LETTER
Chem. 2002, 67, 4630. (l) Lindsay, K. B.; Pyne, S. G. J.
Efficient Synthesis of Trihydroxy Quinolizidine Alkaloids
1551
reaction mixture was refluxed under nitrogen for 18 h.
Org. Chem. 2002, 67, 7774. (m) Buschmann, N.; Rückert,
A.; Blechert, S. J. Org. Chem. 2002, 67, 4325. (n) Lee, H.
K.; Chun, J. S.; Pak, C. S. J. Org. Chem. 2003, 68, 2471.
(o) Verhelst, S. H. L.; Martinez, B. P.; Timmer, S. M.;
Lodder, G.; Van der Marel, G. A.; Overkleeft, H. S.; van
Boom, J. H. J. Org. Chem. 2003, 68, 9598.
Removal of solvent under vacuum afforded a thick oil that
on purification by column chromatography using EtOAc–
n-hexane (5:95) afforded corresponding D3-piperidine 6a,b.
General Procedure for the Reductive Aminocyclization:
A solution of 7a,7b (0.100 g, 0.26 mmol) in TFA–H2O (3:2,
2 mL) was stirred at 25 °C for 2 h. TFA was co-evaporated
with benzene to furnish a thick liquid, which was directly
used in the next reaction. To a solution of the above product
in MeOH (5 mL) was added 10% Pd/C (0.01 g) and the
solution was hydrogenated at 80 psi for 16 h. The solution
was filtered through celite and the filtrate concentrated to get
a sticky solid, which was purified by column
(3) (a) Grandnig, G.; Berger, A.; Grassberger, V.; Stuetz, A.
Tetrahedron Lett. 1991, 32, 4849. (b) Rassu, G.; Casiraghi,
G.; Pinna, L.; Spanu, P.; Ulgheri, F.; Cornia, M.; Zanardi, F.
Tetrahedron 1993, 49, 6627. (c) Herzegh, P.; Kovacs, I.;
Szilagyi, L.; Sztaricskai, F.; Bericibar, A.; Riche, C.;
Chiaroni, A.; Olesker, A.; Lukacs, G. Tetrahedron 1995, 51,
2969. (d) Carretero, J. C.; Arrayas, R. G.; De Garcia, I. S.
Tetrahedron Lett. 1997, 38, 8537. (e) Iminosugars as
Glycosidase Inhibitors; Stuetz, A. E., Ed.; Wiley-VCH:
Weinheim, 1999. (f) Schaller, C.; Vogel, P. Synlett 1999,
1219.
chromatography (MeOH–CHCl3 = 5:95) to give 1a,b.
