O-sulfated derivatives of glucuronic acid

Article abstract of DOI:10.3390/50300600

4-O-Substituted D-glucuronic acid derivatives were synthesized from D-glucose in order to study the regioselectivity of sulfation.

Full text of DOI:10.3390/50300600

600
Molecules 2000, 5
O-Sulfated Derivatives of Glucuronic Acid
Mariano J. L. Castro, Natalia Salmaso, José Kovensky and Alicia Fernández Cirelli
Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR, CONICET), Departamento de
Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad
Universitaria, Pab. II, 3er. Piso, 1428 Buenos Aires, Argentina
E-mail: mcastro@qo.fcen.uba.ar, jose@qo.fcen.uba.ar, afc@rec.uba.ar
Abstract: 4-O-Substituted D-glucuronic acid derivatives were synthesized from D-glucose
in order to study the regioselectivity of sulfation.
Introduction
Glycosaminoglycans, as heparin and heparan sulfate, interact with various proteins, and their bind-
ing properties are related to the glycosidic sequence and the number and position of sulfate groups. In
our laboratory, we performed a variety of chemical modifications of the polysaccharide chain. On sul-
fation of heparan sulfate, the regioselective sulfation of glucuronic acid units in O-2 has been ob-
served.1 This result is interesting due to biological properties of heparan sulfate.
Experimental
The synthesis of derivatives of glucuronic acid was performed as shown in Fig. 1.
OH
OH
Ph
O
O
iii
i
ii
O
HO
BnO
O
HO
HO
O
OMe
OMe
OMe
OMe
BnO
OBn
OH
OBn
1
3
2
COOBn
COO-Na+
OTBS
O
O
O
iv MeO
BnO
MeO
HO
v
MeO
BnO
OMe
OMe
OBn
OH
OBn
4
5
6
+
i. Ph(OMe) 2, PTSA; NaH, BnBr. ii. MeOH, H . iii. TBSCl, Et 3N, DMAP; MeOTf.
iv. H2SO4, CrO3, acetone. v. H , Pd-C.
2
Figure 1.

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Molecules 2000, 5
Sulfation of 6 was accomplished with SO3.Et3N in DMF in the reaction conditions employed for
heparan sulfate. The products were purified by chromatography and characterized by NMR (1H and
13C).
Results and Discussion
Sulfation of methyl 4,6-O-benzylidene D-glucopyranoside, and methyl 4-O-benzoyl-D-
glucopyranosiduronate showed no selectivity 2- and 3-O-sulfated derivatives. This result is in accor-
dance with previous reports on similar reactivity of HO-2 and HO-3 in acylation reactions of com-
pounds of D-gluco configuration.
The selectivity observed in heparan sulfate would therefore be related to the structure of the glyco-
sidic chain. In this polysaccharide, the regular sequence is composed by a β-D-glucuronic acid unit
linked to HO-4 of N-acetyl or N-sulfate-D-glucosamine residue. The linking of the glucosamine to the
next glucuronate is α, giving an alternating sequence. This anomeric configuration would allow the
formation of hydrogen bonds between both residues, involving the HO-3 of glucuronic acid units, pre-
venting their sulfation. Oligosaccharide models needed to study this hypothesis can be prepared from
compound 3.
Acknowledgements: The authors are indebted to the Universidad de Buenos Aires (UBA) and the Con-
sejo Nacional de Investigaciones Científicas y Técnicas (CONICET) for financial support. A.F.C. and
J.K. are Resarch Members of the CONICET.
References and Notes
1. Kovensky, J.; Fernández Cirelli, A. Carbohydr. Res. 1997, 303, 119.