Cyclic carbamate compounds for ligation
Patent Information
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- CARBOCALYX GMBH
- Filing Date
- 2024-08-05
- Publication Date
- 2026-06-17
AI Technical Summary
Current bioconjugation techniques for linking glycans to cells or proteins face challenges such as the need for mild and selective chemistry, compatibility with aqueous solutions at low concentrations, avoidance of coupling agents and side-products, and preservation of glycan structure.
Development of cyclic carbamate compounds linked to a glycosyl moiety, along with their precursors and methods for glycosylating cells or proteins, which enable efficient and mild bioconjugation without the need for coupling agents or additives.
The proposed solution allows for the efficient and selective bioconjugation of glycans to cells or proteins, maintaining the integrity of the glycan structure and avoiding unwanted side-products, thus addressing the limitations of existing techniques.
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Abstract
Description
[0001] Cyclic Carbamate Compounds for Ligation
[0002] Field of disclosure
[0003] The present invention relates to new cyclic carbamate compounds, which are linked to a glycosyl moiety. Furthermore, the invention relates to precursors to the cyclic carbamate compounds and to methods for glycosylating a cell or a protein of interest. The invention also relates to a cell comprising a functionalized amino moiety at the cell surface and to a protein comprising a functionalized amino moiety.
[0004] Background, prior art
[0005] Glycoconjugates are important compounds in which carbohydrates of varying size and complexity are covalently bound to non-sugar moieties such as amino acids, proteins, lipids, cell membranes as well as non-biological solid surfaces (e.g. plastic or glass surfaces).
[0006] Glycoconjugates are involved in key biological processes and have found many applications as drugs and as tools for drug discovery. For instance, conjugates of carbohydrates with proteins have been utilized for the preparation of vaccines and vaccines adjuvants (F. Micoli, R. Adamo, P. Costantino, Molecules 2018, 23, 1451-1468; WO 2019 / 178699 A1 ; US 2016 / 0200758 A1). Ligation of glycans on cell-surface proteins is used for the rapid engineering of cells and the study of glycans biology in a natural environment (M. W. J. Whitehead, N. Khanzhin, L. Borsig, T. Hennet, Cell Chem. Biol. 2017, 24, 1336-1346). Furthermore, conjugation of glycans on non-biological solid surfaces is used for the preparation of glycan microarrays employed in the study of host-pathogen interactions and immune recognition (C. D. Rillahan, J. C. Paulson, Annu. Rev. Biochem. 2011 , 80, 797- 823; D. Bello-Gil, N. Khasbiullina, N. Shilova, N. Bovin, R. Manez, Front. Immunol. 2017, 8, 1449). Thus, methodologies enabling the preparation of well-defined glycoconjugates are highly important for the development of carbohydrate-based drugs, and for fundamental and clinical research.
[0007] Several bioconjugation techniques for the covalent ligation of glycans to biomolecules as well as to non-biological solid surfaces are described in the literature (F. Berti, R. Adamo, Chem. Soc. Rev. 2018, 47, 9015-9025; C. L. O'Neil, K. J. Stine, A. V. Demchenko, J Carbohydr Chem. 2018, 37, 225-249.). These techniques focus on the coupling between activated glycans and diverse reactive moieties present on the biomolecule or the solid surface. However, currently used techniques face several challenges.
[0008] For example, the chemistry applied for the ligation should be mild and selective, the ligation reaction should work in aqueous solutions and at low concentrations, no coupling agents or additives should be utilized, and no side-products should be formed. Furthermore, no immunogenic or otherwise harmful structures should result from the ligation reaction and the structure of the glycan should be preserved.
[0009] Summary of disclosure
[0010] It is therefore a general object of the present disclosure to advance the state of the art in the field of glycoconjugates. Preferably, cyclic carbamate compounds are provided which comprise a glycosyl moiety and which can be used for bioconjugation of a cell or a protein of interest with the glycosyl moiety. In further advantageous embodiments, precursors of such cyclic carbamate compounds are provided. In further advantageous embodiments, efficient and / or mild methods for glycosylating a cell or a protein of interest are provided.
[0011] The present disclosure is in a first aspect directed towards a compound of formula I: wherein
[0012] R1is H or linear or branched C1-6 alkyl;
[0013] L1 X1is selected from -O-, -S- or -NH-;
[0014] L2is a polyalkylether, alkyl or a covalent bond; m is 1 , 2, 3 or 4;
[0015] E1is selected from -O-, -S- or -NH-;
[0016] E2is selected from -CO- or -CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, -
[0017] SiR7R8R9, wherein R5is independently selected from H, Ce-w aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, Ce-w aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from Ce-w aryl and linear or branched alkyl.
[0018] In some embodiments, wherein L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or
[0019] -CH2-CH2-O-.
[0020] In some embodiments, E1is -NH- and E2is -CO-.
