Glycosyl donor
Encyclopedia
A glycosyl donor is a carbohydrate mono- or oligosaccharide that will react with a suitable glycosyl acceptor
to form a new glycosidic bond
. By convention, the donor is the member of this pair that contains the resulting anomer
ic carbon of the new glycosidic bond. The resulting reaction is referred to as a glycosylation
or Chemical glycosylation
.
In a glycosyl donor, a leaving group
is required at the anomeric position. The simplest leaving group is the OH group that is naturally present in monosaccharides, but it requires activation by acid catalysis in order to function as leaving group (in the socalled Fischer glycosylation). More effective leaving groups are in general used in the glycosyl donors employed in chemical synthesis of glycosides. Typical leaving groups are halide, thioether, or imidate, but acetate, phosphate, and O-pentenyl are also employed. The natural glycosyl donors contain phosphate as leaving group.
The so-called “armed-disarmed” principle.
The concept of armed and disarmed glycosyl donors refers to the increased reactivity of benzylated over benzoylated glycosyl donors, a phenomenon observed very early, and which originates from the greater electron-withdrawing capability of ester blocking groups over ether blocking groups. However, it was Bertram Fraser-Reid
who realised that benzylated glycosyl donors can be activated when benzoylated are not, and invented the terms armed glycosyl donor to the former and disarmed glycosyl donor to the latter. He and his group showed that armed glycosyl donors could be coupled onto a glycosyl acceptor, that at the same time was a disarmed glycosyl donor, without selfcoupling of the disarmed donor/acceptor. This methodology allowed him to perform a one-pot synthesis of a trisaccharide via the O-pentenyl method.
The concept has been extended to superarmed glycosyl donor by Mikael Bols
and his collaborators. He realised that hydroxylic functional groups of carbohydrates are less electronwithdrawing toward the anomeric center when they are axial than equatorial, which means that glycosyl donor conformers with more axial oxy funtions are more reactive. Protection of a glycosyl donor with bulky silyl groups (tert butyldimethylsilyl or triisopropyl) cause it to change conformation to a more axial-rich conformation that, as a consequence, is more reactive, which Bols and his groups called superarmed. They showed that a superarmed donor can be coupled on to an armed glycosyl donor/acceptor.
Glycosyl acceptor
A glycosyl acceptor is any suitable nucleophile-containing molecule that will react with a glycosyl donor to form a new glycosidic bond. By convention, the acceptor is the member of this pair which did not contain the resulting anomeric carbon of the new glycosidic bond...
to form a new glycosidic bond
Glycosidic bond
In chemistry, a glycosidic bond is a type of covalent bond that joins a carbohydrate molecule to another group, which may or may not be another carbohydrate....
. By convention, the donor is the member of this pair that contains the resulting anomer
Anomer
In carbohydrate chemistry, an anomer is a special type of epimer. It is one of two stereoisomers of a cyclic saccharide that differs only in its configuration at the hemiacetal or hemiketal carbon, also called the anomeric carbon. Anomerization is the process of conversion of one anomer to the other...
ic carbon of the new glycosidic bond. The resulting reaction is referred to as a glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
or Chemical glycosylation
Chemical glycosylation
A chemical glycosylation reaction involves the coupling of a sugar to a glycosyl acceptor forming a glycoside. If the acceptor is another sugar, the product is an oligosaccharide. The reaction involves coupling a glycosyl donor to a glycosyl acceptor via activation utilizing a suitable activator...
.
In a glycosyl donor, a leaving group
Leaving group
In chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl−, Br−, and I−, and sulfonate esters, such as para-toluenesulfonate...
is required at the anomeric position. The simplest leaving group is the OH group that is naturally present in monosaccharides, but it requires activation by acid catalysis in order to function as leaving group (in the socalled Fischer glycosylation). More effective leaving groups are in general used in the glycosyl donors employed in chemical synthesis of glycosides. Typical leaving groups are halide, thioether, or imidate, but acetate, phosphate, and O-pentenyl are also employed. The natural glycosyl donors contain phosphate as leaving group.
The so-called “armed-disarmed” principle.
The concept of armed and disarmed glycosyl donors refers to the increased reactivity of benzylated over benzoylated glycosyl donors, a phenomenon observed very early, and which originates from the greater electron-withdrawing capability of ester blocking groups over ether blocking groups. However, it was Bertram Fraser-Reid
Bertram Fraser-Reid
Bertram Oliver "Bert" Fraser-Reid is a synthetic organic chemist who has been widely recognized for his work using carbohydrates as starting materials for chiral materials and on the role of oligosaccharides in immune response....
who realised that benzylated glycosyl donors can be activated when benzoylated are not, and invented the terms armed glycosyl donor to the former and disarmed glycosyl donor to the latter. He and his group showed that armed glycosyl donors could be coupled onto a glycosyl acceptor, that at the same time was a disarmed glycosyl donor, without selfcoupling of the disarmed donor/acceptor. This methodology allowed him to perform a one-pot synthesis of a trisaccharide via the O-pentenyl method.
The concept has been extended to superarmed glycosyl donor by Mikael Bols
Mikael Bols
Mikael Bols is a synthetic organic chemist who is mainly known for his work on carbohydrates and artificial enzymes.-Early life:Mikael Bols was born and grew up in Copenhagen, Denmark...
and his collaborators. He realised that hydroxylic functional groups of carbohydrates are less electronwithdrawing toward the anomeric center when they are axial than equatorial, which means that glycosyl donor conformers with more axial oxy funtions are more reactive. Protection of a glycosyl donor with bulky silyl groups (tert butyldimethylsilyl or triisopropyl) cause it to change conformation to a more axial-rich conformation that, as a consequence, is more reactive, which Bols and his groups called superarmed. They showed that a superarmed donor can be coupled on to an armed glycosyl donor/acceptor.