Method for synthesizing macromolecules in solution from carbohydrate derivative units
The invention relates to a method for synthesising macromolecules made up of units U that are mostly monosaccharides or monosaccharide derivatives, by successive elongation of a first unit U1 attached by a covalent bond to an anchor molecule soluble in organic solvents. The elongation takes place by coupling with a monomer or oligomer M having at least two functions. The method is characterised in that the anchor molecule comprises a polyolefin chain or a polyolefin oligomer or a polyalkene, with at least 5 monomer units, and preferably between 10 and 50 monomer units, the polyolefin chain preferably being a polyisobutene chain.
1 . A method for synthesizing macromolecules made up of units U that are mostly monosaccharides or monosaccharide derivatives, which may be identical or different, said macromolecules having a first and a second end, said synthesis method proceeding by successive elongation of said second end by a monomer or oligomer M having at least two functional groups, and said method being characterized in that:
in a first anchoring step, the first unit U1 of said macromolecule, corresponding to a monomer M1 or a terminal unit of an oligomer M1, is attached by a covalent bond to an anchor molecule soluble in non-polar organic solvents, said covalent bond resulting from a reaction of a first of the functional groups of said monomer M1 or of said oligomer M1 with a functional group of said anchor molecule, the second termination possibly being another functional group of said monomer M1 or of said oligomer M1 that has been protected, prior to said reaction, by at least a first protecting group GP1, and possibly by a second protecting group GP2;
in a second deprotection step, one of said protecting groups GP1 or GP2 is removed, leaving a free functional group on said monomer M1 or oligomer M1;
in a third coupling step, a second monomer M2 or oligomer M2, carrying at least one free functional group and at least one functional group protected by a protecting group GP3, is reacted so that its free functional group forms, by reaction with said free functional group of said first monomer M1 or oligomer M1, a covalent bond, thus creating a new molecule formed by said monomer M1 or oligomer M1, attached by its first end to said anchor molecule, and said monomer M2 or oligomer M2, attached to another of its terminations, and said method being characterized in that said anchor molecule comprises a polyisobutene chain with at least 5 monomer units.
2 . The method according to claim 1 , characterized in that an n-th monomer Mn or oligomer Mn is added by coupling.
3 . The method according to claim 2 , characterized in that after coupling the last monomer or oligomer, deprotection of the protecting groups of the macromolecule is carried out.
4 . The method according to claim 3 , comprising at least one step in which said macromolecule attached to said anchor molecule is separated from the reaction medium by extraction in an apolar organic solvent, and/or by extraction or washing with a polar solvent, and/or by filtration.
5 . The method according to claim 4 , comprising a step in which said macromolecule is fully deprotected.
6 . The method according to claim 5 , characterized in that said monosaccharide units or monosaccharide derivatives are pentose or hexose derivatives.
7 . The method of claim 6 , wherein the pentose derivative is in a nucleoside.
8 . The method according to claim 6 , characterized in that the bond between two successive units is a bond of the osidic type or of the carbohydrate type or of the N-heteroside type or of the S-heteroside type.
9 . The method of claim 8 , wherein the osidic type is a glycosidic type or a phosphorylated type.
10 . The method of claim 9 , wherein the phosphorylated type is an ose-1-phosphate type.
11 . The method of claim 8 , wherein the osidic type is an ose 1 phosphate type.
12 . The method according to claim 8 , characterized in that said anchor molecule has a mass average molecular mass between 300 and 20,000.
13 . The method of claim 12 , wherein the mass average molecular mass is between 500 and 15,000.
14 . The method according to claim 12 , characterized in that said polyolefin or polyolefin oligomer or polyalkene chain comprises a number of unsaturated carbon-carbon bonds not exceeding 5%.
15 . The method of claim 14 , wherein the number of unsaturated carbon-carbon bonds does not exceed 3%.
16 . The method according to claim 14 , characterized in that said polyisobutene chain has been obtained by polymerization of a biosourced monomer.
17 . The method according to claim 16 , wherein the method is used for synthesizing oligonucleotides or oligosaccharides.
18 . The method according to claim 1 , wherein said anchor molecule comprises between 10 and 50 monomer units.