[0021] In some embodiments, the compound of formula I is a compound of formula la:
[0022] wherein R1is H or linear or branched C1-6 alkyl; X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl. In some embodiments, R1is H or linear C1-4alkyl, preferably H or methyl. In some embodiments, R3and R4are H. In a second aspect, the present disclosure relates to a compound of formula II: wherein R1is H or linear or branched C1-6 alkyl; L1 X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. In some embodiments, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or -CH2- CH2-O-. In some embodiments, E1is –NH- and E2is –CO-. In some embodiments, the compound of formula II is a compound of formula IIa
[0023] or branched C1-6 alkyl; , each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. In some embodiments, R1is H or linear H or C1-4alkyl, preferably H or methyl. In some embodiments, R3and R4are H. In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides, in particular between 2 and 8 glycosides, in particular between 2 and 6 glycosides. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1- 4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1-3Man-, GlcNAcb1- 6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1- 3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-. In a third aspect, the present disclosure relates to a compound of formula III: wherein R1is H or linear or branched C1-6 alkyl; L1 X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety In some embodiments, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and - CH2-CH2-O-. In some embodiments, E1is –NH- and E2is –CO-. In some embodiments, the compound of formula III is a compound of formula IIIa:
[0024] wherein R1is H or linear or branched C1-6 alkyl; L1 X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. In some embodiments, R1is H or linear C1-4alkyl, preferably H or methyl. In some embodiments, R3and R4are H. In a fourth aspect, the present disclosure relates to a method of glycosylating a cell, comprising the step of reacting a compound according to any one of the embodiments described herein, in particular with respect to the third aspect, such as the compound of formula III, IIIa, IIIb, IIIc or IIId, with an –NH2group at the cell surface to generate a glycosylated cell. In a fifth aspect, the present disclosure relates to a method of glycosylating a protein of interest, comprising the step of reacting a compound according to any one of the embodiments described herein, in particular with respect to the third aspect, such as the compound of formula III, IIIa, IIIb, IIIc or IIId, with an –NH2group of a protein of interest to generate a glycosylated protein. In a sixth aspect, the present disclosure relates to a cell comprising at least one functionalized amino moiety at the cell surface, the functionalized amino moiety having the general formula IV: wherein R1is H or linear or branched C1-6alkyl; X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. It is generally understood that the cell surface is connected at the position of the wavy bond to the functionalized amino moiety having the general formula IV, IVa, IVb, IVc, or IVd. In some embodiments, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and - CH2-CH2-O-. In some embodiments, E1is –NH- and E2is –CO-. In some embodiments, the functionalized amino moiety has the general formula IVa: wherein is H or linear or branched C1-6alkyl; L1 X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl; Y1is a glycosyl moiety In some embodiments, R1is H or linear C1-4 alkyl, preferably H or methyl. In some embodiments, R3and R4are H. In a seventh aspect, the present disclosure relates to a protein comprising at least one functionalized amino moiety, the functionalized amino moiety having the general formula V: wherein R1is H or linear or branched C1-6alkyl; L1 X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. It is generally understood that the wavy bond in formula V, Va, Vb, Vc or Vd indicates the position at which the rest of the protein is connected to functionalized amino moiety having the general formula V. In some embodiments, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and - CH2-CH2-O-. In some embodiments, E1is –NH- and E2is –CO-. In some embodiments, the functionalized amino moiety has the general formula Va: wherein R1is H or linear or branched C1-6alkyl; L1 X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl; Y1is a glycosyl moiety. In some embodiments, R1is H or linear C1-4 alkyl, preferably H or methyl. In some embodiments, R3and R4are H. In an eighth aspect, the present disclosure relates to a method of generating a compound of formula III, the method comprising the steps of: a. Reacting a compound of formula I with Y1-OH to generate a compound of formula II: b. Reacting the compound according to formula II with CO2to generate the compound of formula III: wherein R1is H or linear or branched C1-6 alkyl; X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is selected from H, C6-10 aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl; Y1is a glycosyl moiety. In some embodiments, step b. may be performed in the presence of a tertiary phosphine, e.g. a tertiary organophosphine . In some embodiments, step b. may be performed in the presence of a tertiary phosphine 20 P(R10)3: wherein preferably each R10is independently selected from alkyl or aryl. In some embodiments, each R10may be independently selected from C1-12 alkyl or C6-14 aryl. In some embodiments, step a. is performed at a pH < 7, in particular < 6. Detailed Description of the Disclosure Unless specified otherwise the following general definitions apply to all compounds of the invention according to the description. Unless specified otherwise, all general formulae and all embodiments refer in general to all possible diastereomers and all possible enantiomers. In those formulae which include stereochemical denotations such as wedged bonds, these are generally understood to refer to the relative configuration of the respective stereocenters, not their absolute configuration, such that these formulae include both enantiomers. In preferred embodiments, the stereochemical denotations in these formulae, in particular wedged bonds, may be understood to indicate the relative configuration and the absolute configuration of the respective stereocenters, such that the formulae refer to one specific enantiomer. The term "compound of the invention," as used herein, refers to compounds represented by formulae I to Vd and any of the specific examples disclosed herein. It is understood that “independently of each other” means that when a group is occurring more than one time in any compound, its definition on each occurrence is independent from any other occurrence. It is further understood that a dashed line or a wave being transverse to a bond depicts the site of attachment of a residue (i.e. a partial formula). It is also understood that a group defined as being a “covalent bond” or a “bond” refers to a direct linkage between its two neighboring groups. The same holds true if an element, such as “A”, in a formula is designated as “absent”, then the two groups linked to this element are directly connected by a bond. The term "alkyl" as used herein refers to a fully saturated branched or unbranched hydrocarbon moiety. Preferably, an alkyl may be a C1-12-alkyl, in particular a C1-6-alkyl, more preferably