970
O. Šimák et al. / Carbohydrate Research 344 (2009) 966–971
1H, J3,NH 9.7 Hz, NHAc), 6.44 (br s, 1H, NH-ring). 13C NMR (CDCl3): d
19.1 (C-6), 20.9 and 20.9 (2 ꢁ COCH3), 23.4 (NHCOCH3), 50.2 (C-5),
52.0 (C-3), 70.6 (C-2), 72.7 (C-4), 167.0 (C-1), 170.5 (NHCOCH3),
171.0 and 171.2 (2 ꢁ COCH3). Anal. Calcd for C12H18N2O6: C,
50.35; H, 6.34; N, 9.7. Found: C, 50.51; H, 6.32; N, 10.00.
53.1 (OCH3), 67.2 (C-4), 71.1 (C-2), 153.8 (C-5), 168.2 (C-1), 170.0
and 170.1 (2 ꢁ COCH3), 170.1 (NHCOCH3).
3.9. 3-Acetamido-1,3,5-trideoxy-1,5-imino-D-glucitol (1)
For 13: ½a 2D0
ꢂ
+75 (c 1.3, CHCl3), MS (FAB) calcd for C14H21N2O8
To a soln of lactam 13 (0.11 g; 0.32 mmol) in THF (5 ml) was
added LiAlH4 (200 mg; 5 mmol). The reaction mixture was stirred
under argon for 5 h and after this period the reaction was
quenched by addition of SiO2. The solvent was removed under vac-
uum and chromatography on silica gel (iPrOH/H2O 4:1) yielded
deoxynojirimycin analogue 1 (0.05 g; 77%) as colourless solid.
[M+H+]: 345.3. Found m/z 345.0. 1H NMR (CDCl3): d 1.93 (s, 3H,
NHCOCH3), 2.09 (s, 6H, 2 ꢁ OAc), 2.13 (s, 3H, OAc), 3.83 (m, 1H,
H-5), 4.00 (dd, 1H, J6a,6b 11.8, J5,6a 6.5 Hz, H-6a), 4.23(dd, 1H, J5,6b
2.6, J6a,6b 11.8 Hz, H-6b), 4.70 (ddd, 1H, J2,3 10.8, J3,4 10.6, J3,NH
9.7 Hz, H-3), 5.06 (dd, 1H, J3,4 10.6, J4,5 10.6 Hz, H-4), 5.17 (d, 1H,
J2,3 10.8 Hz, H-2), 6.01 (d, 1H, J3,NH 9.7 Hz, NHCOCH3), 6.51 (br s,
1H, NH-ring). 13C NMR (CDCl3): d 20.8, 20.8 and 20.9 (3 ꢁ COCH3),
23.1 (NHCOCH3), 51.7 (C-3), 53.6 (C-5), 63.3 (C-6), 67.9 (C-4), 70.0
(C-2), 162.8 (C-1), 170.7 (COCH3), 170.8 (NHCOCH3), 170.9 and
171.00 (2 ꢁ COCH3). Anal. Calcd for C14H20N2O8: C, 48.84; H,
5.85; N, 8.14. Found: C, 48.80; H, 6.01; N, 8.10.
For 1: ½a 2D0
ꢂ
+45 (c 0.5, H2O), lit.22 +40; MS (APEI) calcd for
C8H17N2O4 [M+H+]: 205.2. Found m/z 205.0. 1H NMR (D2O): d
1.90 (s, 3H, NHCOCH3), 2.42 (dd, 1H, J1ax,1eq 12.2, J1ax,2 11.3 Hz,
H-1ax), 2.52 (m, 1H, H-5), 3.07 (dd, 1H, J1ax,1eq 12.2, J1eq,2 5.3 Hz,
H-1eq), 3.14 (dd, 1H, J3,4 9.7, J4,5 9.7 Hz, H-4), 3.40 (ddd, 1H, J1ax,2
11.3, J2,3 9.7, J1eq,2 5.3 Hz, H-2), 3.49 (dd, 1H, J6a,6b 12.0, J5,6a
4.1 Hz, H-6a), 3.56 (dd, 1H, J2,3 9.7, J3,4 9.7 Hz, H-3); 3.69 (dd, 1H,
J6a,6b 12.0, J5,6 2.9 Hz, H-6b). 13C NMR (D2O): d 22.3 (NHCOCH3),
49.2 (C-1), 59.7 (C-3), 61.0 (C-6), 62.5 (C-5), 65.8 (C-2), 69.6 (C-
4), 175.2 (NHCOCH3). Anal. Calcd for C8H16N2O4: C, 47.05; H,
7.90; N, 13.72. Found: C, 51.17; H, 8.44; N, 14.82.