(9) All new compounds have been characterized by 1H NMR,
13C NMR, and elemental analysis. Selected procedures and
data for 3-O-benzyl-1,2-O-isopropylidene-5,6,7,8-tetra-
deoxy-5-(N-benzyl-N-hydroxyamino)-a-D-gluco-7-eno-
octo-1,4-furanose (3a): thick liquid; 80%; Rf = 0.52
(EtOAc–hexane = 3:7); [a]D = –30.0 (c 2.40, CHCl3). IR
(neat): 3510–3160 (br), 1639 cm–1. 1H NMR (300 MHz,
CDCl3): d = 1.26 (s, 3 H), 1.44 (s, 3 H), 2.49–2.69 (m, 2 H),
3.41 (ddd, J = 8.3, 7.8, 4.8 Hz, 1 H), 3.76 (d, J = 13.6 Hz, 1
H), 3.94 (d, J = 13.6 Hz, 1 H), 4.01 (d, J = 3.0 Hz, 1 H), 4.37
(dd, J = 8.3, 3.0 Hz, 1 H), 4.40–4.45 (br s, exchanges with
D2O, 1 H), 4.50 (d, J = 11.7 Hz, 1 H), 4.54 (d, J = 3.9 Hz, 1
H), 4.63 (d, J = 11.7 Hz, 1 H), 4.98 (dd, J = 11.1, 1.6 Hz, 1
H), 5.10 (dd, J = 17.0, 1.6 Hz, 1 H), 5.87 (d, J = 3.9 Hz, 1
H), 5.92–6.10 (m, 1 H), 7.12–7.28 (m, 10 H). 13C NMR (75
MHz, CDCl3): d = 26.2, 26.7, 31.4, 60.8, 63.4, 72.0, 79.6,
81.9, 82.5, 104.5, 111.3, 115.6, 127.1, 127.5, 127.6, 128.2,
128.4, 129.1, 137.6, 137.7, 138.3. Anal. Calcd for
(4) (a) Michael, J. Nat. Prod. Rep. 1999, 16, 675. (b) Michael,
J. Nat. Prod. Rep. 2000, 17, 579. (c) Michael, J. Nat. Prod.
Rep. 2003, 20, 458.
(5) (a) Dhavale, D.; Desai, V.; Sindkhedkar, M.; Mali, R.;
Castellari, C.; Trombini, C. Tetrahedron: Asymmetry 1997,
1475. (b) Dhavale, D.; Saha, N.; Desai, V. J. Org. Chem.
1997, 62, 7482. (c) Dhavale, D.; Saha, N.; Desai, V. J. Org.
Chem. 1999, 64, 1715. (d) Dhavale, D.; Saha, N.; Desai, V.
J. Chem. Soc., Chem. Commun. 1999, 1719. (e) Saha, N.;
Desai, V.; Dhavale, D. Tetrahedron 2001, 39. (f) Patil, N.;
Tilekar, J.; Dhavale, D. J. Org. Chem. 2001, 66, 1065.
(g) Patil, N.; Tilekar, J.; Dhavale, D. Tetrahedron Lett. 2001,
42, 747. (h) Dhavale, D.; Patil, N.; John, S.; Sabharwal, S.
Bioorg. Med. Chem. 2002, 10, 2155. (i) Dhavale, D.; Saha,
N.; Desai, V.; Tilekar, J. Arkivoc 2002, 91. (j) Patil, N.;
Tilekar, J.; Jadhav, H.; Dhavale, D. Tetrahedron 2003, 59,
1873.
(6) (a) Liu, P.; Rogers, R.; Kang, M.; Sankara, P. Tetrahedron
Lett. 1991, 32, 5853. (b) Pearson, W.; Hembre, E.
Tetrahedron Lett. 1993, 8221. (c) Herczegh, P.; Kovacs, I.;
Szilagyi, L.; Sztaricskai, F. Tetrahedron 1995, 51, 2969.
(d) Carretero, J.; Arrayas, R.; Gracia, I. Tetrahedron Lett.
1997, 38, 8537. (e) Pearson, W.; Hembre, E. J. Org. Chem.
1996, 61, 5537. (f) Hamana, H.; Ikota, N.; Ganem, B. J.
Org. Chem. 1987, 52, 5492. (g) Pandit, U. K.; Overkleeft,
H.; Borer, B. C.; Bieraugel, H. Eur. J. Org. Chem. 1999,
959. (h) Schaller, C.; Vogel, P. Helv. Chim. Acta 2000, 193.
(i) Gebarowski, P.; Sas, W. Chem. Commun. 2001, 915.
(7) (a) It is known that for a given C5-epimeric pair, derived
from the D-gluco-furanose, the J4,5 in the L-ido isomer
(threo-relationship) is consistently larger than that of the
corresponding D-gluco isomer (erythro-relationship). In
addition, the chemical shift of H-3 in L-ido isomer is upfield
as compared to D-gluco isomer. The higher value of J4,5
observed in the diastereomer 3b (9.5 Hz) as compared to 3a
(8.3 Hz) indicated the L-ido configuration for 3b and the D-
gluco configuration for 3a. This fact was further supported
by comparison of the chemical shift of H-3 in both the
isomers. In 3b H-3 appeared upfield at d = 3.84 ppm as
compared to 3a at d = 4.01 ppm, further supporting the D-
gluco- and L-ido configuration at C5 to 3a and 3b,
respectively. Thus, the absolute configurations at C-5 in 3a
and 3b were assigned as (5R) and (5S), respectively.
(b) See: Cornia, M.; Casiraghi, G. Tetrahedron 1989, 45,
2869.
