L. Rambaud et al. / Tetrahedron: Asymmetry 12 (2001) 1807–1809
1809
Scheme 3. Reagents and conditions: (e) Bis(tricyclohexylphosphine)benzylidine ruthenium(IV) dichloride (Grubb’s catalyst),
toluene, 60°C, 72 h; 30%; (f) H2, Pd/C, MeOH/THF/HCl 6N (4/1/0.25), rt, 20 h; 82%.
conducted with 10% palladium on carbon to complete
the synthesis of (+)-hyacinthacine A2, [h]D +12.5 (c 0.4,
H2O), in 82% yield.17 The configurations of the stereo-
genic centers in this product were confirmed by the
definite nOe effects between C(1)H and C(3)H and
between C(2)H and C(7a)H in the corresponding triac-
etate. Thus, (+)-hyacinthacine A2 was determined to be
(1R,2R,3R,7aR)-1,2-dihydroxy-3-
6. Nash, R. J.; Fellows, L. E.; Dring, J. V.; Fleet, G. W. J.;
Girdhar, A.; Ramsden, N. G.; Peach, J. M.; Hegarty, M.
P.; Scofield, A. M. Phytochemistry 1990, 29, 111–114.
7. (a) Fellows, L.; Nash, R. PCT Int. Appl. WO GB Appl.
89/7,951; Chem. Abstr. 1991, 114, 143777s; (b) Taylor, D.
L.; Nash, R.; Fellows, L. E.; Kang, M. S.; Tyms, A. S.
Antiviral Chem. Chemother. 1992, 3, 273–277.
8. One example of such a cyclization has been reported:
Liotta, L. J.; Ganem, B. Synlett 1990, 503–504.
hydroxymethylpyrrolizidine.
9. For total syntheses of (+)-australine, see: (a) White, J. D.;
Hrnciar, P. J. Org. Chem. 2000, 65, 9129–9142; (b)
Romero, A.; Wong, C.-H. J. Org. Chem. 2000, 65, 8264–
8268; (c) Pearson, W. H.; Hines, J. V. J. Org. Chem.
2000, 65, 5785–5793; (d) Denmark, S. E.; Martinbor-
ough, E. A. J. Am. Chem. Soc. 1999, 121, 3046–3056; (e)
White, J. D.; Hrnciar, P.; Yokochi, A. F. T. J. Am.
Chem. Soc. 1998, 120, 7359–7360; (e) Pearson, W. H.;
Hines, J. V. Tetrahedron Lett. 1991, 32, 5513–5516.
10. For total synthesis of (+)-casuarine, see: Denmark, S. E.;
Hurd, A. R. J. Org. Chem. 2000, 65, 2875–2886.
In conclusion, we have achieved the first synthesis of
(+)-hyacinthacine A2 in only six steps and 11% overall
yield from commercially available 2,3,5-tri-O-benzyl-D-
arabinofuranose. It is noteworthy that very recently,
Yoda et al. reported the synthesis of 7-deoxyalexine
(i.e. 7a-epihyacinthacine A2) from the same starting
material in 26 steps (with an impressive overall yield of
25%).18 Our synthetic strategy is currently being opti-
mized and extended to other pyrrolizidines such as
casuarine and australine.
11. (a) Boschetti, A.; Nicotra, F.; Panza, L.; Russo, G. J.
Org. Chem. 1988, 53, 4181–4185; (b) Alternatively, 1
Acknowledgements
could be obtained in high yield from tri-O-benzyl-D-glu-
cal by dihydroxylation (OsO4, NMO) followed by Wittig
reaction (Ph3P+CH3Br−, nBuLi); see: Charette, A. B.;
Marcoux, J.-P.; Coˆte´, B. Tetrahedron Lett. 1991, 32,
7215–7218; Vidal, T.; Haudrechy, A.; Langlois, Y. Tetra-
hedron Lett. 1999, 40, 5677–5680.
This work was supported by a grant from CNRS. We
are grateful to Drs. B. Perly (CEA) and S. Chierici
(Grenoble University) for 2D NMR experiments. We
thank Professor Asano (Hokuriku University, Japan)
for optical activity measurements and J. Yuan (State
University of New York, Binghamton) for preliminary
experiments.
12. Martin, O. R.; Liu, L.; Yang, F. Tetrahedron Lett. 1996,
37, 1991–1994.
13. For a recent review, see: Roy, R.; Das, S. K. Chem.
Commun. 2000, 519–529.
14. For a review, see: Phillips, A. J.; Abell, A. D. Aldrichim.
Acta 1999, 32, 75–89.
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17. Spectral properties of synthetic (+)-hyacinthacine A2 are
in good agreement with the reported data for the natural
product.5 Selected data: 13C NMR (D2O-TSP) for syn-
thetic hyacinthacine A2: l 27.4; 32.6; 57.7; 65.8; 68.8;
72.0; 80.1; 83.0. {lit.5 13C NMR (D2O-TSP): l 27.3, 32.5,
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same conditions as the natural product gave [h]D +23 (c
0.04, H2O), {lit.5 [h]D +20.1 (c 0.44, H2O)}.
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