a C1-4-alkyl. The term "C1-6-alkyl" refers to a fully saturated branched or unbranched hydrocarbon moiety having 1, 2, 3, 4, 5 or 6 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, n-hexyl, iso-hexyl or neohexyl. Accordingly, the term "C1-4-alkyl" refers to a fully saturated branched or unbranched hydrocarbon moiety having 1, 2, 3 or 4 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl. The term “alkoxy” or “alkoxyl” as used herein refers to a fully saturated branched or unbranched alkyl moiety in which at least one hydrogen in a C-H group of the alkyl is replaced by an oxygen resulting in a C-O group and wherein the alkoxy or alkoxyl is typically bound to another moiety via the oxygen of the C-O group. Preferably, an alkyl may be a C1- 12-alkoxy, in particular a C1-6-alkoxy, more preferably a C1-4-alkoxy. Representative examples of alkoxy or alkoxyl include, but are not limited to MeO-, -CH2-O-, EtO-, -CH2- CH2-O-, n-PrO-, i-PrO-, n-BuO-, s-BuO-, t-BuO- and the like. Several if a moiety R in a formula –(R)n– is alkoxy then the alkoxy is bound to a neighboring moiety via its oxygen and to another neighboring moiety directly to one of the carbon atoms of the alkoxy by replacement of a hydrogen. For example, representative but not limiting examples of a formula –(R)2– with R being an alkoxy are for example –CH2-O-CH2CH2-O-, or –CH2-CH2- CH2-O-CH2-CH2-CH2-O-, or –CH2-CH2-O-CH2-CH2-O-. Thus, such a formula –(R)n– with R being alkoxy and n being greater than 1 result in polyalkylether moieties. A “glycosyl” or “glycosyl moiety” or “glycoside” is a univalent free radical or substituent structure obtained by removing the hemiacetal hydroxyl group from the cyclic form of a monosaccharide or an oligosaccharide. A “polyalkylether” or “polyether” is a polymer having two or more ether linkages and alkoxy repeat units. Accordingly a “poly-C1-4-alkylether” is a polyalkylether having C1-4-alkoxy repeat units. Representative but non limiting examples are polyethylene glycol or polypropylene glycol. It is understood that in the specification if a group, e.g. Y1, comprises between 2 and 6 glycosides it includes the embodiments in which it comprises exactly 2 glycosides or exactly 6 glycosides. Thus, Y1may in these embodiments for example be a disaccharide moiety. In specifications like “the A4group and the OH group adjacent to A4are both in an equatorial position” (where the A4group may for example be –N3), the OH group referred to is the OH group that is directly bonded to the carbon atom which is directly bonded to the anomeric carbon atom. In other words, the OH group referred to is the OH group that is directly bonded to the carbon atom which is directly bonded to the carbon atom which is directly bonded to the A4group. In still other words, when this specification is used to described an embodiment of general formula “example-1”, the embodiment may be represented by general formula “example-2”: This applies for example to the expressions “the –N3group and the OH group adjacent to –N3are both in an equatorial position” and “the N atom and the O atom forming the five- membered cyclic carbamate are both in an equatorial position” and “the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position”. In specifications like “the A4group and all other substituents on the hexose to which the A4group is directly bonded are in an equatorial position” (where the A4group may for example be –N3), the all other substituents referred to are all substituents that are directly bonded to the hexose. As an example, when this specification is used to describe an embodiment of general formula “example-1”, the embodiment may be represented by general formula “example-3”: This applies for example to the expressions “the –N3 group and all other substituents on the hexose to which the –N3 group is directly bonded are in an equatorial position” and “all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position” and “the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position”. It is understood that bonds indicated by a wavy line, such as those used in the structure «example-2» above, leave open the configuration of the respective stereocenter. Based on the definitions given throughout the application the skilled person knows which combinations are synthetically feasible and realistic. Thus, typically peroxide structures are preferably excluded. Compounds of formulae I, Ia, Ib, Ic and Id In a first aspect, the invention is directed to towards a compound of formula I: wherein R1is H or linear or branched C1-6 alkyl; X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or a covalent bond; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl. Typically, L1and L2do not form a –O-O-, -S-O- or –N-O- group together. An advantage of the compounds of the present disclosure is that they allow in a straightforward and divergent manner to generate large compound libraries to be connected to cells or proteins (e.g. compounds of formula III and its derivatives, such as IIIa-d). Furthermore, the Y1glycosyl moiety can be introduced and easily exchanged during the synthesis without any protecting group manipulation. By distancing the Y1group far away from the cyclic carbamate and thus the location of coupling, coupling compounds of formula III and derivatives to a cell or protein can be performed smoothly and efficiently. Furthermore, the method also allows to use 2-deoxy glcyosyl moieties. In some embodiments of the compound of formula I, R1is H or linear C1-4alkyl. In preferred embodiments, R1is H or methyl. In some embodiments of the compound of formula I, L1is –O-CH2-CO-NH- or –NH-CO-. In some embodiments of the compound of formula I, L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula I, L1is –NH-CO-. In some embodiments of the compound of formula I, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, - CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O-. In preferred embodiments, L2is –(CH2- CH2-O-)p, wherein p is 1, 2, 3 or 4. In some embodiments of the compound of formula I, E1is –NH- and E2is –CO-. In some embodiments of the compound of formula I, R3and R4are independently H or - COCH3. In preferred embodiments, R3and R4are both H. In some embodiments of the compound of formula I, the –N3group and the OH group adjacent to –N3are both in an equatorial position. In some embodiments of the compound of formula I, the –N3 group and all other substituents on the hexose to which the –N3 group is directly bonded are in an equatorial position. In the specification that “the –N3group and the OH group adjacent to –N3are both in an equatorial position”, the OH group referred to is the OH group that is directly bonded to the carbon atom which is directly bonded to the anomeric carbon atom. In other words, the OH group referred to is the OH group that is directly bonded to the carbon atom which is directly bonded to the carbon atom which is directly bonded to –N3. In some embodiments of the compound of formula I, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, - CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O- and the –N3 group and the OH group adjacent to –N3 are both in an equatorial position. In some embodiments of the compound of formula I, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O- and the –N3 group and all other substituents on the hexose to which the –N3group is directly bonded are in an equatorial