LETTER
Synthesis of a Polyhydroxyquinolizidine bearing a Polyhydroxylated Carbon Side-Chain
1221
B. Tetrahedron: Asymmetry 1991, 2, 75; Corey, E. J.; Loh, J.-
L. Tetrahedron Lett. 1993, 34, 3979; Forster, A.; Mosimann,
H.; Renaud, P.; Vogel, P. Tetrahedron: Asymmetry 1999, 10,
567.
uct. Debenzylation was expected to generate 24. The pri-
mary amine of 24 equilibrates with imines resulting from
its reaction with the aldose moieties, imines that are re-
duced into the corresponding piperidines under our hydro-
genation conditions. A possible piperidine intermediate is
25 which undergoes formation of an intermediate imini-
um salt with the second aldose moiety that is reduced into
2. This polyol was fully characterized as its octaacetate
(+)-26 obtained in 40% yield (based on (-)-21) on treating
crude 2 with Ac2O/pyridine and 4-dimethylaminopyridine
as catalyst (25°C, 15 h).29
(7) Jäger, V.; Müller, I. Tetrahedron 1985, 41, 3519; see also:
Jäger, V.; Müller, R.; Leibold, T.; Hein, M.; Schwarz, M.;
Fengler, M.; Jaroskova, L.; Pätzel, M.; Le Roy, P.-Y. Bull.
Chem. Soc. Belg. 1994, 103, 491.
(8) Schaller, C.; Vogel, P.; Jäger, V. Carbohydr. Res 1998, 314,
25.
(9) Black, K. A.; Vogel, P. J. Org. Chem. 1986, 57, 5341.
(10) Data for (+)-6: m.p. 111-112 °C; [a]25D +50 (c=1.0, CHCl3);
1H-NMR (400 MHz, CDCl3) dH: 7.61-7-65 (m, 2H), 7.35-7.32
(m, 3H), 5.77 (d, 3J=3.6, H-4a''), 5.68 (d, 3J=6.4, H-3a''), 4.96
(d, 3J=6.4, H-7b''), 4.84 (dd, 3J=8.3, 2.6, H-1'), 4.78-4.76 (m,
H-7a'', H-4), 4.54 (d, 3J=5.6, H-1), 4.29 (ddd, 3J=5.6, 2.8,
4J=1.0, H-6), 3.65 (d, 3J=2.8, H-5), 3.35 (d, 3J=2.6, HO-
C(1')), 2.78 (d, 3J=8.3, H-3), 1.50, 1.37 (2s, 2 Me).
(11) Data for (+)-7: [a]25D +28 (c=1.1, CHCl3).
This work demonstrates that the cross-aldolization of al-
dehydes such as (+)-5 with 7-oxabicyclo[2.2.1]hep-
tanones can be highly stereoselective, thus allowing one
to construct complicated long-chain amino-deoxysugars
via the stereoselective hydride reductions of the isoxazo-
lines so-obtained. Deprotection under hydrogenation con-
ditions converts these systems into quinolizidines. The
first example (2) of a 8-(1',2',3'-trihydroxypropyl)-2H-
quinolizine-1,2,3,7,9-pentol has been reached by this
method. Further efforts should make possible the obten-
tion of stereomers of 2 and of unprotected long-chain ami-
no-deoxycarbohydrates and analogues.
(12) Data for (-)-8: [a]25D -10 (c=0.43, CHCl3).
