1
65 ЊC for 18 h. After being cooled to room temperature it was
partitioned between diethyl ether (200 mL) and brine (200 mL).
The aqueous phase was re-extracted with diethyl ether (2 × 150
mL) and the combined organic extracts were washed with water
(3 × 150 mL), dried (MgSO4) and filtered. The solvent was
removed from the filtrate at reduced pressure to give the crude
product that was purified by column chromatography. Gradient
0.033 mmol, 59%) as an oil; [α]2D2 ϩ9.1 (c 0.44, CDCl3); H
NMR (CDCl3) δ Ϫ0.09 (6 H, s), 0.00 (6 H, s), 0.78 (18 H, s),
2.65–2.70 (2 H, m), 3.60–3.80 (4 H, m), 3.86–3.89 (2 H, m),
4.35–4.55 (4 H, m), 7.15–7.30 (15 H, m, Ar); 13C NMR.
(CDCl3) δ Ϫ4.3 (t), Ϫ4.2 (t), 18.4 (s), 26.3 (q), 52.3 (t), 63.0 (t),
71.4 (t), 78.6 (d), 82.0 (d), 127.4 (d), 127.6 (d), 127.8 (d), 128.5
(d), 129.6 (d), 139.4 (s); m/z (FAB) 662.4046 [(M ϩ H)ϩ,
C39H60NO4Si2 requires 662.4061], 662 (30%), 171 (10), 91 (100),
73 (50).
elution with hexanes–CH2Cl2 (2.3 : 1
1.5 : 1
1 : 1) afforded
compound 17 (96 mg, 0.13 mmol, 60%) as an oil; [α]2D2 Ϫ27.5
(c 1.92, CDCl3); m/z (FAB) 797.3919 [(M ϩ H)ϩ, C46H61O8Si2
requires 797.3905], 797 (1%), 181 (10), 106 (95), 91 (100), 73
(15). NMR data are given in Table 1.
Acknowledgements
The authors thank the Foundation for Research, Science and
Technology for financial support (Science and Technology
Post-Doctoral Fellowship, contract # C08821 to G. F. P. and
Public Good Science Fund, contract # C08811-D, to A. F.) and
Dr Richard Furneaux for his role as team leader. Prof Robin
Ferrier assisted with the preparation of the manuscript.
2,5-Di-O-benzyl-3,4-bis-O-(tert-butyldimethylsilyl)-D-chiro-
inositol (18)
NaOMe (ca. 0.1–0.2 mL, 30% in MeOH) was added to a stirred
mixture of compound 17 (94 mg, 0.12 mmol) in MeOH (10 mL)
under argon such that the pH was maintained at ca. 12. After
stirring of the mixture at room temperature for 18 h, Amberlite
IR-50(H) was added to neutralise and the mixture was stirred
for 15 min. The reaction mixture was filtered and the solvent
was removed at reduced pressure to give the crude product that
was purified by column chromatography. Elution with hexanes–
ethyl acetate (2.3 : 1) afforded compound 18 (58 mg, 0.099
mmol, 83%) as an oil; [α]2D2 Ϫ32.0 (c 1.16, CDCl3); m/z (FAB)
589.3380 [(M ϩ H)ϩ, C32H53O6Si2 requires 589.3381], 589
(10%), 181 (25), 91 (100), 73 (25). NMR data are given in
Table 1.
References
1 B. G. Winchester and G. W. J. Fleet, Glycobiology, 1992, 2, 199.
2 Iminosugars as Glycosidase Inhibitors. Nojirimycin and Beyond, ed.
A. E. Stütz, Wiley-VCH, Weinheim, 1999.
3 H. Paulsen and K. Todt, Chem. Ber., 1967, 100, 512.
4 L. Poitout, Y. Le Merrer and J.-C. Depezay, Tetrahedron Lett., 1994,
35, 3293.
5 R. A. Farr, A. K. Holland, E. W. Huber, N. P. Peet and P. M.
Weintraub, Tetrahedron, 1994, 50, 1033.
6 B. B. Lohray, Y. Jayamma and M. Chatterjee, J. Org. Chem., 1995,
60, 5958.
7 F. Morís-Varas, X. Qian and C.-H. Wong, J. Am. Chem. Soc., 1996,
118, 7647.
8 X. Qian, F. Morís-Varas, M. C. Fitzgerald and C.-H. Wong, Bioorg.
Med. Chem., 1996, 4, 2055.
9 Y. Le Merrer, L. Poitout, J.-C. Depezay, I. Dosbaa, S. Geoffroy and
M.-J. Foglietti, Bioorg. Med. Chem., 1997, 5, 519.
10 P. R. Andreana, T. Sanders, A. Janczuk, J. I. Warrick and
P. G. Wang, Tetrahedron Lett., 2002, 43, 6525.
11 C. C. Joseph, H. Regeling, B. Zwanenburg and G. J. F. Chittenden,
Tetrahedron, 2002, 58, 6907.
12 J. N. Tilekar, N. T. Patil, H. S. Jadhav and D. D. Dhavale,
Tetrahedron, 2003, 59, 1873.
13 G. F. Painter, P. J. Elridge and A. Falshaw, Bioorg. Med. Chem.,
2004, 12, 225.
14 G. F. Painter and A. Falshaw, J. Chem. Soc., Perkin Trans. 1, 2000,
1157.
2,5-Di-O-benzyl-3,4-bis-O-(tert-butyldimethylsilyl)-L-ido-
hexodialdose (19)
A solution of NaIO4 (30 mg, 0.14 mmol) in water (2 mL) was
added to a stirred solution of the diol 18 (40 mg, 0.068 mmol) in
acetonitrile (5 mL) and the mixture was heated at 65 ЊC for 6 h.