position. In some embodiments of the compound of formula I, L2is –(CH2-CH2-O-)p, wherein p is 1, 2, 3 or 4 and the –N3group and the OH group adjacent to –N3are both in an equatorial position. In some embodiments of the compound of formula I, L2is –(CH2-CH2-O-)p, wherein p is 1, 2, 3 or 4 and the –N3 group and all other substituents on the hexose to which the – N3group is directly bonded are in an equatorial position. In some embodiments of the compound of formula I, E1is –NH- and E2is –CO- and R3and R4are independently H or -COCH3. In some embodiments of the compound of formula I, E1is –NH- and E2is –CO- and R3and R4are both H. In some embodiments of the compound of formula I, R1is H or linear C1-4alkyl and L1is – O-CH2-CO-NH-. In some embodiments of the compound of formula I, R1is H or methyl and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula I, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, - CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O- and the –N3group and the OH group adjacent to –N3are both in an equatorial position. In some embodiments of the compound of formula I, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the –N3group and all other substituents on the hexose to which the –N3group is directly bonded are in an equatorial position. In some embodiments of the compound of formula I, L2is –(CH2-CH2-O-)p, wherein p is 1, 2, 3 or 4 and the –N3 group and the OH group adjacent to –N3 are both in an equatorial position. In some embodiments of the compound of formula I, L2is –(CH2-CH2-O-)p, wherein p is 1, 2, 3 or 4 and the –N3group and all other substituents on the hexose to which the – N3 group is directly bonded are in an equatorial position. In some embodiments of the compound of formula I, the –N3 group and the OH group adjacent to –N3 are both in an equatorial position and R3is H and R4is H. In some embodiments of the compound of formula I, the –N3group and all other substituents on the hexose to which the –N3group is directly bonded are in an equatorial position and R3is H and R4is H. In some embodiments of the compound of formula I, L1is –O-CH2-CO-NH- and E1is –NH- and E2is –CO-. In some embodiments of the compound of formula I, E1is –NH- and E2is –CO- and R3and R4are independently H or -COCH3 and the –N3 group and the OH group adjacent to –N3 are both in an equatorial position. In some embodiments of the compound of formula I, E1is –NH- and E2is –CO- and R3and R4are both H and the –N3group and the OH group adjacent to –N3are both in an equatorial position. In some embodiments of the compound of formula I, E1is –NH- and E2is –CO- and R3and R4are independently H or -COCH3 and the –N3 group and all other substituents on the hexose to which the –N3 group is directly bonded are in an equatorial position. In some embodiments of the compound of formula I, E1is –NH- and E2is –CO- and R3and R4are both H and the –N3group and all other substituents on the hexose to which the –N3group is directly bonded are in an equatorial position. In some embodiments of the compound of formula I, R1is H or linear C1-4 alkyl and L1is – O-CH2-CO-NH- and L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O-. In some embodiments of the compound of formula I, R1is H or linear C1- 4 alkyl and L1is –O-CH2-CO-NH- and L2is –(CH2-CH2-O-)p, wherein p is 1, 2, 3 or 4. In some embodiments of the compound of formula I, R1is H or methyl and L1is –O-CH2- CO-NH- and L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula I, R1is H or methyl and L1is –O-CH2-CO-NH- and L2is –(CH2-CH2-O-)p, wherein p is 1, 2, 3 or 4. In some embodiments of the compound of formula I, R1is H or linear C1-4alkyl and L1is – O-CH2-CO-NH- and E1is –NH- and E2is –CO-. In some embodiments of the compound of formula I, R1is H or methyl and L1is –O-CH2-CO-NH- and E1is –NH- and E2is –CO-. In some embodiments of the compound of formula I, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is – O-CH2-CO-NH-. In some embodiments of the compound of formula I, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula I, R1is H or linear C1-4alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is – (L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula I, R1is H or linear C1-4 alkyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is –(CH2- CH2-O-)p, wherein p is 1, 2, 3 or 4. In some embodiments of the compound of formula I, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula I, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is –(CH2-CH2-O-)p, wherein p is 1, 2, 3 or 4. In some embodiments the compound of formula I is a compound of formula Ia, preferably Ib wherein R1is H or linear or branched C1-6alkyl; X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl. Typically, L1and L3do not form a –O-O-, -S-O- or –N-O- group together. In some embodiments of the compound of formula Ia or Ib, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl. In some embodiments of the compound of formula Ia or Ib, L1is –O-CH2-CO-NH- or –NH- CO-. In some embodiments of the compound of formula Ia or Ib, L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, L1is –NH-CO-. In some embodiments of the compound of formula Ia or Ib, n is 1, 2, 3 or 4. In some embodiments of the compound of formula Ia or Ib, L3is -CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments of the compound of formula Ia or Ib, m is 1, 2, 3 or 4, preferably 1 or 2. In some embodiments of the compound of formula Ia, R3and R4are independently H or - COCH3. In preferred embodiments, R3and R4are both H. In some embodiments of the compound of formula Ia or Ib, R1is H or linear C1-4alkyl and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, R1is H or methyl and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, R1is H or linear C1-4alkyl and n is 1, 2, 3 or 4. In some embodiments of the compound of formula Ia or Ib, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments of the compound of formula Ia or Ib, R1is H or methyl and n is 1, 2, 3 or 4. In some embodiments of the compound of formula Ia or Ib, R1is H or methyl and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments of the compound of formula Ia or Ib, n is 1, 2, 3 or 4 and L1is –O- CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, L3is -CH2-CH2- O- and n is 1, 2, 3 or 4 and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, n is 1, 2, 3 or 4 and L1is –O- CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, L3is -CH2-CH2- O- and n is 1, 2, 3 or 4 and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, n is 1, 2, 3 or 4 and R1is H or linear C1-4alkyl. In some embodiments of the compound of formula Ia or Ib, L3is -CH2-CH2- O- and n is 1, 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Ia or Ib, n is 1, 2, 3 or 4 and R1is H or methyl. In some embodiments of the compound of formula Ia or Ib, L3is -CH2-CH2-O- and n is 1, 2, 3 or 4 and R1is H or methyl. In some embodiments of the compound of formula Ia or Ib, n is 1, 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, L3is -CH2-CH2-O- and n is 1, 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, n is 1, 2, 3 or 4 and R1is H or methyl and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula Ia or Ib, L3is -CH2-CH2-O- and n is 1, 2, 3 or 4 and R1is H or methyl and L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula la or lb, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula la or lb, R1is H or methyl and L1is -O-CH2-CO-NH-.
