Synthesis of core sugar chain structure of aspargine-linked glycoprotein
AssigneeShionogi & Co., Ltd.
InventorsShinichiro Nishimura, Yasuhiro Takegawa
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Abstract
It is intended to chemically synthesize the trisaccharide moiety at the reducing end in the core sugar chain structure of an asparagine-linked glycoprotein. By using a highly inexpensive natural polysaccharide having a mannoseβ-1,4-bond as the starting material, a β-1,4-glycoside bond of mannose is formed.
Claims10
A method for preparing a trisaccharide (Manβ1→4GlcNβ1→4GlcN) of the reducing terminal in the core sugar chain structure of an asparagine-linked glycoprotein, comprising
- (1) a process of preparing a mannose disaccharide compound (a type of ManP1β1→4ManP1) of the formula (I)
- wherein P1 is an OH-protecting group and the wavy line means that —OP1 is linked at an axial or equatorial position or mixture of both, by hydrolyzing a polysaccharide having mannoseβ-1,4-bonds and protecting OH groups of the resulting hydrolysate.
A method for preparing a mannose disaccharide compound (a type of ManP1β1→4ManP1) shown with the formula (I);
- wherein P1 is an OH-protecting group and the wavy line means that —OP1 is linked at an axial or equatorial position or mixture of both,
- by hydrolyzing a polysaccharide having mannoseβ-1,4-bonds and protecting OH groups of the resulting hydrolysate.
A method for preparing the azide disaccharide (a type of ManP1β1→4ManP1) shown with the formula (II) in which the 2-azide group of mannose in the reducing terminal is linked at the equatorial position;
- wherein P1 is an OH-protecting group, and the wavy line means that —NO2 is linked at an axial or equatorial position or mixture of both, comprising a process of preparing a glycal compound, in which mannose of the reducing terminal of the mannose disaccharide is converted to glycal, by halogenation and reduction of the mannose disaccharide compound (a type of ManP1β1→4ManP1) shown with the formula (I);
- wherein P1 is the same above and the wavy line means that —OP1 is linked at an axial or equatorial position or mixture of both,
- and subsequent azidenitration reaction of the glycal compound.
A method for preparing the trisaccharide compound shown with the formula (III);
- wherein P1, P2, P3 and P11 are the same above,
- comprising a process of substituting the nitro group of the azide disaccharide compound (a type of ManP1β1→4ManP1) shown with the formula (II) with a leaving group;
- wherein P1 is the same above, the wavy line means that —NO2 is linked at an axial or equatorial position or mixture of both, and the 2-azide group of mannose in the reducing terminal is linked at the equatorial position,
- and next, reacting the substituted compound having the leaving group with amino-protected glucopyranoside of the formula;
- wherein P2 is an OH-protecting group, P3 is an amino-protecting group and P11 is an OH-protecting group.
A method for preparing an asparagine-linked trisaccharide compound (Manβ1→4GlcNP1β1→4GlcNP2) shown with the formula (IV)
- wherein P1 and P2 are the same above, P4 and P6 are independently amino-protecting groups and P5 is a carboxyl-protecting group,
- by coupling of the reducing terminal of the trisaccharide compound (III)
- wherein P1, P2, P3 and P11 are the same above,
- with a protected asparagine derivative.
The azide disaccharide (a type of ManP1β1→4ManP1) compound shown with the formula (II);
- wherein P1 is an OH-protecting group, and the wavy line means that —NO2 is linked at an axial or equatorial position or mixture of both.
The trisaccharide compound (a type of Manβ1→4GlcNP1β1→4GlcNP2) shown with the formula of (III);
- wherein P1, P2 and P11 are OH-protecting group, and P3 is an amino-protecting group.
Dependencies are inferred from the claim text.