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US 2014/0228554 A1Published application
Synthesis of new fucose-containing carbohydrate derivatives
AssigneeGlycom A/S
InventorsElise Champion, Gyula Dekany, Markus Hederos, Karoly Agoston
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Abstract
A method for the synthesis of a fucooligosaccharide glycosides by reacting a fucosyl donor with H-A-R1 or a salt thereof, wherein A and R1 are as defined herein, under the catalysis of an enzyme capable of transferring fucose is provided. The fucooligosaccharid glycoside compounds, or derivatives thereof, their use in the manufacture of human milk oligosaccharides, and a method of manufacture of human milk oligosaccharides, are also provided.
Claims19
A method for the synthesis of a compound of formula 1 or a salt thereof,
- wherein A is a carbohydrate linker which is a lactosyl moiety or which consists of a lactosyl moiety and at least one monosaccharide unit selected from the group consisting of:
- glucose, galactose, N-acetylglucosamine, fucose and N-acetyl neuraminic acid;
- and wherein R1 is one of the following anomeric protecting groups:
- a) —OR2, wherein R2 is a protecting group removable by catalytic hydrogenolysis,
- b) —SR3, wherein R3 is an optionally substituted alkyl, an optionally substituted aryl or an optionally substituted benzyl,
- c) —NH—C(R″)═C(R′)2, wherein each R′ independently is one of the following electron withdrawing groups:
- —CN, —COOH, —COO-alkyl, —CO-alkyl, —CONH2, —CONH-alkyl or —CON(alkyl)2, or wherein the two R′-groups are linked together and form —CO—(CH2)2-4—CO— and thus form, together with the carbon atom to which they are attached, a 5-7 membered cycloalkan-1,3-dione, in which dione any of the methylene groups is optionally substituted with 1 or 2 alkyl groups, and R″ is H or alkyl,
- characterized in that a fucosyl donor of formula 2
- wherein X is selected from the group consisting of:
- a guanosine diphosphatyl moiety, a lactose moiety, azide, fluoride, optionally substituted phenoxy-, optionally substituted pyridinyloxy-, optionally substituted 3-oxo-furanyloxy- of formula A, optionally substituted 1,3,5-triazinyloxy- of formula B, 4-methylumbelliferyloxy-group of formula C, and a group of formula D
- wherein Ra is independently H or alkyl, or two vicinal Ra groups represent a ═C(Rb)2 group, wherein Rb is independently H or alkyl, Rc is independently selected from the group consisting of alkoxy, amino, alkylamino and dialkylamino, Rd is selected from the group consisting of H, alkyl and —C(═O)Re, wherein Re is OH, alkoxy, amino, alkylamino, dialkylamino, hydrazino, alkylhydrazino, dialkylhydrazino or trialkylhydrazino, is reacted with an acceptor of formula H-A-R1 or a salt thereof, wherein A and R1 are as defined above, under the catalysis of an enzyme capable of transferring fucose.
8 more elements
A compound of formula 1 or a salt thereof,
- wherein A is a carbohydrate linker which is a lactosyl moiety or which consists of a lactosyl moiety and at least one monosaccharide unit selected from the group consisting of:
- glucose, galactose, N-acetylglucosamine, fucose and N-acetyl neuraminic acid, and wherein R1 is one of the following anomeric protecting groups:
- a) —OR2, wherein R2 is a protecting group removable by catalytic hydrogenolysis,
- b) —SR3, wherein R3 is an optionally substituted alkyl, an optionally substituted aryl or an optionally substituted benzyl,
- c) —NH—C(R″)═C(R′)2, wherein each R′ independently is one of the following electron withdrawing groups:
- —CN, —COOH, —COO-alkyl, —CO-alkyl, —CONH2, CONH-alkyl or —CON(alkyl)2, or wherein the two R′-groups are linked together and form —CO—(CH2)2-4—CO— and thus form, together with the carbon atom to which they are attached, a 5-7 membered cycloalkan-1,3-dione, in which dione any of the methylene groups is optionally substituted with 1 or 2 alkyl groups, and R″ is H or alkyl,
- provided that if R1 is —OR2 then linker A does not comprise N-acetyl neuraminic acid.
4 more elements
(canceled)
(canceled)
A method of manufacture of a human milk oligosaccharide or a salt thereof, comprising the step of removing the anomeric protecting group R1 from a compound of formula 1′ or a salt thereof
- wherein A is a carbohydrate linker which is a lactosyl moiety or which consists of a lactosyl moiety and at least one monosaccharide unit selected from the group consisting of:
- glucose, galactose, N-acetylglucosamine, fucose and N-acetyl neuraminic acid;
- and wherein R1 is one of the following anomeric protecting groups:
- a) —OR2, wherein R2 is a protecting group removable by catalytic hydrogenolysis,
- b) —SR3, wherein R3 is an optionally substituted alkyl, an optionally substituted aryl or an optionally substituted benzyl,
- c) —NH—C(R″)═C(R′)2, wherein each R′ independently is one of the following electron withdrawing groups:
- —CN, —COOH, —COO-alkyl, —CO-alkyl, —CONH2, —CONH-alkyl or —CON(alkyl)2, or wherein the two R′-groups are linked together and form —CO—(CH2)2-4—CO— and thus form, together with the carbon atom to which they are attached, a 5-7 membered cycloalkan-1,3-dione, in which dione any of the methylene groups is optionally substituted with 1 or 2 alkyl groups, and R″ is H or alkyl,
- provided that if R1 is —OR2 then linker A does not comprise N-acetyl neuraminic acid.
5 more elements
A compound of formula 2A
- wherein Ra is independently H or alkyl, or two vicinal Ra groups represent a ═C(Rb)2 group, wherein Rb is independently H or alkyl, and preferably wherein Ra is independently H, methyl or ethyl.
Dependencies are inferred from the claim text.