7272
F. Labe´gue`re et al. / Tetrahedron Letters 43 (2002) 7271–7272
converted into 1-bis(methylthio)methyl-2,3,4,6-tetra-O-
advance in C-glycosidic chemistry. We are now focus-
ing on the diastereoselective synthesis of C-glycosyl-
aminoacids using 5 as a building block.
benzyl-a- -glucopyranose 3 according to the method
D
described by Fukase et al.11 The b pure glycosylalde-
hyde 5 was obtained as the only b anomer after two
additional steps. The synthetic pathway is outlined in
Scheme 1.
Acknowledgements
This work was supported by the Ministe`re de l’Educa-
2,3,4,6-Tetra-O-benzyl-
D
-glucono-1,5-lactone
2
was
obtained by oxidation of 1.12 After completion, addi-
tion of water and extraction with ethyl acetate was
sufficient to obtain 2 in 99% yield without any further
purification. The second step, described by Fukase,11
was the umpolung Seebach reaction of 2 with bis-
(methylthio)methyl carbanion. Fukase obtained 1-C-
tion Nationale, France.
References
1. Kawasaki, M.; Matsuda, F.; Terashima, S. Tetrahedron
Lett. 1986, 27, 2145.
[bis(methylthio)methyl]-a- -glucopyranose 3 in 80%
D
2. Okabe, T.; Nomoto, K.; Funabashi, H.; Okuda, S.;
Suzuki, T.; Tanaka, N. J. Antibiot. Ser. 1985, 38, 1336.
3. Lo¨ffler, A.; Doucey, M.-A.; Jansson, A. M.; Mu¨ller, D.;
de Beer, T.; Hess, D.; Meldal, M.; Richter, W.; Vliegen-
thart, J.; Hofsteenge, J. Biochemistry 1996, 35, 12005.
4. Hanessian, S. Total Synthesis of Natural Products. The
Chiron Approach; Pergamon Press: Oxford, 1983.
5. Shulman, M.; Svetlana, D.; Shiyan, S.; Khorlin, A. Car-
bohydr. Res. 1974, 33, 229.
6. Kate, W.; Tang, M.; Suzuki, T.; Kitajima, K.; Inoue, Y.;
Inoue, S.; Fan, J.-Q.; Lee, Y. J. Am. Chem. Soc. 1997, 46,
11137.
7. Martin, O.; Khamis, F.; Rao, S. Tetrahedron Lett. 1989,
30, 6143.
8. Dondoni, A.; Schermann, M.-C. Tetrahedron Lett. 1993,
34, 7319.
9. Bertozzi, C.; Bernarski, M. Tetrahedron Lett. 1992, 33,
3019.
10. Reed, L.; Ito, Y.; Masamune, S.; Sharpless, K. J. Am.
Chem. Soc. 1982, 104, 6468.
11. Fukase, H.; Horri, S. J. Org. Chem. 1992, 57, 3642.
12. Kuzuhara, H.; Fletcher, H., Jr. J. Org. Chem. 1967, 32,
2531.
yield by action of n-butyllithium on the corresponding
bis(methylthio)methane using two equivalents of bis-
(methylthio)methane and of n-butyllithium.11 However,
in our hands, these conditions afforded 3 in only 40%
yield. Four equivalents of bis(methylthio)methane and
n-butyllithium were needed to obtain 3 in 74% yield.
The anomeric hydroxyl group of 3 was then stereospe-
cifically reduced by triethylsilane13 in the presence of
boron trifluoride diethyl etherate to afford the single b
anomer, b-1-bis(methylthio)methyl-tetra-O-benzyl-D-
glucopyranoside 4, in an excellent yield (99%). The b
1
configuration was assigned by H NMR spectroscopy
by measuring a 8.9 Hz coupling constant between H1
and H2.14 This value is representative of an axial/axial
coupling, only possible with a b configuration and a
chair C1 conformation (Fig. 1). Finally, dithiane alkyl-
ation and cleavage with methyl iodide and calcium
carbonate15 afforded the glycosylaldehyde 516 whose
data were identical to the b anomer described by
Dondoni.8
It is noteworthy that compound 5 could be obtained in
the same global yield by purifying only at the last step.
13. Lewis, M.; Cha, J.; Kishi, Y. J. Am. Chem. Soc. 1982,
104, 4976.
14. Compound 4 was isolated by addition of water and
extraction with ethylacetate. 4: syrup, 1H NMR (250,
CDCl3) l: 2.11 (s, 3H, CH3), 2.19 (s, 3H, CH3), 3.39–3.54
(m, 2H, H-6, H-6%), 3.59–3.74 (m, 4H, H-2, H-3, H-4,
The facile synthesis of the 1-formyl-2,3,4,6-tetra-O-benz-
yl-b-
D
-glucopyranoside 5 in pure b anomeric form is an
BnO
H-5), 3.74 (dd, 1H, JH-1,CH(SMe)(SMe)=1.6 Hz, JH-1,H-2
=
H2
SMe
8.9 Hz, H-1), 3.92 (d, 1H, JCH(SMe)(SMe),H-1=1.8 Hz,
CH(SMe)2), 4.50–4.96 (m, 8H, 4×CH2Ph), 7.17–7.32 (m,
20H, 4×Ph).
O
BnO
BnO
15. Grobel, T.; Seebach, D. Synthesis 1977, 357.
16. Compound 5 was isolated by silicagel column (9/1
petroleum ether/ethylacetate). Compound 5: 1H RMS:
[FAB+] C35H37O6 theoretic mass: 553.2592, observed
SMe
BnO
H1
4
J1-2=8.9 Hz
1
mass: 553.2590, H NMR (250, CDCl3) l: 3.43–3.50 (m,
Figure 1. b configuration and C1 conformation for 4: the
only possibility for an axial/axial coupling between H-1 and
H-2.
2H, H-6, H-6%), 3.56–3.81 (m, 4H, H-2, H-3, H-4, H-5),
4.53–4.92 (m, 9H, 4×CH2Ph, H-1), 7.12–7.29 (m, 20H,
4×Ph), 9.61 (d, 1H, JCHO,H-1=1.17 Hz, CHO).