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M. Adinolfi et al. / Tetrahedron Letters 42 (2001) 5971–5972
treatment afforded the expected monobenzylated
methyl a-glucopyranosides as the sole detectable prod-
ucts (TLC, NMR). Solid-phase debenzylations were
then attempted suspending the resins 1–4 in the double
liquid phase (water and ethyl acetate) in the presence of
excess NaBrO3 and Na2S2O4. The resulting mixture was
kept under vigorous horizontal stirring overnight.10
Subsequent cleavage with 32% aq. ammonia afforded
completely deprotected methyl a-glucopyranoside in all
cases. In order to prove the potential of the procedure
in oligosaccharide synthesis, the polymer bound accep-
tor 1a was glycosylated with imidate 5 under the previ-
ously reported conditions6a to afford disaccharide 6 in
good overall yield (90%) after detachment and depro-
tection with ammonia. In an initial attempt to link a
nucleotide through a secondary hydroxyl of a glucose
residue, support 2a obtained with this procedure was
subjected to automated coupling with phosphoramidite
7 under the standard phosphoramidite protocol.11
Detachment from the resin provided the dimeric conju-
gate 8 in an unoptimized 56% yield.12
formed at the Centro di Metodologie Chimico-Fisiche
dell’Universita` di Napoli.
References
1. Kocienski, P. J. In Protecting groups; Enders, D.; Noyori,
R.; Trost, B. M., Eds.; Georg Thieme Verlag: New York,
1994.
2. Lobron, L.; Hindsgaul, O. J. Am. Chem. Soc. 1999, 121,
5835–5836.
3. Egusa, K.; Fukase, K.; Nakai, Y.; Kusumoto, S. Synlett
2000, 27–32.
4. Obadiah, J. P.; Buchwald, S. L.; Seeberger, P. H. J. Am.
Chem. Soc. 2000, 122, 7148–7149.
5. Kanie, O.; Grotenbreg, G.; Wong, C.-H. Angew. Chem.,
Int. Ed. Engl. 2000, 39, 4545–4546.
6. (a) Adinolfi, M.; Barone, G.; De Napoli, L.; Iadonisi, A.;
Piccialli, G. Tetrahedron Lett. 1998, 39, 1953–1956; (b)
Adinolfi, M.; Barone, G.; De Napoli, L.; Guariniello, L.;
Iadonisi, A.; Piccialli, G. Tetrahedron Lett. 1999, 40,
2607–2610; (c) Adinolfi, M.; De Napoli, L.; Di Fabio, G.;
Guariniello, L.; Iadonisi, A.; Messere, A.; Montesarchio,
D.; Piccialli, G. Synlett 2001, 745–748.
OH
O
OBz
O
BzO
BzO
HO
HO
O
O
HO
HO
HO
BzO
OC(=NH)CCl3
HO
6
5
OCH3
7. (a) Collins, P.; Ferrier, R. Monosaccharides; J. Wiley and
Sons: New York, 1995; (b) Hanessian, S. Preparative
Carbohydrate Chemistry; Marcel Dekker: New York,
1997.
O
N
O
CH3
CH3
HN
HN
O
O
O
O
N
HO
DMTO
8. Adinolfi, M.; Barone, G.; Guariniello, L.; Iadonisi, A.
Tetrahedron Lett. 1999, 40, 8439–8441.
O
OP(N-i-Pr)2
HO
9. For very recent applications of this methodology in car-
bohydrate chemistry, see: (a) Adinolfi, M.; Barone, G.;
Iadonisi, A.; Mangoni, L. Synlett 2000, 1277–1278; (b)
Du, Y.; Zhang, M.; Kong, F. Org. Lett. 2000, 2, 3797–
3800.
P
O
7
8
CH3O
O
OH
OH
O
HO
10. Typical experimental procedure for the solid-phase
debenzylation: a solution of sodium thiosulfate (85%, 56
mg, 0.27 mmol) in water (1.5 mL) was slowly added
dropwise to a mixture of CPG resin (200 mg) functional-
ized with a benzylated sugar (40–60 mmol per g of resin,
8–12 mmol), ethyl acetate (1.5 mL) and a solution of
NaBrO3 (48 mg, 0.32 mmol) in water (1.5 mL). The
mixture was kept under vigorous horizontal stirring (200
rotations per minute) overnight. The resin was filtered
and then washed repeatedly with water, methanol and
dichloromethane. The detachment and the simultaneous
removal of acetyl groups were performed by treating the
support with 32% aq. ammonia for 3 hours at room
temperature.
In conclusion, we have shown that unmodified benzyl
protecting groups can be removed from polymer bound
monosaccharides by the two phase NaBrO3/Na2S2O4
method. It should be noted that the procedure
described can be successfully applied on the CPG resin,
while the application on polystyrene based resins could
be limited by the ability of the NaBrO3/Na2S2O4 system
to effect radical brominations of benzylic positions. On
the other hand, the efficiency of the described solid-
phase deprotection despite the use of a double liquid
phase is of note.
Acknowledgements
11. Gait, M. J. Oligonucleotide Synthesis: A Practical
Approach; IRL Press: Oxford, 1984.
1
12. Selected H NMR (D2O, 300 MHz) data for 8: 7.44 (1H,
s, thymidine H-6), 6.17 (1H, t; J=6.5 Hz, thymidine
H-1%), 4.81 (1H, d; J=3.8 Hz, glucose H-1), 3.23 (3H, s,
-OCH3).
Financial support by MURST (PRIN 2000-2001),
CNR and Universita` di Napoli (Progetto Giovani
Ricercatori) is acknowledged. NMR spectra were per-
.