handle is critical for the conjugation of the carbohydrate
epitopes to any carrier of interest and thereby increases the
scope of biological studies that can be performed with these
compounds. A selectively protected serine residue was
introduced at the reducing terminus as an aglycone. Fur-
thermore, because serine is located at the reducing terminus
in natural oligosaccharides of this type, compounds 1-4 are
biologically relevant.
The synthesis was initiated with compound 5,9 which was
deprotected with 20% triethylamine (TEA) in MeOH to
provide triol 6, an intermediate common to all structures
(Scheme 1). Triol 6 was then divergently converted to 7 or
Figure 1. Structure of sulfoadhesin with core 1 and core 6 branches
highlighted.
Scheme 1. Synthesis of R-GalNAc-Serine
specific contribution of each branch to L-selectin binding has
not been directly measured.
To evaluate the individual contributions of the sulfoadhesin
branches to L-selectin binding, the synthesis of 6-O-sulfated
oligosaccharides corresponding to core 1 (1) and core 6 (2)
branches and their nonsulfated counterparts (3, 4) was
undertaken (Figure 2). Although sulfated oligosaccharides
8 for the synthesis of the core 1 and core 6 structures,
respectively. The use of an N-phthalimido group was deemed
to be incompatible with the protecting groups of the serine
residue. Therefore, the 2-N-phthalimido (NPht) group of 910
was replaced with a 2-N-2′,2′,2′-trichloroethylcarbonyl
(NHTroc) group to provide 10 in a three-step procedure
(Scheme 2).
To maximize the efficiency of the synthesis of hexasac-
charides 1 and 3, a route was developed that incorporated
two key regioselective glycosylation reactions. Known
compound 1111 was reacted with 7 using N-iodosuccinimide
(NIS) and trifluoromethanesulfonic acid (TfOH) as promoters
to give the disaccharide in good yield with complete
regioselectivity (Scheme 2). The acetyl esters of this disac-
charide were then removed to provide 12. Compound 12 was
condensed with 10 under identical conditions to yield
tetrasaccharide 13, again with complete regioselectivity and
in excellent yield for this type of unprecedented transforma-
tion.
Figure 2. Synthetic targets corresponding to core 1 (1) and core
6 (2) branches and their nonsulfated counterparts (3 and 4,
respectively).
similar to 1 and 2 have been synthesized previously by other
groups,8 the incorporation of reactive functional groups at
their reducing termini has not been reported. Such a reactive
Over the next three steps, 13 was converted to 17 using
standard protecting group manipulations (Scheme 3). First,
the 6-O-TBS and 4,6-O-benzylidene groups were removed
(7) (a) Hemmerich, S.; Leffler, H.; Rosen, S. D. J. Biol. Chem. 1995,
270, 12035-12047. (b) Yeh, J.-C.; Hiraoka, N.; Petryniak, B.; Nakayama,
J.; Ellies, L. G.; Rabuka, D.; Hindsgaul, O.; Marth, J. D.; Lowe, J. B.;
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(8) (a) Jain, R. K.; Huang, B.-G.; Chandrasekaran, E. V.; Matta, K. L.
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Y.; Lowe, J. B.; Hindsgaul, O. Bioorg. Med. Chem. Lett. 2000, 10, 1505-
1509. (d) Belot, F.; Rabuka, D.; Fukuda, M.; Hindsgaul, O. Tetrahedron
Lett. 2002, 43, 7743-7747.
(9) Ferrari, B.; Pavia, A. A. Carbohydr. Res. 1980, 79, C1-C8.
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Org. Lett., Vol. 6, No. 14, 2004