K. P. Ravindranathan Kartha et al. / Carbohydrate Research 339 (2004) 729–732
731
Although satisfactory results were obtained in the
above reactions, the necessity to use methanol obtained
by storage over molecular sieves for extended periods
proved limiting. As an alternative, use of HPLC grade
MeOH in combination with powdered molecular sieves
was examined.9 When a solution of the per-O-acetylated
glucose 3 was stirred at room temperature in the pres-
deacetylation reaction rates were somewhat slower
(approximately 2-fold) than noted above.
2.2.2. Method B: HPLC grade MeOH + powdered,
˚
activated 4 A molecular sieves. A mixture of the acyl-
ꢀ
ated sugar derivative and powdered, activated 4 A
molecular sieves (equal in weight to that of the sugar) in
HPLC grade MeOH (approximately 2–4 ml per 100 mg
of acetylated sugar) was stirred at room temperature.
Following completion of the reaction (Table 2), filtra-
tion and concentration in vacuo gave the product in
near quantitative yield. In the preparation of 19a, the
pure product was obtained in 90% yield after purifica-
tion by chromatography on a column of silica gel using
dichloromethane/MeOH (97:3) as eluent.
ꢀ
ence of powdered, activated 4 A molecular sieves (equal
in weight to that of the sugar derivative) conversion to
the fully deprotected 4 was complete in 36 h (Table 2,
entry 1). Likewise, lactose octa-O-acetates 16 gave
lactose 17 in excellent yield (entry 2). Per-O-acetylated
N-acetyl glucosamine 18, on the other hand, gave the
hemiacetal 19 (entry 3), a useful precursor to the cor-
responding glycosyl trichloroacetimidate,10 in 90% yield
in around 2 h. Fully deprotected N-acetylglucosamine 20
was obtained on continuation of the reaction for 48 h.
Acknowledgements
ꢀ
In summary, we have shown that activated 4 A
molecular sieves can effect useful selective and complete
de-O-acylation of sugar derivatives and that the process
is notably milder than Zemplen conditions. Although in
some contexts such trans-esterification reactions may be
desirable, clearly the use of molecular sieves as drying
agents in glycosylation reactions employing esterified
building blocks needs to be considered with caution.
We thank the MRC, EPSRC and the Weston Founda-
tion for financial support. We gratefully acknowledge
the EPSRC Mass Spectrometry Service Centre, Swansea
for invaluable support.
References
1. Breck, D. W.; Eversole, W. G.; Milton, R. M.; Reed,
T. B.; Thomas, T. L. J. Am. Chem. Soc. 1956, 78, 5963–
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2. Aldrich Technical Information Bulletin, No. AL-143,
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4. Pellets (1.6 mm), supplied by Aldrich, UK (Catalogue no
33,430-8).
ꢀ
5. An aqueous slurry (5%) of 4 A molecular sieves, 4–8 mesh,
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2. Experimental
2.1. General
All compounds described in this study have been
reported previously: 1 and 211, 3–5 and 16–2012, 6–713,
8–914, 10–1315, 14 and 1516; several are commercially
available.
2.2. Procedures for the preparation and use of
methanolic sodium methoxide solution
2.2.1. Method A: MeOH extensively dried over activated
˚
4 A molecular sieves. MeOH was stored for at least
ꢀ
8 weeks over pelleted 4 A molecular sieves. Methanolic
sodium methoxide prepared in this fashion was used
(approximately 2–4 ml per 100 mg of acetylated sugar) to
effect deacylation. Reactions were carried out at room
temperature and were typically complete in <45 min
(Table 1, entries 1–5) and <2 h (Table 1, entries 6 and 7),
respectively. Products were obtained in essentially
quantitative yield, except entry 8 where the yield was
70%. All compounds were judged pure by proton NMR
spectroscopy.
8. Adinolfi, M.; Barone, G.; Iadonisi, A.; Schiattarella, M.
Tetrahedron Lett. 2003, 44, 4661–4663.
2
ꢀ
9. Although the effective radius of methanol is 4.4 A, both 3
ꢀ
or 4 A powdered molecular sieves proved effective in
de-O-acetylation reactions, although reactions employing
the former were noticeably slower.
10. Grundler, G.; Schmidt, R. R. Liebigs Ann. Chem. 1984,
1826–1847.
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Whistler, R. L., Wolfrom, M. L., Eds.; Academic: New
Alternatively, methanolic sodium methoxide was
prepared from HPLC grade MeOH by refluxing over
ꢀ
pelleted 4 A molecular sieves for 10 h. Subsequent