1194
C. Liu et al. / Tetrahedron Letters 54 (2013) 1192–1194
O
N
OH
BnO
BnO
O
N
O
OCH3
4
1
2
7
a
OCH3
11
BnO
BnO
+
10
6
5
12
8
9
3
BnO
OBn
BnO
OBn
BnO
OBn
BnO
OBn
3
7
5
HO
H
N
b
HO
O
OCH3
HO
OH
HO
OH
2
Scheme 3. Reagents and conditions: (a) Et2Zn, toluene, 91%; (b) EtOH, 5% Pd/C, 6 N HCl, H2, 20 atm, 86%.
inseparable mixture of E/Z-oxime 13 under conditions described by
Tamura.14 Selective O-silylation with TBDMSCl, followed by mesy-
lation with methanesulfonyl chloride afforded an oxime derivative
15,15 which was desilylated with anhydrous TBAF in THF at 0 °C in
62% isolated yield for the compound 16, together with smaller
amounts (28%) of nitrone 3. However, changed reaction condition
did not provide large quantity of nitrone 3, which was obtained
by treatment of the compound 16 with hydroxylamine under basic
conditions in 92% isolated yield.16
Supplementary data
Supplementary data associated with this article can be found,
References and notes
1. Aslam, T.; Fuchs, M. G. G.; Formal, A. L.; Wightman, R. H. Tetrahedron Lett. 2005,
46, 3249–3252.
2. Liautard, V.; Desvergnes, V.; Martin, O. R. Tetrahedron: Asymmetry 2008, 19,
1999–2002.
3. Szczepina, M. G.; Zheng, R. B.; Completo, G. C.; Lowary, T. L.; Pinto, B. M.
ChemBioChem 2009, 10, 2052–2059.
4. Pedersen, L. L.; Turco, S. J. Cell. Mol. Life Sci. 2003, 60, 259–266.
5. Pan, F.; Jackson, M.; Ma, Y.; McNeil, M. R. J. Bacteriol. 2001, 183, 3991–3998.
6. Umesiri, F. E.; Sanki, A. K.; Boucau, J.; Ronning, D. R.; Sucheck, S. J. Med. Res. Rev.
2010, 30, 290–326.
7. Richard, E. L.; Martin, D. S.; Robert, J. N.; Rhodri, C. G.; Michael, M.; Ravinder, K.
G.; Wenxin, Y.; Gurdyal, S. B.; Patrick, J. B.; George, W. J. F. Tetrahedron Lett.
1997, 38, 6733–6736.
8. Liautard, V.; Desvergnes, V.; Martin, O. R. Tetrahedron: Asymmetry 2008, 19,
1999–2002.
9. Duff, F. J.; Vivien, V.; Wightman, R. H. Chem. Commun. 2000, 2127–2128.
10. Pinet, S.; Pandya, S. U.; Chavant, P. Y.; Ayling, A.; Vallée, Y. Org. Lett. 2002, 4,
1463–1466.
11. Burgos, E.; Salmon, L. Tetrahedron Lett. 2004, 45, 3465–3469.
12. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 36, 3769–3772.
13. Liautard, V.; Christina, A. E.; Desvergnes, V.; Martin, O. R. J. Org. Chem. 2006, 71,
7337–7345.
Reaction of the nucleophilic addition of L-arabinofurano-alkyne
5 to the iminogalactitol-derived nitrone 3 was carried out in the
presence of a substoichiometric amount of diethylzinc in toluene
to afford a protected pseudo-disaccharide with a very high degree
of regio- and stereoselectivity (Scheme 3). Only one product as a
single stereoisomer was observed and isolated. Indeed, compound
7
17 was isolated in 91% yield after chromatography. The NMR data
confirmed that the C–C bond formation had taken place at the ter-
minal position of the alkynyl group, as predicted from Vallee’s
studies.10 Furthermore, the detected NOE interactions between
H-7 and H-9 provided evidence for a b-configuration of the newly
created C–C bond. From the structure of product thus determined,
it is inferred that the nucleophilic addition took place highly selec-
tively in an exo-anti mode, namely, by addition to the least
hindered Si face of nitrone (anti with respect to the substituent
at C-2) and with the alkyne substituent in the exo direction. Finally,
under hydrogenolytic conditions, compound 7 was converted into
the novel Galf-disaccharide mimic 2.18
In conclusion, the nucleophilic addition of 5–3 is noteworthy, in
that it provides a means of coupling alkynyl sugar to nitrone by a
carbon–carbon linkage in the presence of diethylzinc in toluene,
and thus opens a concise approach to a diversity of disaccharide
mimics incorporating an iminogalactitol moiety. The resulting
compound is a potential inhibitor of mycobacterial UDP-Galf trans-
ferases, and its biological investigation is currently in process.
14. Bernet, B.; Mangholz, S. E.; Riner, K. B.; Vasella, A. Helv. Chim. Acta 2003, 86,
1488–1521.
15. Liu, C. Y.; Gao, J. C.; Yang, G.; Wightman, R. H.; Jiang, S. D. Lett. Org. Chem. 2007,
4, 556–558.
16. Desvergnes, S.; Vannick, S.; Py, V. J. Org. Chem. 2005, 70, 1459–1462.
17. Selected data for 7: dH (400 MHz): 3.37 (3H, s, OCH3), 3.40–3.46 (1H, m), 3.70–
3.75 (2H, m), 3.96–3.98 (2H, m), 4.12–4.18 (3H, m), 4.33 (1H, m, H-7), 4.40–
4.68 (12H, m, OCH2Ph), 4.75 (1H, dd, J = 6.9 Hz, J = 2.0 Hz, H-4), 4.97 (1H, d,
J = 1.5 Hz, H-1), 5.52 (1H, s, N-OH), 7.23–7.42 (30H, m, ArH); MS-EI (m/z): 898
(M++Na); Anal. Calcd for C55H57NO9: C, 75.41; H, 6.56; N, 1.60. Found: C, 75.47;
H, 6.62; N, 1.55.
18. Selected data for 2: dH (300 MHz, D2O): 1.48–1.87 (4H, m, H-5 & H-6), 2.71–3.06
(2H, m, H-7 & H-10), 3.36 (3H, s, OCH3), 3.53–4.08 (8H, m), 4.72 (1H, s, H-1);
MS-EI (m/z): 346 (M++Na); Anal. Calcd for C13H25NO8: C, 48.29; H, 7.79; N, 4.33.
Found: C, 48.22; H, 7.84; N, 4.35.
Acknowledgment
The authors are grateful for the research support from the
Natural Science Foundation of Hebei Province (No. 2010001761).