3.7. Methyl 3-acetamido-2,4-di-O-acetyl-3,6-dideoxy-D-xylo-
hex-5-ulosonate (18)
Methyl 3-acetamido-3,6-dideoxy-b-D-glucopyranoside 17 (0.40 g,
1.3 mmol)25 was diluted with AcOH (7.6 mL) and Ac2O (0.7 mL),
CrO3 (0.26 g, 2.6 mmol) was added at 55 °C and the mixture was stir-
red for 2 h. The reaction was quenched by EtOH (1 mL) and the sol-
vent was evaporated. The residue dissolved in CHCl3 was purified
by flash chromatography (CHCl3/MeOH 40:1). Methyl 3-acetam-
3.10. 3-Acetamido-1,3,5,6-tetradeoxy-1,5-imino-D-glucitol (2)
Following the protocol described in Section 3.9 and starting
from lactam 12 (0.11 g; 0.38 mmol) dideoxynojirimycin 2 (0.06 g;
86%) was obtained as a colourless solid.
ido-2,4-di-O-acetyl-3,6-dideoxy-D-xylo-hex-5-ulosonate (18) was
isolated (0.39 g, 92%) as colourless oil.
For 2: ½a 2D0
ꢂ
+88 (c 0.4, H2O), MS (APEI) calcd for C8H17N2O3
For 18: ½a 2D0
ꢂ
+18 (c 1.7, CHCl3). MS (FAB) calcd for C13H20NO8
[M+H+]: 189.22. Found m/z 189.1. 1H NMR (D2O): d 1.05 (d, 3H,
J5,6 6.2 Hz, H-6), 1.89 (s, 3 H, NHCOCH3), 2.47 (dd, 1H, J1ax,1eq
12.0, J1ax,2 11.4 Hz, H-1ax), 2.57 (m, 1H, H-5), 2.95 (dd, 1H, J3,4
9.7, J4,5 9.7 Hz, H-4), 3.06 (dd, 1H, J1ax,1eq 12.0 Hz, J1eq,2 4.7 Hz, H-
1eq), 3.42 (ddd, 1H, J1ax,2 11.4, J2,3 10.0 Hz, J1eq,2 4.7 Hz, H-2), 3.53
(dd, 1H, J2,3 10,0, J3,4 9.7 Hz, H-3). 13C NMR (D2O): d 16.7 (C-6),
22.3 (NHCOCH3), 49.0 (C-1), 55.8 (C-5), 59.4 (C-3), 68.9 (C-2),
74.1 (C-4), 175.2 (NHCOCH3). Anal. Calcd for C8H16N2O3: C,
51.05; H, 8.57; N, 14.88. Found: C, 51.17; H, 8.44; N, 14.82.
[M+H+]: 318.3. Found m/z 318.0. 1H NMR (CDCl3): d 1.87 (s, 3H,
NHCOCH3), 2.01 (s, 3H, OAc), 2.03 (s, 3H, OAc), 2.10 (s, 3H, H-6),
3.63 (s, 3H, OCH3), 4.97 (ddd, 1H, J2,3 4.1, J3,4 2.4, J3,NH 10.0 Hz, H-3),
5.08 (d, 1H, J2,3 4.1 Hz, H-2), 5.18 (d, 1H, J3,4 2.4 Hz, H-4), 6.38 (d,
1H, J3,NH 10.0 Hz, NHCOCH3). 13C NMR (CDCl3): d 20.5 and 20.6
(2 ꢁ COCH3), 22.9 (NHCOCH3), 26.6 (C-6), 48.8 (C-3), 52.9 (OCH3),
70.7 (C-2), 76.6 (C-4), 168.1 (C-1), 169.4 and 169.5 (COCH3), 170.1
(NHCOCH3), 170.1 (C-5). Anal. Calcd for C13H19NO8: C, 49.21; H,
6.04; N. 4.41. Found: C, 49.65; H, 5.97; N, 4.28.
Acknowledgement
3.8. Methyl 3-acetamido-2,4-di-O-acetyl-3,6-dideoxy-D-xylo-
hex-5-ulosonate oxime (19)
This work was supported by the Ministry of Education, Youth
and Sports of the Czech Republic (project MSM 6046137305).
To a soln of ulosonate 18 (0.39 g, 1.21 mmol) in pyridine
(0.9 mL), NH2OHꢃHCl (0.11 g, 1.6 mmol) was added at 0 °C. After
15 min the reaction mixture was allowed to reach rt and stirring
continued for 2 h. The solvent was evaporated, the residue was dis-
solved in CHCl3 and purified by flash chromatography on silica gel
(CHCl3/MeOH 40:1). A crystalline mixture of (Z/E)-oxime 19 (ratio
2:1) was obtained (0.34 g, 85%). MS (FAB) calcd for C13H21N2O8
[M+H+]: 333.3. Found m/z 333.2. Anal. Calcd for C13H20N2O8: C,
46.99; H, 6.07; N, 8.43. Found: C, 47.10; H, 6.02; N, 8.36.