(13) Data for 9: 1H-NMR (400 MHz, CDCl3) dH: 7.59-7.57 (m,
2H), 7.34-7.31 (m, 3H), 5.70 (d, 3J=3.5, H-4a'), 5.51 (d,
3J=6.4, H-3a'), 4.83 (d, 3J=6.4, H-7b'), 4.78 (dd, 3J=4.2, 3.8,
H-8a), 4.76 (d, 3J=3.5, H-7a'), 4.49-4.47 (m, H-4, H-8), 4.30
(s, H-5), 4.15 (dd, 3J=5.3, 3.5, H-7), 3.51 (d, 3J=5.3, H-6),
2.23 (dd, 3J=10.8, 3.3, H-4a), 1.49, 1.37 (2s, 2 Me), 1.05 (s, 2
t-Bu); 13C-NMR (100.6 MHz, CDCl3) dC: 158.6 (s), 134.0 (d,
2C), 133.9 (s), 129.2 (2d), 127.8, 113.9 (s), 106.1, 87.1, 86.8,
86.5, 84.6, 79.4, 77.1, 68.6, 60.4, 56.6, 51.5 (11d), 27.7, 27.3,
27.1, 26.8 (4q), 24.3, 20.8 (2s).
Acknowledgement
(14) All new compounds presented here gave satisfactory
elemental analyses.
We thank the Swiss National Science Foundation (Bern) and the
Fonds Herbette (Lausanne) for financial support.
(15) Gagnaire, D.; Payo-Subiza, E. Bull. Chem. Soc. Fr. 1963,
2627; Nelson, W. L.; Allen, D. R. J. Heterocycl. Chem. 1972,
9, 561; Kienzle, F. Helv. Chim. Acta 1975, 58, 1180.
(16) Zimmerman, H. E.; Traxler, M. D. J. Am. Chem. Soc. 1957,
79, 1920; see also: Kleschick, W. A.; Buse, C. T.; Heathcock,
C. H. Ibid. 1977, 99, 247; Fellmann, P.; Dubois, J. E.
Tetrahedron 1978, 34, 1349; Evans, D. A.; Vogel, E.; Nelson,
J. V. J. Am. Chem. Soc. 1979, 101, 6120; Heathcock, C. H.;
Buse, C. T.; Kleschick, W. A.; Pirrung, M. C.; Sohn, J. E.;
Rampe, J. J. Org. Chem. 1980, 45, 1066; Seebach, D.; Prelog,
V. Angew. Chem., Int. Ed. Engl. 1982, 21, 654.
References and Notes
(1) Tyler, P. C.; Winchester, B. G. in "Iminosugars as
Glycosidase Inhibitors", Stütz, A. E., Ed., Wiley-VCH,
Weinheim, 1999, Chapter 7, p. 125-156; Ekhart, C. E.;
Fechter, M. H.; Hadwiger, P.; Mlaker, E.; Stütz, A. E.; Tauss,
A.; Wrodnigg, T. M. Ibid. 1999, p. 253-390.
(2) Hamana, H.; Ikota, N.; Ganem, B. J. Org. Chem. 1987, 52,
5492; Liu, P. S. Ibid. 1987, 52, 4717; Gradnig, G.; Berger, A.;
Grassberger, V.; Stütz, A. E.; Legler, G. Ibid. 1991, 32, 4889;
Dax, K.; Fechter, M.; Gradnig, G.; Grassberger, V.;
Illaszewicz, C.; Ungerank, M.; Stütz, A. E. Carbohydr. Res
1991, 217, 59; Rassu, G.; Casiraghi, G.; Pinna, L.; Spanu, P.;
Ulgheri, F.; Cornia, M.; Zanardi, F. Tetrahedron 1993, 49,
6627; Pearson, W. H.; Hembre, E. J. Tetrahedron Lett. 1993,
34, 8221; Pearson, W. H.; Hembre, E. J. J. Org. Chem. 1996,
61, 5537; Herczegh, P.; Kovacs, I.; Szilagyi, L.; Sztaricskai,
F.; Bericibar, A.; Riche, C.; Chiaroni, A.; Olesker, A.; Lukacs,
G. Tetrahedron 1995, 51, 2969; Carretero, J. C.; Arrayas, R.
G.; De Gracia, I. S. Tetrahedron Lett. 1997, 38, 8537;
Overkleeft, H. S.; Bruggeman, P.; Pandit, U. K. Tetrahedron
Lett. 1998, 39, 3869.
(3) Liu, P. S.; Rogers, R. S.; Kang, M. S.; Sunkara, P. S.
