738
3
Chemical Glycosylation Reactions
mw
microwave
NIS
N-iodosuccinimide
TESOTf triethylsilyl triflate
1 Introduction
Anomeric anhydro sugars are sugar derivatives in which the anomeric carbon participates in an
acetal linkage with two of the hydroxyl groups of the sugar. They are essentially intramolecular
glycosides, which may be formally derived from the parent sugar by the loss of a molecule of
water. Importantly, the intramolecular acetalation of the anomeric center acts to protect this
position and two other hydroxyl groups. The bicyclic structure of anomeric anhydro sugars
ensures that they are restricted to a limited conformational coordinate that strongly influences
the reactivity of the remaining hydroxy groups. Many anhydro sugars are highly crystalline
and this feature makes them easy compounds to work with and to purify. This chapter focuses
on anomeric anhydro sugars of synthetic utility and on the more common reactions known for
this class of sugars.
1.1 General Remarks
Solutions of aldohexoses in aqueous acid at equilibrium contain varying amounts of anhydro
sugars, particularly the 1,6-forms. The composition of the equilibrium mixture has been determined for a number of aldohexoses in the presence of acidic ion-exchange resin or in 0.25-M
H 2 SO 4 at 100 °C [1]. For D-glucose and D-galactose, the proportion of anhydro sugars present
at equilibrium is small; for D-altrose, D-gulose, and D-idose the proportion of the 1,6-anhydropyranose present is greater than 50%. The formation of 1,6-anhydrofuranoses under these
conditions is much less favorable. Of the eight aldohexoses, D-talose forms an anhydrofuranose to the greatest degree and, in this case, only to the extent of 2.5%. As a rule, as the
number of hydroxy groups oriented in the axial direction in the ‘usual’ 4 C 1 conformation
of an aldose increases, so does its tendency to form 1,6-anhydro derivatives. The acetal of
anomeric anhydro sugars may be cleaved by solvolysis under acidic conditions. In the absence
of a nucleophilic solvent, Lewis acid-catalyzed polycondensation of anomeric anhydro sugar
monomers affords glycans. This approach provides an efficient method for the preparation of
certain stereoregular polysaccharides [2].
2 1,6-Anhydrohexopyranoses
2.1 Occurrence and Formation
Of all the anhydro sugars, 1,6-anhydrohexopyranoses are the most studied and are of the greatest synthetic utility. 1,6-Anhydrohexopyranoses have been the subject of several comprehensive reviews, which the interested reader should consult for more details [3,4,5,6]. 1,6-Anhydro-β-D-glucopyranose (1; > Fig. 1) (also known as ‘glucosan’ or ‘levoglucosan’ on account
3
Chemical Glycosylation Reactions
mw
microwave
NIS
N-iodosuccinimide
TESOTf triethylsilyl triflate
1 Introduction
Anomeric anhydro sugars are sugar derivatives in which the anomeric carbon participates in an
acetal linkage with two of the hydroxyl groups of the sugar. They are essentially intramolecular
glycosides, which may be formally derived from the parent sugar by the loss of a molecule of
water. Importantly, the intramolecular acetalation of the anomeric center acts to protect this
position and two other hydroxyl groups. The bicyclic structure of anomeric anhydro sugars
ensures that they are restricted to a limited conformational coordinate that strongly influences
the reactivity of the remaining hydroxy groups. Many anhydro sugars are highly crystalline
and this feature makes them easy compounds to work with and to purify. This chapter focuses
on anomeric anhydro sugars of synthetic utility and on the more common reactions known for
this class of sugars.
1.1 General Remarks
Solutions of aldohexoses in aqueous acid at equilibrium contain varying amounts of anhydro
sugars, particularly the 1,6-forms. The composition of the equilibrium mixture has been determined for a number of aldohexoses in the presence of acidic ion-exchange resin or in 0.25-M
H 2 SO 4 at 100 °C [1]. For D-glucose and D-galactose, the proportion of anhydro sugars present
at equilibrium is small; for D-altrose, D-gulose, and D-idose the proportion of the 1,6-anhydropyranose present is greater than 50%. The formation of 1,6-anhydrofuranoses under these
conditions is much less favorable. Of the eight aldohexoses, D-talose forms an anhydrofuranose to the greatest degree and, in this case, only to the extent of 2.5%. As a rule, as the
number of hydroxy groups oriented in the axial direction in the ‘usual’ 4 C 1 conformation
of an aldose increases, so does its tendency to form 1,6-anhydro derivatives. The acetal of
anomeric anhydro sugars may be cleaved by solvolysis under acidic conditions. In the absence
of a nucleophilic solvent, Lewis acid-catalyzed polycondensation of anomeric anhydro sugar
monomers affords glycans. This approach provides an efficient method for the preparation of
certain stereoregular polysaccharides [2].
2 1,6-Anhydrohexopyranoses
2.1 Occurrence and Formation
Of all the anhydro sugars, 1,6-anhydrohexopyranoses are the most studied and are of the greatest synthetic utility. 1,6-Anhydrohexopyranoses have been the subject of several comprehensive reviews, which the interested reader should consult for more details [3,4,5,6]. 1,6-Anhydro-β-D-glucopyranose (1; > Fig. 1) (also known as ‘glucosan’ or ‘levoglucosan’ on account