[0025] In some embodiments of the compound of formula la or lb, R1is H or linear C1-4 alkyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula la or lb, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O- CH2-CO-NH-.
[0026] In some embodiments of the compound of formula la or lb, R1is H or methyl and n is 1 , 2,
[0027] 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula la or lb, R1is H or methyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0028] In some embodiments the compound of formula I is a compound of formula Ic , , , ,
[0029] In some embodiments of the compound of formula Ic, R1is H or methyl.
[0030] In some embodiments of the compound of formula Ic, q is 1 or 2, preferably 2.
[0031] In some embodiments of the compound of formula Ic, r is 1 , 2 or 3, preferably 1 . In some embodiments of the compound of formula Ic, q is 1 or 2 and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula Ic, q is 2 and r is 1 , 2 or 3, preferably
[0032] 1.
[0033] In some embodiments the compound of formula I is a compound of formula Id wherein q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6.
[0034] In some embodiments of the compound of formula Id, q is 1 or 2, preferably 2. In some embodiments of the compound of formula Id, r is 1 , 2 or 3, preferably 1.
[0035] In some embodiments of the compound of formula Id, q is 1 or 2 and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula Id, q is 2 and r is 1 , 2 or 3, preferably
[0036] 1.
[0037] Compounds of formulae II, Ila, lib, He and lid In a second aspect, the invention is directed to towards a compound of formula II: wherein R1is H or linear or branched C1-6 alkyl;
[0038] X1is selected from -O-, -S- or -NH-;
[0039] L2is a polyalkylether, alkyl or absent; m is 1 , 2, 3 or 4;
[0040] E1is selected from -O-, -S- or -NH-;
[0041] E2is selected from -CO- or -CH2-;
[0042] R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, Ce-w aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, Ce-w aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from Ce-w aryl and linear or branched alkyl;
[0043] Y1is a glycosyl moiety.
[0044] Typically, L1and L2do not form a -O-O-, -S-O- or -N-O- group together.
[0045] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0046] In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl. In some embodiments of the compound of formula II, L1is -O-CH2-CO-NH- or -NH-CO-. In some embodiments of the compound of formula II, L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula II, L1is -NH-CO-.
[0047] In some embodiments of the compound of formula II, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, - CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In preferred embodiments, L2is -(CH2- CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0048] In some embodiments of the compound of formula II, E1is -NH- and E2is -CO-.
[0049] In some embodiments of the compound of formula II, R3and R4are independently H or - COCH3. In preferred embodiments, R3and R4are both H.
[0050] In some embodiments of the compound of formula II, the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0051] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0052] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0053] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0054] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0055] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0056] In some embodiments of the compound of formula II, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, - CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position. In some embodiments of the compound of formula II, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0057] In some embodiments of the compound of formula II, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3. In some embodiments of the compound of formula II, E1is -NH- and E2is -CO- and R3and R4are both H.
[0058] In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and L1is - O-CH2-CO-NH-. In some embodiments of the compound of formula II, R1is H or methyl and L1is -O-CH2-CO-NH-.
[0059] In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0060] In some embodiments of the compound of formula II, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In some embodiments of the compound of formula II, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0061] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0062] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is
[0063] 1 , 2, 3 or 4 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and all other substituents on the hexose to which the - N3 group is directly bonded are in an equatorial position.
[0064] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0065] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 ,
[0066] 2, 3 or 4 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and all other substituents on the hexose to which the - N3 group is directly bonded are in an equatorial position. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position and R3is H and R4is H. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position and R3is H and R4is H.
[0067] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position and R3is H and R4is H. In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position and R3is H and R4is H.
[0068] In some embodiments of the compound of formula II, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH- and E1is - NH- and E2is -CO-. In some embodiments of the compound of formula II, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2- CO-NH- and E1is -NH- and E2is -CO-.
[0069] In some embodiments of the compound of formula II, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments of the compound of formula II, E1is -NH- and E2is -CO- and R3and R4are both H and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position.
[0070] In some embodiments of the compound of formula II, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3 and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position. In some embodiments of the compound of formula II, E1is -NH- and E2is -CO- and R3and R4are both H and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0071] In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and L1is - O-CH2-CO-NH- and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula II, R1is H or linear C1- 4 alkyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0072] In some embodiments of the compound of formula II, R1is H or methyl and L1is -O-CH2- CO-NH- and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula II, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0073] In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and L1is - O-CH2-CO-NH- and E1is -NH- and E2is -CO-. In some embodiments of the compound of formula II, R1is H or methyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0074] In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is - O-CH2-CO-NH-. In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0075] In some embodiments of the compound of formula II, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2- CO-NH-. In some embodiments of the compound of formula II, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is - O-CH2-CO-NH-. In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is - (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2- CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0076] In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula II, R1is H or linear C1-4 alkyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides L2is -(CH2-CH2- O-)p, wherein p is 1 , 2, 3 or 4.
[0077] In some embodiments of the compound of formula II, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula II, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0078] In some embodiments of the compound of formula II, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula II, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4. In some embodiments the compound of formula II is a compound of formula Ila, preferably lib wherein R1is H or linear or branched C1-6 alkyl;
[0079] X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- or - CH2-CH2-O-; n is 1 , 2, 3, 4, 5, 6, 7 or 8; m is 1 , 2, 3 or 4;
[0080] R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, Ce-w aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, Ce-w aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from Ce-w aryl and linear or branched alkyl;
[0081] Y1is a glycosyl moiety. Typically, L1and L3do not form a -O-O-, -S-O- or -N-O- group together.
[0082] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0083] In some embodiments of the compound of formula Ila or lib, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl.
[0084] In some embodiments of the compound of formula Ila or lib, L1is -O-CH2-CO-NH- or -NH- CO-. In some embodiments of the compound of formula Ila or lib, L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, L1is -NH-CO-.
