 , CHCl3)
MeO
MeO
N
O
O
O
14
[α]D = + 21.7 (c = 1.33, CHCl3)
The formal asymmetric synthesis of the unnatural
enantiomer followed an identical synthetic route,
beginning however with the enantiomeric form of the
original amino acid substrate to access the required lac-
tam substrate 12, which had the opposite optical rotation
value to that obtained for lactam 5. Intermediate 13 gave
an optical rotation of +39.6, compared to )36.9 for
compound 10. The enantio-target 14, gave an optical
rotation of +21.7, compared to )26.1 for compound 11.
3. Barton, D. H. R.; Gunatilaka, A. A. L.; Letcher, R. M.;
Lobo, A. M. F. T.; Widdowson, D. A. J. Chem. Soc.,
Perkin Trans. 1 1973, 874–880.
4. Tsuda, Y.; Nakai, A.; Ito, K.; Suzuki, F.; Haruna, M.
Heterocycles 1984, 22, 1817–1820.
5. Hosoi, S.; Ishida, K.; Tsuda, Y. Chem. Pharm. Bull. 1992,
40, 3115–3117.
To summarise, we report the first synthetic application
of our recently developed asymmetric N-acyliminium
6. (a) Allin, S. M.; James, S. L.; Martin, W. P.; Smith, T. A. D. J.
Org. Chem. 2002, 67, 9464–9467; (b) Allin, S. M.; Thomas,