Tetrahedron Lett. 1991, 32, 5853.
(4) Kraehenbuehl, K.; Picasso, S.; Vogel, P. Helv. Chim. Acta
1998, 81, 1439.
(5) Chen, Y.; Vogel, P. J. Org. Chem. 1994, 59, 2487; Emery, F.;
Vogel, P. Ibid. 1995, 60, 5843; Baudat, A.; Vogel, P. Ibid.
1997, 62, 6252.
(6) a) Vieira, E.; Vogel, P. Helv. Chim. Acta 1983, 66, 1865; b)
Reymond, J.-L.; Vogel, P. Tetrahedron: Asymmetry 1990, 1,
729; c) Vogel, P.; Fattori, D.; Gasparini, F.; Le Drian, C.
Synlett 1990, 173; d) see also: Saf, R.; Faber, K.; Penn, G.;
Griengl, H. Tetrahedron 1988, 44, 389; Ronan, B.; Kagan, H.
(17) Data for (+)-12: colorless oil; [a]25D = +129 (c=1.1, CHCl3);
UV (MeCN) lmax: 209 nm (e=7000); 1H-NMR (400 MHz,
CDCl3) dH: 6.37 (d, 3J=2.2, H-5), 5.87 (d, 3J=3.6, H-4a''), 5.44
(d, 3J=5.8, H-3a''), 4.97 (d, 3J=2.2, H-4), 4.92 (d, 3J=6.5, H-
1'), 4.84 (d, 3J=5.8, H-7b''), 4.82 (d, 3J=3.6, H-7a''), 4.70-4.68
(m, H-1), 4.69, 4.66 (AB, 2J=6.7, CH2(MOM)), 4.17 (dd,
3J=4.4, 2.4, H-2), 3.39 (s, MeO), 2.02 (dd, 3J=6.5, 2.4, H-3),
1.49, 1.36 (2s, 2 Me), 0.92 (s, t-Bu), 0.11, 0.10 (2s, Me2Si).
(18) Data for (+)-14: mp 55-56 °C, [a]25D +13 (c=1.0, CHCl3).
(19) Arvai, G.; Fattori, D.; Vogel, P. Tetrahedron 1992, 48, 10621.
(20) Data for (+)-15: mp 67-68 °C, [a]25D +18 (c=1.0, CHCl3); IR
(KBr) n: 2930, 1770, 1575, 1390, 1375, 1205, 1190, 1105,
1060, 1010, 840 cm-1; 1H-NMR (400 MHz, CDCl3) dH: 7.83,
7.73 (2d, 3J=8.8, 4H), 5.82 (d, 3J=3.5, H-1), 5.79 (d, 3J=3.5,
H-4a''), 5.56 (d, 3J=6.7, H-3a''), 4.95 (d, 3J=6.7, H-7b''), 4.78
(d, 3J=5.7, H-1'), 4.74 (d, 3J=3.5, H-7a''), 4.73 (s, H-4), 4.64,
4.50 (AB, 2J=7.0, CH2(MOM)), 4.55 (br. s, H-5), 4.19 (dd,
3J=4.5, 3.5, H-7), 3.32 (s, MeO), 2.36 (ddd, 3J=5.7, 4.5, 1.9,
H-6), 1.44, 1.32 (2s, 2 Me), 0.84 (s, t-Bu), 0.06, 0.05 (2s,
Me2Si).
(21) Data for (+)-16: oil, [a]25D +64 (c=0.36, CHCl3); 1H-NMR
(400 MHz, CDCl3): 3J(H-4,H-3) = 3J(H-4,H-5) @ 0, 3J(H-1,H-
2) = 2.3. Data for (+)-17: oil, [a]25D +75 (c=0.25, CHCl3);
3J(H-3,H-4) @ 0, 3J(H-4,H-5) = 4, 3J(H-1,H-2) = 2.0.
Synlett 1999, No. 8, 1219–1222 ISSN 0936-5214 © Thieme Stuttgart · New York