[0085] In some embodiments of the compound of formula Ila or lib, n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Ila or lib, L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0086] In some embodiments of the compound of formula Ila or lib, m is 1 , 2, 3 or 4, preferably 1 or 2.
[0087] In some embodiments of the compound of formula Ila, R3and R4are independently H or - COCH3. In preferred embodiments, R3and R4are both H.
[0088] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0089] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or
[0090] 4.
[0091] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0092] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or methyl.
[0093] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or methyl.
[0094] In some embodiments of the compound of formula Ila or lib, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, R1is H or methyl and L1is -O-CH2-CO-NH-.
[0095] In some embodiments of the compound of formula Ila or lib, R1is H or linear C1-4 alkyl and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Ila or lib, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0096] In some embodiments of the compound of formula Ila or lib, R1is H or methyl and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Ila or lib, R1is H or methyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Ila or lib, n is 1, 2, 3 or 4 and L1is -O- CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, L3is -CH2-CH2- O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0097] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and L1is -O- CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2- CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0098] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and L1is -O- CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2- O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0099] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Ila or lib, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2- CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl.
[0100] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Ila or lib, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2- O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl.
[0101] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl.
[0102] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl.
[0103] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-.
[0104] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-.
[0105] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0106] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0107] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0108] In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0109] In some embodiments of the compound of formula Ila or lib, R1is H or linear C1-4 alkyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0110] In some embodiments of the compound of formula Ila or lib, R1is H or methyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Ila or lib, R1is H or methyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0111] In some embodiments the compound of formula II is a compound of formula lie lie OH wherein
[0112] R1is H or C1-4 alkyl; q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6;
[0113] Y1is a glycosyl moiety.
[0114] In some embodiments of the compound of formula He, R1is H or methyl.
[0115] In some embodiments of the compound of formula He, q is 1 or 2, preferably 2.
[0116] In some embodiments of the compound of formula He, r is 1 , 2 or 3, preferably 1.
[0117] In some embodiments of the compound of formula He, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0118] In some embodiments of the compound of formula He, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula He, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1.
[0119] In some embodiments of the compound of formula He, q is 1 or 2 and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula He, q is 2 and r is 1 , 2 or 3, preferably 1.
[0120] In some embodiments of the compound of formula He, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula He, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2.
[0121] In some embodiments of the compound of formula He, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1 , 2 or 3. In some embodiments of the compound of formula IIc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments the compound of formula II is a compound of formula IId , , , , is a glycosyl moiety. In some embodiments of the compound of formula IId, q is 1 or 2, preferably 2. In some embodiments of the compound of formula IId, r is 1, 2 or 3, preferably 1. In some embodiments of the compound of formula IId, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides. In some embodiments of the compound of formula IId, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and r is 1, 2 or 3, preferably 1. In some embodiments of the compound of formula IId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1, 2 or 3, preferably 1. In some embodiments of the compound of formula IId, q is 1 or 2 and r is 1, 2 or 3, preferably 1. In some embodiments of the compound of formula IId, q is 2 and r is 1, 2 or 3, preferably 1. In some embodiments of the compound of formula IId, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula IId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula IId, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments of the compound of formula IId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments of the compound of formulae II, IIa, IIb, IIc or IId, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1- 3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6-Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1- 4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2- 3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1- 3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1- 3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2- 4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1- 4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1- 3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2- Galβ1-4GlcNAc-, GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1- 3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1- 3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1- 3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc- and GlcNAcβ1-2Galβ1-3- GalNAc. In some embodiments of the compound of formulae II, IIa, IIb, IIc or IId, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1- 3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6-Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1- 4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2- 3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1- 3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1- 3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2- 4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1- 4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1- 3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2- Galβ1-4GlcNAc-, GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1- 3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1- 3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1- 3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1- 4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1- 3Man-, GlcNAcb1-6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1- 4Glc-, GalNAcb1-3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1- 3Gal-. In some preferred embodiments of the compound of formulae II, IIa, IIb, IIc or IId, Y1is selected from Rha-, ManNAc-, GlcNAc-, GalNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, Galβ1-3GlcNAcα1- 6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, Fucα1-2Galβ1- 4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Galβ1-3GlcNAcβ1-3Galβ1- 4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, GlcNAcβ1-3GalNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, Galβ1-4GlcNAcβ1- 6GalNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. Compounds of formulae III, IIIa, IIIb, IIIc and IIId In a third aspect, the invention is directed to towards a compound of formula III: wherein R1is H or linear or branched C1-6 alkyl; L1 X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. Typically, L1and L2do not form a –O-O-, -S-O- or –N-O- group together. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides. In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl. In some embodiments of the compound of formula III, L1is –O-CH2-CO-NH- or –NH-CO-. In some embodiments of the compound of formula III, L1is –O-CH2-CO-NH-. In some embodiments of the compound of formula III, L1is –NH-CO-. In some embodiments of the compound of formula III, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In preferred embodiments, L2is – (CH2-CH2-O-)p, wherein p is 1, 2, 3 or 4. In some embodiments of the compound of formula III, E1is –NH- and E2is –CO-. In some embodiments of the compound of formula III, R3and R4are independently H or - COCH3. In preferred embodiments, R3and R4are both H. In some embodiments of the compound of formula III, the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0122] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0123] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0124] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0125] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0126] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0127] In some embodiments of the compound of formula III, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, - O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0128] In some embodiments of the compound of formula III, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, L2is — (CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0129] In some embodiments of the compound of formula III, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCHs. In some embodiments of the compound of formula III, E1is -NH- and E2is -CO- and R3and R4are both H.
[0130] In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and L1is - O-CH2-CO-NH-. In some embodiments of the compound of formula III, R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0131] In some embodiments of the compound of formula III, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In some embodiments of the compound of formula III, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0132] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, - O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0133] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0134] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O- CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0135] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is - (CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0136] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position and R3is H and R4is H. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position and R3is H and R4is H.
