Y. Bl e´ riot et al. / Carbohydrate Research 340 (2005) 2713–2718
2717
was dissolved in dry THF (70 mL) under N in the pres-
ence of 4 A molecular sieves. The soln was cooled to
C, 57.73; H, 9.15; N, 7.48. Found C, 57.26; H, 9.40;
N, 7.24. HRMS: Calcd for MH : 188.1286; Found:
2
+
˚
ꢀ
78 ꢁC. Methyl lithium (18 mL, 25.2 mmol, 1.4 M soln
in diethyl ether) was added and the soln stirred at
78 ꢁC. After 2 h, TLC (1:1 EtOAc/hexane) showed
no starting material (R 0.62) and a new product (R
188.1278. Physical data for enantiomer (ꢀ)-11: Mp
2
D
3
23
183–184 ꢁC; ½aꢁ ꢀ77 (c 1, CHCl ).
3
ꢀ
3.1.5. 1,5-Imino-1,5,6-trideoxy-D-galactitol (+)-1. 1,5-
Imino-3,4-O-isopropylidene-1,5,6-trideoxy-D-galactitol
(+)-11 (133 mg, 0.71 mmol) was dissolved in 50% aq tri-
fluoroacetic acid (4 mL) and the soln was stirred for 2 h.
The solvent was removed under diminished pressure
and co-evaporated with toluene (2 · 5 mL). Purification
by flash chromatography (20:77:3 CHCl /CH OH/
f
f
0
.72). A satd aq ammonium chloride soln (10 mL) was
added and the soln was stirred for 30 min. The reaction
mixture was then extracted with CH Cl (4 · 50 mL).
The organic extracts were combined, dried (magnesium
sulfate), filtered off and the solvent removed under
diminished pressure. The resulting yellow solid was puri-
fied by flash chromatography (1:2 EtOAc/hexane) to
give 6-azido-1,6-dideoxy-3,4-O-isopropylidene-L-lyxo-
2
2
3
3
MeOH/conc NH soln) afforded 1,5-imino-1,5,6-tride-
3
oxy-D-galactitol (+)-1 (102 mg, 96% yield), which was
2
-hexulofuranose (ꢀ)-9 (3.49 g, 91% yield) as a white
solid.
Mp 89–90 ꢁC; ½aꢁ ꢀ12.5 (c 1, CHCl ); m
freeze-dried to give a brown foam.
24
20
½aꢁ +42.2 (c 0.66, H O) (lit.: +49; c 1, H O); m
D
2
2
max
2
D
1
ꢀ1
1
(KBr):
max
(film): 3370 cm (br, OH, NH); H NMR (500 MHz,
MeOH-d ): 1.17 (3H, d, J 6.7 Hz, CH ), 2.40 (1H,
3
ꢀ
1
1
4
3
436 (br, OH), 2101 cm (N ); H NMR (500 MHz,
3
5,6
3
CDCl ): 1.33, 1.48 (6H, 2 · s, C(CH ) ), 1.54 (3H, s,
dd, J1a,2 10.9 Hz, J1a,1e 12.8, H-1a), 2.80 (1H, dq, J5,4
<0.5 Hz, H-5), 3.08 (1H, dd, J1e,2 5.3 Hz, H-1e), 3.33
3
3 2
CH ), 2.13 (1H, br, OH), 3.54 (2H, d, J
0
6.4 Hz, H-
6,6
3
0
13
6
5
, H-6 ), 4.23 (1H, app. dt, J 3.9 Hz, J5,6 6.4 Hz, H-
(1H, m, H-3), 3.75–3.70 (2H, m, H-2, H-4); C NMR
5
,4
4
), 4.48 (1H, d, J3,4 5.9 Hz, H-3), 4.78 (1H, dd, H-4);
C NMR (50 MHz, CDCl ): 22.9 (CH , C-1), 25.2,
(125 MHz, MeOH-d ): 15.7 (q, CH ), 49.4 (t, CH )
3
2
1
3
54.0 (d, C-5), 67.6, 72.2, 75.7 (3 · d, C-2, C-3, C-4);
3
3
+
2
8
6.5 (2 · CH , C(CH ) ), 50.4 (CH , C-6), 77.9, 80.9,
m/z (APCI+): 148 (MH , 100%); HRMS: Calcd for
3
3 2
2
+
5.8 (3 · CH, C-3, C-4, C-5), 105.9 (C-2), 113.4
MH : 148.0973; Found: 148.0968. Physical data for
+
23
23
(
3
C(CH ) ); m/z (APCI+): 216 (92%), 202 (MH ꢀN ,
enantiomer (ꢀ)-1: ½aꢁD ꢀ48.8 (c 0.64, H O).