After cooling, toluene (10 mL) was added and the solvents were
removed under reduced pressure. The residue was partitioned
between ethyl acetate (100 mL) and brine (100 mL), the aque-
ous phase was re-extracted with ethyl acetate (2 × 100 mL) and
the combined organic extracts were dried (MgSO4). The solvent
was removed under reduced pressure to give the crude product
that was purified by column chromatography. Gradient elution
with hexanes–ethyl acetate (9 : 1
4 : 1) afforded dialdehyde 19
(33 mg, 0.056 mmol, 82%) as an oil; [α]2D2 ϩ54 (c 0.66, CDCl3);
1H NMR (CDCl3) δ Ϫ0.04 (6 H, s, Me), 0.00 (6 H, s, Me), 0.82
(18 H, s, Me), 3.93–4.00 (2 H, m, 2,5- or 3,4-H), 4.03–4.10 (2 H,
m, 3,4- or 2,5-H), 4.41 (2 H, d, J 11.6, PhCH2), 4.62 (2 H, d,
J 11.6, PhCH2), 7.21–7.31 (10 H, m, Ar), 9.72 (2 H, s, CHO);
13C NMR. (CDCl3) δ Ϫ4.2 (q), 18.3 (s), 26.2 (q), 73.3 (t), 75.1
(d), 84.3 (d), 128.4 (d), 128.7 (d), 128.8 (d), 137.5 (s), 201.8 (d);
m/z (FAB) 587.3214 [(M ϩ H)ϩ, C32H51O6Si2 requires 587.3224],
797 (1%), 587 (1%), 277 (5), 181 (10), 91 (100), 73 (15).
15 A. Falshaw, J. B. Hart and P. C. Tyler, Carbohydr. Res., 2000, 329,
301.
16 C. Liu, R. J. Davis, S. R. Nahorski, S. Ballereau, B. Spiess and
B. V. L. Potter, J. Med. Chem., 1999, 42, 1991.
17 E. A. Shneour and C. E. Ballou, J. Am. Chem. Soc., 1958, 80, 3960.
18 T. Mikami, H. Asano and O. Mitsunobu, Chem. Lett., 1987, 2033.
19 B. M. Malle, I. Lundt and R. H. Furneaux, J. Carbohydr. Chem.,
2000, 19, 573.
20 J. Honeyman and C. J. G. Shaw, J. Chem. Soc., 1959, 2454.
21 E. L. Eliel and H. Satici, J. Org. Chem., 1994, 59, 688.
22 M. A. Tius and J. Busch-Petersen, Tetrahedron Lett., 1994, 35, 5181.
23 T. Hosoya, Y. Ohashi, T. Matsumoto and K. Suzuki, Tetrahedron
Lett., 1996, 37, 663.
24 H. Yamada, M. Nakatani, T. Ikeda and Y. Marumoto, Tetrahedron
Lett, 1999, 40, 5573.
N-Benzyl-3,6-di-O-benzyl-4,5-bis-O-(tert-butyldimethylsilyl)-L-
ido-3,4,5,6-tetrahydroxyazepane (20)
Benzylamine (15 µL, 0.14 mmol) was added to a stirred mixture
of the dialdehyde 19 (33 mg, 0.056 mmol), NaCNBH3 (10 mg,
0.16 mmol), AcOH (17 µL, 0.30 mmol) and 3 Å sieves (200 mg)
in MeOH (5 mL) at Ϫ78 ЊC under argon. The reaction mixture
was allowed to warm to room temperature over 18 h, then
filtered through Celite. The solvent was removed from the
filtrate under reduced pressure and the residue was partitioned
between ethyl acetate (50 mL) and NaHCO3 (saturated, aque-
ous 50 mL). The aqueous phase was further extracted with ethyl
acetate (2 × 50 mL) and the combined organic extracts were
dried (MgSO4). After filtration, the solvent was removed under
reduced pressure to give the crude product that was purified by
column chromatography. Gradient elution with CH2Cl2–
25 S. Shuto, M. Terauchi, Y. Yahiro, H. Abe, S. Ishikawa and
A. Matsuda, Tetrahedron Lett, 2000, 41, 4151.
26 H. Abe, S. Shuto and A. Matsuda, J. Am. Chem. Soc., 2001, 123,
11870.
27 E. J. Corey, H. Cho, C. Rücker and D. H. Hua, Tetrahedron Lett.,
1981, 22, 3455.
28 J. D. Stevens and H. G. Fletcher, J. Org. Chem., 1968, 33, 1799.
29 G. Kotowycz and R. U. Lemieux, Chem. Rev., 1973, 73, 669.
30 R. U. Lemieux and A. A. Pavia, Can. J. Chem., 1968, 46, 1453.
31 R. U. Lemieux, A. A. Pavia, J. C. Martin and K. A. Watanabe,
Can. J. Chem., 1969, 47, 4427.
32 D. H. Whiffen and J. H. Brewster, J. Am. Chem. Soc., 1959, 81, 5483;
R. U. Lemieux and J. C. Martin, Carbohydr. Res., 1970, 13, 139.
33 A. Ault, J. Chem. Educ., 1970, 47, 812.
34 H. Paulsen, W. von Deyn and W. Röben, Liebigs Ann. Chem., 1984,
433.
MeOH (1 : 0
200 : 1) afforded the title compound (22 mg,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 0 0 7 – 1 0 1 2
1012