[0137] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position and R3is H and R4is H. In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position and R3is H and R4is H.
[0138] In some embodiments of the compound of formula III, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH- and E1is - NH- and E2is -CO-. In some embodiments of the compound of formula III, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2- CO-NH- and E1is -NH- and E2is -CO-.
[0139] In some embodiments of the compound of formula III, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3 and the N atom and the O atom forming the five- membered cyclic carbamate are both in an equatorial position. In some embodiments of the compound of formula III, E1is -NH- and E2is -CO- and R3and R4are both H and the N atom and the O atom forming the five-membered cyclic carbamate are both in an equatorial position.
[0140] In some embodiments of the compound of formula III, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3 and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position. In some embodiments of the compound of formula III, E1is -NH- and E2is -CO- and R3and R4are both H and all substituents on the hexose that is fused to the five-membered cyclic carbamate are in an equatorial position.
[0141] In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and L1is - O-CH2-CO-NH- and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0142] In some embodiments of the compound of formula III, R1is H or methyl and L1is -O-CH2- CO-NH- and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula III, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0143] In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and L1is - O-CH2-CO-NH- and E1is -NH- and E2is -CO-. In some embodiments of the compound of formula III, R1is H or methyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0144] In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is - O-CH2-CO-NH-. In some embodiments of the compound of formula III, R1is H or linear C1- 4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0145] In some embodiments of the compound of formula III, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2- CO-NH-. In some embodiments of the compound of formula III, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is - O-CH2-CO-NH-.
[0146] In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is - (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2- CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0147] In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula III, R1is H or linear C1-4 alkyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides L2is -(CH2-CH2- O-)p, wherein p is 1 , 2, 3 or 4.
[0148] In some embodiments of the compound of formula III, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula III, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0149] In some embodiments of the compound of formula III, R1is H or methyl and Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments of the compound of formula III, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0150] In some embodiments the compound of formula III is a compound of formula Illa, preferably lllb wherein R1is H or linear or branched C1-6alkyl; X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl; Y1is a glycosyl moiety. Typically, L1and L3do not form a –O-O-, -S-O- or –N-O- group together. In some embodiments of the compound of formula IIIa or IIIb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides. In some embodiments of the compound of formula IIIa or IIIb, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl. In some embodiments of the compound of formula Illa or I lib, L1is -O-CH2-CO-NH- or - NH-CO-. In some embodiments of the compound of formula Illa or II lb, L1is -O-CH2-CO- NH-. In some embodiments of the compound of formula Illa or lllb, L1is -NH-CO-.
[0151] In some embodiments of the compound of formula Illa or lllb, n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Illa or lllb, L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0152] In some embodiments of the compound of formula Illa or lllb, m is 1 , 2, 3 or 4, preferably 1 or 2.
[0153] In some embodiments of the compound of formula Illa, R3and R4are independently H or - COCH3. In preferred embodiments, R3and R4are both H.
[0154] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0155] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0156] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or lllb, Y1is mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Illa or I lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or methyl.
[0157] In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Illa or I lib, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or methyl.
[0158] In some embodiments of the compound of formula Illa or 111 b, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or 111 b, R1is H or methyl and L1is -O-CH2-CO-NH-.
[0159] In some embodiments of the compound of formula Illa or 111 b, R1is H or linear C1-4 alkyl and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Illa or 111 b, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0160] In some embodiments of the compound of formula Illa or 111 b, R1is H or methyl and n is 1 , 2, 3 or 4. In some embodiments of the compound of formula Illa or 11 lb, R1is H or methyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0161] In some embodiments of the compound of formula Illa or lllb, n is 1 , 2, 3 or 4 and L1is -O- CH2-CO-NH-. In some embodiments of the compound of formula Illa or lllb, L3is -CH2-CH2- O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0162] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and L1is -O- CH2-CO-NH-. In some embodiments of the compound of formula Illa or lllb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2- CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and L1is -O- CH2-CO-NH-. In some embodiments of the compound of formula Illa or lllb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2- O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0163] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Illa or lllb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2- CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl.
[0164] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments of the compound of formula Illa or lllb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2- O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl.
[0165] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments of the compound of formula Illa or lllb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2- CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl.
[0166] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments of the compound of formula Illa or lllb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2- O- and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-.
[0167] In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-.
[0168] In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O- CH2-CO-NH-.
[0169] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0170] In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or lllb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0171] In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or 111 b, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0172] In some embodiments of the compound of formula Illa or 111 b, R1is H or linear C1-4 alkyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or 11 lb, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0173] In some embodiments of the compound of formula Illa or 111 b, R1is H or methyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula Illa or 11 lb, R1is H or methyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO- NH-.
[0174] In some embodiments the compound of formula III is a compound of formula lllc wherein
[0175] R1is H or C1-4 alkyl; q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6;
[0176] Y1is a glycosyl moiety. In some embodiments of the compound of formula lllc, R1is H or methyl.
[0177] In some embodiments of the compound of formula lllc, q is 1 or 2, preferably 2.
[0178] In some embodiments of the compound of formula lllc, r is 1 , 2 or 3, preferably 1.
[0179] In some embodiments of the compound of formula lllc, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0180] In some embodiments of the compound of formula lllc, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula lllc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1.
[0181] In some embodiments of the compound of formula lllc, q is 1 or 2 and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula lllc, q is 2 and r is 1 , 2 or 3, preferably 1.
[0182] In some embodiments of the compound of formula lllc, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula lllc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2.
[0183] In some embodiments of the compound of formula lllc, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1 , 2 or 3. In some embodiments of the compound of formula lllc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1 , 2 or 3.
[0184] In some embodiments the compound of formula III is a compound of formula Hid wherein q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6;
[0185] Y1is a glycosyl moiety.
[0186] In some embodiments of the compound of formula Hid, q is 1 or 2, preferably 2.
[0187] In some embodiments of the compound of formula Hid, r is 1 , 2 or 3, preferably 1.
