FREE-RADICAL THIOL-ENE AND THIOL-YNE COUPLINGS AS CLICK PROCESSES FOR GLYCOCONJUGATION - Click Chemistry in Glycoscience: New Developments and Strategies - page 44

Thiol-ene Thiol-yne

R 1

R 2 S

RS

S SH

R '

R SH

R 1 R 2 R 1

R 1

S

R S

RS S S

R '

S

R 1 R 2 R 1

R 1 R 2

SH S

R ' R 1 R 1 R 2

SCHEME 3.1 Mechanisms of photoinduced thiol-ene and thiol-yne coupling.

appeared to be quite important to validate this prerogative by using these reactions
in a field dealing with complex, multifunctionalized and delicate molecules such
as carbohydrates. Therefore, this chapter illustrates the results obtained in our own
laboratory on the use of both TEC and TYC in the construction of various S -linked
glycoconjugates. These include oligosaccharides, glycodendrimers and glycoclus-
ters, glycosyl aminoacids and glycopeptides. The glycoconjugation of a protein is
described as well. The aim of our work was to extend the scope of these reactions
in organic and bioorganic chemistry as their use in these fields is quite limited [7] in
comparison to the numerous applications in polymer and material sciences [8, 9].

3.2 S -LINKED OLIGOSACCHARIDES

Oligosaccharides and glycoconjugates deeply influence many fundamental biological
processes in living organisms [10]. They mediate a variety of events, including
inflammation, immunological response, fertilization, cancer metastasis, viral, and
bacterial infections [11]. Hence, usable quantities of natural carbohydrates with a
well-defined structure and composition are needed to study those phenomena at
molecular level. There is, however, substantial difficulty to obtain complex natural
O -linked oligosaccharides in a pure and homogeneous form from natural sources
because of the presence of mixtures of glycosylated species (glycoforms). Moreover
these compounds display an intrinsic instability toward chemical and enzymatic
degradation due to the labile exocyclic carbon-oxygen bond. Therefore, synthetic
efforts have been directed toward the supply of carbon- and sulfur-linked isosteres,
that is, compounds bearing a methylene group or a sulfur atom in place of the oxygen
atom of the glycosidic bond that is present in natural products (Fig. 3.2). Thus, simple
C -disaccharides [12] and S -disaccharides [13] have been mainly prepared because
these products can be used as probes of recognition specificity and may provide
important insight into the mechanism of glycoside elaboration by carbohydrate-
processing enzymes. In turn, these glycomimetics may become effective inhibitors of