5398
S. Ledoux et al. / Tetrahedron Letters 42 (2001) 5397–5399
of 7 prepared by direct bromination of natural
lupinine.14
Direct substitution of the bromine by acetate was
described with a very poor yield,15 but recent condi-
tions using aqueous copper sulfate in DMSO16 were
particularly performing with compound 7. In fact,
optically pure lupinine 317 was finally isolated in 80%
yield. Once more, optical purity was in complete
agreement with literature data.18
In conclusion, chiral cyclic b-amino esters are very
versatile synthons for the synthesis of pyrrolizidine
and quinolizidine alkaloids. After diastereoselective
introduction of an allyl substituent, appropriate chem-
ical transformations can easily lead to bicyclic struc-
tures found in many natural products.
References
Further chemical reduction of the ester function led
selectively to isoretronecanol 29 with excellent yield.
However, due to the possible epimerization a to the
ester function, a reverse reduction of LiAlH4 was per-
formed (addition of 5 at −78°C to a suspension of
LiAlH4 in THF). One more time, [h]2D0=74 (c 0.45,
EtOH) which agrees with the literature.10
1. For pyrrolizidine alkaloids, see: (a) Numata, A.; Ibuka,
T. In The Alkaloids; Brossi, A., Ed.; Academic Press: San
Diego, 1987; Vol. 31, Chapter 6, p. 193; (b) Robins, D. J.
J. Nat. Prod. Rep. 1989, 6, 221; (c) Robins, D. J. J. Nat.
Prod. Rep. 1993, 10, 487; (d) Robins, D. J. J. Nat. Prod.
Rep. 1994, 11, 613.
2. For quinolizidine alkaloids, see: (a) Saito, K.; Murakoshi,
I. In Studies in Natural Products Chemistry 15; Atta-ur-
Rahman, Ed., Chemistry, Biochemistry and Chemotax-
onomy of Lupin Alkaloids in the Leguminosae; Elsevier:
Amsterdam, 1995; p. 519; (b) Michael, J. P. J. Nat. Prod.
Rep. 1997, 14, 613.
3. (a) Bardou, A.; Ce´le´rier, J. P.; Lhommet, G. Tetrahedron
Lett. 1998, 39, 5189–5192; (b) Bardou, A.; Ce´le´rier, J. P.;
Lhommet, G. Tetrahedron Lett. 1997, 38, 8507–8510.
4. (a) Ledoux, S.; Ce´le´rier, J. P.; Lhommet, G. Tetrahedron
Lett. 1999, 40, 9019–9020; (b) Morley, C.; Knight, D. W.;
Share, A. C. Tetrahedron: Asymmetry 1990, 1, 147–150.
5. Noland, W. E.; Sellstedt, J. H. J. Org. Chem. 1966, 31,
345–347.
For the synthesis of quinolizidinic skeleton, a regio-
selective hydroxylation of the double bond of 1 (n=2)
was performed byhydroboration. However, the pres-
ence of a nucleophilic nitrogen in the molecule did
not permit to apply classical conditions (BH3/
DMS) described by Knight et al.4,11 No hydro-
genolysis was possible with this b-amino ester but an
excess of complex BH3/THF led with good yield to
the b-amino diol 6. After debenzylation of 6, a treat-
ment with PBr5 in refluxing benzene as described
Scho¨pf et al.12 led to the cyclized bromo lupinane 7.13
The very good optical purity of this compound was
established by comparison with an analytical sample
6. Spectral data for Chysine B 5: 1H NMR 250 MHz
(CDCl3) l (ppm) 1.21 (t, 3H, J=7 Hz); 1.24–1.28 (m,
1H); 1.72–2.10 (m, 6H); 2.49–2.53 (m, 1H); 2.26–2.27 (m,
1H); 2.85–3.05 (m, 1H); 3.27–3.34 (m, 1H); 3.78–3.84 (m,
1H); 4.13 (d, 2H, J=7 Hz). 13C NMR 62.5 MHz (CDCl3)
l (ppm) 14.1; 26.3; 27.2; 27.9; 46.2; 53.2; 55.3; 61.1; 67.0;
173.3; Rf: 0.20 (MeOH/CHCl3-1/1). [h]2D0 +54 (c 1.25,
EtOH).
7. Sauthar, J. W.; Buckimgham, J. Dictionary of Alkaloids;
Chapman and Hall: London, P-00444, p. 898.
8. Rueger, H.; Benn, M. Heterocycles 1982, 19, 1677–1680.
1
9. Spectral data for isoretronecanol 2: H NMR 250 MHz
(CDCl3) l (ppm) 1.25–1.72 (m, 6H); 2.23–2.27 (m, 1H);
2.31–2.35 (m, 1H); 2.41–2.46 (m, 1H); 2.82–2.86 (m, 1H);
2.96–2.99 (m, 1H); 3.31–3.35 (m, 1H); 3.42–3.45 (m, 2H).
13C NMR 62.5 MHz (CDCl3) l (ppm) 25.9; 26.7; 27.2;
43.0; 54.2; 55.9; 61.0; 69.6. Eb 180°C (0.05 mmHg). [h]D20
+74 (c 0.45, EtOH).
10. Robins, D. J.; Sakdatat, S. J. Chem. Soc., Perkin Trans.
1 1981, 909–913.