Notes and references
† A minor amount of the corresponding a-1,3 derivative was also isolated
3–5%.
‡ When the reaction was carried out at 0 °C in the presence of 1.7 equiv. of
glycosyl donor 1, a tetrasaccharide resulting from the glycosylation of 1 at
positions O-3 and O-4 in 8 was the only isolated compound (68%).
§ Selected data: for 8: [a]D 25.7 (c 0.5, CHCl3); for 9: [a]D +17.6 (c 1,
CHCl3), API-ES positive (M+Na+): m/z 961.2; for 13: [a]D 235.5 (c 0.9,
CHCl3), API-ES positive (M+Na+): m/z 1007.5.
¶ Hydrolysis of the anomeric thiophenyl group was also observed.
∑ Other attempts to carry out the one-pot glycosylation with premixed 1 and
6 (e.g. CH2Cl2, TfOAg 0.3 equiv., 0.03 M, 213 °C, 20 min) gave complex
reaction mixtures.
** Three other saccharides (10–15%) were also present in the reaction
mixture, possibly resulting from the glycosidic coupling of 11 with
hydrolyzed 6.
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Scheme 3
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Another interesting aspect of our results, with implications in
the success of the synthetic scheme, is the striking difference in
behavior between glycosyl donors 1 and 11, which is illustrated
by the contrast between the results in Scheme 3(b) and 3(c).
Thus, while one-pot glycosylation of 6 and 1 [Scheme 3(b)]
resulted in the formation of pseudotrisaccharide 10 (with the
intermolecular glycosylation taking place prior to the tethered
cyclo-glycosylation), the one-pot glycosylation of 6 and 11
[Scheme 3(c)] yielded trisaccharide 12, as the major isomer
formed,** where the cyclo-glycosylation had preceded the
intermolecular glycosyl coupling. The tuning of donor re-
activity, by changes in the protecting group at O-6, in
mannopyranosyl donors, 1 and 11, is thus responsible for this
behavior,22 and, in our opinion, when coupled to further tuning
between intra- and inter-molecular glycosidic coupling could
open a new avenue for the preparation of branched saccharides
and small saccharide libraries.
The procedures outlined here, although not yet optimized,
serve to illustrate a novel concept for one-pot glycosylation
which relies in the kinetic acceleration of an intramolecular
versus an intermolecular glycosidic coupling rather than in large
disparities between the reactivities of different glycosyl donors.
The optimization of this protocol by changes in the concentra-
tion and/or nature of the glycosyl donors is currently under
study.
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This research was supported with funds from the Dirección
General de Enseñanza Superior (grants: PB96-0822 and PB97-
1244). M. G. thanks the Ministerio de Educación y Cultura for
a predoctoral scholarship.
814
Chem. Commun., 2000, 813–814