3
2
2
2
+
8%), 184 (MH ꢀH OꢀN , 100%); Anal. Calcd for
2
2
C H O N : C, 47.16; H, 6.60; N, 18.33. Found: C,
9
15
4
3
4
7.38; H, 6.53; N, 18.03. Physical data for enantiomer
Acknowledgements
23
23
(
+)-9: Mp 86–87 ꢁC; ½aꢁD +16 (c 1, CHCl3).
We thank the European CommunityÕs Human Potential
Programme (under contract HPRN-CT-2002-00173) for
financial support.
3
.1.4. 1,5-Imino-3,4-O-isopropylidene-1,5,6-trideoxy-D-
galactitol (+)-11. 6-Azido-1,6-dideoxy-3,4-O-isopropy-
lidene-L-lyxo-2-hexulofuranose (ꢀ)-9 (1.0 g, 4.4 mmol)
was dissolved in EtOH (25 mL). Palladium black
(
300 mg) was added. The soln was degassed three times
References
and air was replaced by H . The soln was stirred at room
2
temperature under an atmosphere of H . After 24 h, the
2
1
. Lillelund, V. H.; Jensen, H. H.; Liang, X.; Bols, M. Chem.
Rev. 2002, 102, 515–553; St u¨ tz, A. Iminosugars as Glyco-
sidase Inhibitors: Nojirimycin and Beyond; Wiley-VCH:
Weinheim, 1999.
. Mitrakou, A.; Tountas, N.; Raptis, A. E.; Bauer, R. J.;
Schulz, H.; Raptis, S. A. Diab. Med. 1998, 15, 657–660;
Scott, L. J.; Spencer, C. M. Drugs 2000, 59, 521–549.
. Butters, T. D.; Dwek, R. A.; Platt, F. M. Curr. Top. Med.
Chem. 2003, 3, 561–574.
soln was filtered through a Celite plug eluted with
EtOH. The solvent was removed under diminished pres-
sure to give a yellow solid, which was purified by flash
2
chromatography (4:1 CHCl /MeOH) to afford 1,5-
3
imino-3,4-O-isopropylidene-1,5,6-trideoxy-D-galactitol
(
+)-11 as a white solid (700 mg, 3.7 mmol, 84% yield).
3
22
Mp 164–166 ꢁC; ½aꢁ +84.0 (c 1, CHCl ); m
(KBr):
max
D
3
ꢀ
1
1
3
434 cm (br, OH, NH); H NMR (500 MHz, CDCl ):
4. Jacob, G. S. Curr. Opin. Struct. Biol. 1995, 5, 605–611, and
3
references cited therein.
1
.27 (3H, d, J5,6 6.3 Hz, CH ), 1.38, 1.55 (6H, 2 · s,
3
5
. Mehta, A.; Ouzounov, S.; Jordan, R.; Simsek, E.; Lu, X.
Y.; Moriarty, R. M.; Jacob, G.; Dwek, R. A.; Block, T.
M. Antiviral Res. 2003, 57, 56; Greimel, P.; Spreitz, J.;
St u¨ tz, A. E.; Wrodnigg, T. M. Curr. Top. Med. Chem.
2003, 3, 513–523.
C(CH ) ), 1.95 (1H, br, OH), 2.48 (1H, dd, J
1a,2
3
2
1
2
0.6 Hz, J1e,1a 13.0 Hz, H-1a), 3.08 (1H, dq, J4,5
.6 Hz, H-5), 3.12 (1H, dd, J1e,2 5.1 Hz, H-1e), 3.67
(
1H, ddd, J2,3 7.1 Hz, H-2), 3.88 (1H, dd, J 5.3 Hz,
3,4
1
3
6
. Zitzmann, N.; Mehta, A. S.; Carrou e´ e, S.; Butters, T. D.;
Platt, F. M.; McCauley, J.; Blumberg, B. S.; Dwek, R. A.;
Block, T. M. PNAS 1999, 96, 11878–11882; Nishimura, Y.
Curr. Top. Med. Chem. 2003, 3, 575–591.
H-3), 4.04 (1H, dd, H-4); C NMR (50 MHz, CDCl3):
8.0 (CH , C-6), 26.7, 28.7 (2 · CH , C(CH ) ), 48.7
1
(
3
3
3 2
CH , C-1), 51.6 (CH, C-5), 71.1, 77.0, 80.5 (3 · CH,
2
C-2, C-3, C-4), 109.5 (C(CH ) ); m/z (APCI+): 188
3
2
7. Heightman, T. D.; Vasella, A. T. Angew. Chem., Int. Ed.
1999, 38, 750–770; Vasella, A.; Davies, G. J.; B o¨ hm, M.
+
(
MH , 100%), 130 (19%); Anal. Calcd for C H O N:
9 17 3