References
1. Melo, E. B.; Gomes, A. D.; Carvalho, I. Tetrahedron 2006, 62, 10277–10302.
2. Compain, P.; Martin, O. R. Curr. Top. Med. Chem. 2003, 3, 541–560.
3. Compain, P.; Martin, O. R. Bioorg. Med. Chem. 2001, 9, 3077–3092.
4. Asano, N. Glycobiology 2003, 13, 93R–104R.
5. Wrodnigg, T. M.; Steiner, A. J.; Ueberbacher, B. J. Anti-Cancer Agents Med. Chem.
2008, 8, 77–85.
6. Butters, T. D. Curr. Opin. Chem. Biol. 2007, 11, 412–418.
7. Somsak, L.; Nagy, V.; Hadady, Z.; Docsa, T.; Gergely, P. Curr. Pharm. Des. 2003, 9,
1177–1189.
8. Greimel, P.; Spreitz, J.; Stutz, A. E.; Wrodnigg, T. M. Curr. Top. Med. Chem. 2003,
3, 513–523.
9. Nishimura, Y. Curr. Top. Med. Chem. 2003, 3, 575–591.
10. Butters, T. D.; Dwerk, R. A.; Platt, F. M. Glycobiology 2005, 15, R43–R52.
11. Robina, I.; Moreno-Vargas, A. J.; Carmona, A. T.; Vogel, P. Curr. Drug Metab.
2004, 5, 329–361.
12. Butters, T. D.; Dwerk, R. A.; Platt, F. M. Curr. Top. Med. Chem. 2003, 3, 561–574.
13. Butters, T. D.; Dwerk, R. A.; Platt, F. M. Chem. Rev. 2000, 100, 4683–4696.
14. Murphy, P. V.; Dunne, J. L. Curr. Org. Synth. 2006, 3, 403–437.
15. Cipolla, L.; La Ferla, B.; Nicotra, F. Curr. Top. Med. Chem. 2003, 3, 485–511.
For major 19: 1H NMR (CDCl3): d 1.94 (s, 3H, H-6), 1.97 (s, 3H,
NHCOCH3), 2.09 (s, 3H, OAc), 2.18 (s, 3H, OAc), 3.73 (s, 3H,
OCH3), 4.95 (ddd, 1H, J2,3 2.3, J3,4 7.9, J3,NH 10.0 Hz, H-3), 5.05 (d,
1H, J2,3 2.3 Hz, H-2), 5.47 (d, 1H, J3,4 7.9 Hz, H-4), 5.92 (d, 1H,
J3,NH 10.0 Hz, NHCOCH3), 8.19 (br s, 1H, OH). 13C NMR (CDCl3): d
10.8 (C-6), 20.7 and 21.0 (2 ꢁ COCH3), 23.2 (NHCOCH3), 50.3 (C-
3), 53.1 (OCH3), 71.1 (C-2), 73.4 (C-4), 153.5 (C-5), 168.1 (C-1),
169.9 and 170.3 (2 ꢁ COCH3), 170.3 (NHCOCH3).
For minor 19: 1H NMR (CDCl3): d 1.89 (s, 3H, H-6), 1.99 (s, 3H,
NHCOCH3), 2.09 (s, 3H, OAc), 2.18 (s, 3H, OAc), 3.73 (s, 3H,
OCH3), 4.96 (ddd, 1H, J2,3 2.3, J3,4 7.0, J3,NH 9.1 Hz, H-3), 5.02 (d,
1H, J2,3 2.3 Hz, H-2), 5.95 (d, 1H, J3,NH 9.1 Hz, NHCOCH3), 6.28 (d,
1H, J3,4 7.0 Hz, H-4), 8.45 (br s, 1H, OH). 13C NMR (CDCl3): d 15.9
(C-6), 20.7 and 20.9 (2 ꢁ COCH3), 23.3 (NHCOCH3), 50.1 (C-3),
}
16. de Raadt, A.; Ekhard, C. W.; Ebner, M.; Stutz, A. E. Glycoscience—Synthesis of
Substrate Analogs and Mimetics, 1st ed.; Springer: Berlin/Heidelberg, 1997. pp
157–186.
17. Baxter, E. W.; Reitz, A. B. J. Org. Chem. 1994, 59, 3175–3185.
18. Pearson, M. S. M.; Mathe-Allainmat, M.; Fargeas, V.; Lebreton, J. Eur. J. Org.
Chem. 2005, 11, 2159–2191.
19. Polt, R.; Sames, D.; Chruma, J. J. Org. Chem. 1999, 64, 6147–6158.