Synthesis of new fucose-containing carbohydrate derivatives

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 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, 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 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. 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.

Description

technical field [0001] The present invention relates to the enzymatic synthesis of fucooligosaccharide glycosides. Background technique [0002] Human milk oligosaccharides (HMOs) are of great interest as they are directly associated with unique biological activities such as antibacterial, antiviral, immune system and cognitive development enhancing activities. HMOs were found to act as prebiotics within the human intestinal system, helping to develop and maintain the intestinal flora. Furthermore, they have also been shown to be anti-inflammatory substances, so they are used in the nutritional industry for the production of e.g. infant formula, infant cereals, clinical infant nutrition, toddler formula, etc., or as a Dietary supplements or health functional foods for women or breastfeeding women are attractive ingredients, whether as synthetically manufactured or naturally occurring compounds and their salts. HMOs are also of interest in the pharmaceutical industry for th...

AI Technical Summary

Problems solved by technology

[0007] Due to the wide variety of oligosaccharides present in libraries from natural sources such as human milk, isolation techniques have not been able to provide large quantities of fucoidal oligosaccharides

In addition, the presence of regioisomers characterized by closely similar structures makes separation techniques unsuccessful

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