| abstract |
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 R 1 is one of the following anomeric protecting groups: a) -OR 2 , wherein R 2 is a protecting group removable by catalytic hydrogenolysis; b) -SR 3 , wherein R 3 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, -CONH 2 , -CONH- alkyl or -CON(alkyl) 2 , or wherein the two R'-groups are linked together and form -CO-(CH 2 ) 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, in which 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 R a is independently H or alkyl, or two vicinal R a groups represent a =C(R b ) 2 group, wherein R b is independently H or alkyl, R c is independently selected from the group consisting of alkoxy, amino, alkylamino and dialkylamino, R d is selected from the group consisting of H, alkyl and -C(=O)R e , wherein R e is OH, alkoxy, amino, alkylamino, dialkylamino, hydrazino, alkylhydrazino, dialkylhydrazino or trialkylhydrazino, is reacted with an acceptor of formula H-A-R 1 or a salt thereof, wherein A and R 1 are as defined above, under the catalysis of an enzyme capable of transferring fucose. A compound of formula 1', its use in manufacture of human milk oligosaccharides, a method of manufacture of human milk oligosaccharides, and a fucosyl donor are also provided. |