C25H31NO5: C, 70.57; H, 7.34. Found: C, 70.51; H, 7.30.
3-O-Benzyl-1,2-O-isopropylidene-5,6,7,8-tetra-deoxy-5-
(N-benzyl-N-hydroxyamino)-b-L-ido-7-eno-octo-1,4-
furanose (3b): thick liquid; 13%; Rf = 0.44 (EtOAc–
hexane = 3:7); [a]D = –48.0 (c 0.25, CHCl3). IR (neat):
3530–3150 (br), 1639 cm–1. 1H NMR (300 MHz, CDCl3):
d = 1.27 (s, 3 H), 1.46 (s, 3 H), 1.91–2.09 (m, 1 H), 2.21–2.35
(m, 1 H), 3.38 (ddd, J = 9.5, 8.1, 4.3 Hz, 1 H), 3.84 (d,
J = 3.0 Hz, 1 H), 3.92 (d, J = 13.9 Hz, 1 H), 4.09 (d, J = 13.9
Hz, 1 H), 4.39 (d, J = 11.6 Hz, 1 H), 4.44 (dd, J = 9.5, 3.0
Hz, 1 H), 4.57 (d, J = 3.8 Hz, 1 H), 4.61 (d, J = 11.6 Hz, 1
H), 4.84–4.92 (m, 2 H), 4.93–4.96 (br s, exchanges with
D2O, 1 H), 5.83–6.05 (m, 1 H), 5.93 (d, J = 3.8 Hz, 1 H),
7.10–7.38 (m, 10 H). 13C NMR (75 MHz, CDCl3): d = 26.5,
26.8, 34.3, 49.4, 57.3, 72.0, 81.3, 81.9, 83.5, 104.9, 111.3,
115.0, 126.2, 127.4, 127.5, 127.7, 128.2, 128.4, 137.9,
138.2, 141.5. Anal. Calcd for C25H31NO5: C, 70.57; H, 7.34.
Found: C, 70.29; H, 7.59.
3-O-Benzyl-5,6-dideoxy-1,2-O-isopropylidene-5-(N-
benzyl-N-propenylamino)-a-D-gluco-7-eno-octo-1,4-
furanose (5a): thick liquid; 71%; Rf = 0.65 (EtOAc–hex-
ane = 2:8); [a]D = –36.4 (c 0.44, CHCl3). IR (neat): 1639,
1605 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.30 (s, 3 H),
1.46 (s, 3 H), 2.48 (br t, J = 7.2 Hz, 2 H), 3.12 (dd, J = 14.1,
6.6 Hz, 1 H), 3.22 (dd, J = 14.1, 6.3 Hz, 1 H), 3.34 (q, J = 7.2
Hz, 1 H), 3.73 (ABq, J = 14.4 Hz, 2 H), 3.95 (d, J = 3.0 Hz,
1 H), 4.22 (dd, J = 7.2, 3.0 Hz, 1 H), 4.48 (d, J = 11.7 Hz,
1 H), 4.53 (d, J = 3.6 Hz, 1 H), 4.63 (d, J = 11.7 Hz, 1 H),
4.87–5.18 (m, 4 H), 5.63–5.80 (m, 1 H), 5.89 (d, J = 3.6 Hz,
1 H), 5.92–6.08 (m, 1 H), 7.16–7.22 (m, 10 H). 13C NMR (75
MHz, CDCl3): d = 26.2, 26.8, 32.9, 54.5, 54.7, 57.3, 71.8,
79.9, 81.6, 82.7, 104.7, 111.4, 115.4, 116.6, 126.7, 127.6,
127.7, 128.1, 128.3, 128.5, 137.2, 137.6, 138.3, 140.5. Anal.
Calcd for C28H35NO4: C, 74.80; H, 7.85. Found: C, 74.65; H,
7.70.
(8) General Procedure for the Ring-Closing Metathesis: To a
solution of 5a,b (0.180 g, 0.4 mmol) in dry benzene (15 mL)
at 25 °C was added benzylidene-bis-tricyclohexyl-
phosphine-dichlororuthenium (0.006 g, 5% mol) and the
Synlett 2004, No. 9, 1549–1552 © Thieme Stuttgart · New York