[0188] In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0189] In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1.
[0190] In some embodiments of the compound of formula Hid, q is 1 or 2 and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula Hid, q is 2 and r is 1 , 2 or 3, preferably 1 .
[0191] In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments of the compound of formulae III, IIIa, IIIb, IIIc or IIId, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1- 3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, GalNAcα1- 3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6-Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1- 4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1- 4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2- 8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1- 3Galα1-4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1- 3Galβ1-3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1- 3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1- 3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc- and GlcNAcβ1-2Galβ1-3- GalNAc. In some embodiments of the compound of formulae III, IIIa, IIIb, IIIc or IIId, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1- 3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, GalNAcα1- 3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6-Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1- 4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1- 4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2- 8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1- 3Galα1-4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1- 3Galβ1-3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1- 3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1- 3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1- 4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1- 3Man-, GlcNAcb1-6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1- 4Glc-, GalNAcb1-3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1- 3Gal-. In some preferred embodiments of the compound of formulae III, IIIa, IIIb, IIIc or IIId, Y1is selected from Rha-, ManNAc-, GlcNAc-, GalNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, Galβ1-3GlcNAcα1- 6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, Fucα1-2Galβ1- 4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Galβ1-3GlcNAcβ1-3Galβ1- 4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, GlcNAcβ1-3GalNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, Galβ1-4GlcNAcβ1- 6GalNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. Method for glycosylating a cell
[0192] In a fourth aspect, the invention relates to a method for glycosylating a cell, comprising the steps of reacting a compound according to any of the embodiments as described herein, in particular with respect to the third aspect, such as the compound of formula III according to any of the embodiments as described herein, in particular with respect to the third aspect, with an -NH2 group at the cell surface of a cell to generate a glycosylated cell.
[0193] In some embodiments, the method for glycosylating a cell comprises incubation of the cell with the compound of formula III.
[0194] In some embodiments, the method for glycosylating a cell, and in particular the incubation, is performed at temperatures of between 0 °C and 37 °C, preferably between 0 °C and 25 °C, more preferably between 0 °C and 10 °C.
[0195] In some embodiments, the method for glycosylating a cell, and in particular the incubation, is performed at pH 7 to 8, in particular at pH 7.2 and 7.5.
[0196] In some embodiments, the method for glycosylating a cell, and in particular the incubation, is performed by using an aqueous buffer solution, such as PBS, as the solvent.
[0197] In some embodiments the method for glycosylating a cell comprises the steps of reacting a compound of formula III, Illa, lllb, lllc or Hid according to any of the embodiments as described herein, in particular with respect to the third aspect, with an -NH2 group at the cell surface to generate a glycosylated cell.
[0198] Method for glycosylating a protein of interest
[0199] In a fifth aspect, the invention relates to a method for glycosylating a protein of interest, comprising the steps of reacting a compound according to any of the embodiments as described herein, in particular with respect to the first aspect, such as the compound of formula III, Illa, lllb, lllc or Hid according to any of the embodiments as described herein, in particular with respect to the third aspect, with an -NH2 group of a protein of interest to generate a glycosylated protein.
[0200] In some embodiments, the method for glycosylating a protein of interest comprises incubation of the protein of interest with the compound of formula III.
[0201] In some embodiments, the method for glycosylating a protein of interest, and in particular the incubation, is performed at temperatures of between 0 °C and 40 °C, preferably between 20 °C and 38 °C, more preferably between 30 °C and 37 °C.
[0202] In some embodiments, the method for glycosylating a protein of interest, and in particular the incubation, is performed at pH 7 to 10, preferably at pH 7 to 8, more preferably at pH 7.2 and 7.5.
[0203] In some embodiments, the method for glycosylating a protein of interest, and in particular the incubation, is performed by using an aqueous buffer solution, such as PBS, as the solvent.
[0204] In some embodiments the method for glycosylating a protein of interest comprises the steps of reacting a compound of formula III, Illa, lllb, lllc or Hid according to any of the embodiments as described herein, in particular with respect to the first aspect, with an -NH2 group of a protein of interest to generate a glycosylated protein.
[0205] Cell with a functionalized amino moiety
[0206] In a sixth aspect, the invention relates to a cell comprising at least one functionalized amino moiety at the cell surface, the functionalized amino moiety having the general formula IV: wherein R1is H or linear or branched C1-6alkyl; L1 X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. Typically, L1and L2do not form a –O-O-, -S-O- or –N-O- group together. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0207] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl.
[0208] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, L1is -O-CH2-CO-NH- or -NH-CO-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, L1is -NH-CO-.
[0209] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O-. In preferred embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0210] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, E1is -NH- and E2is -CO-.
[0211] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R3and R4are independently H or -COCH3. In preferred embodiments, R3and R4are both H.
[0212] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position. It is understood that that “urea- forming N atom” refers to that N atom of the urea moiety which is directly bonded to the anomeric carbon atom of the hexose. Thus, the OH group adjacent to that N atom is the OH group that is directly bonded to the carbon atom which is directly bonded to the anomeric carbon atom.
[0213] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0214] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0215] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0216] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0217] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0218] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O- and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0219] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0220] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, E1is - NH- and E2is -CO- and R3and R4are both H.
[0221] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and L1is - O-CH2-CO-NH-.
[0222] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0223] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0224] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O- and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2- O-CH2- and -CH2-CH2-O- and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0225] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O- and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0226] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position and R3is H and R4is H. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position and R3is H and R4is H.
[0227] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position and R3is H and R4is H. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position and R3is H and R4is H.
[0228] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0229] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3 and the urea- forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, E1is -NH- and E2is -CO- and R3and R4are both H and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3 and the urea- forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, E1is -NH- and E2is -CO- and R3and R4are both H and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0230] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0231] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0232] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0233] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0234] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0235] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0236] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, - CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0237] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0238] In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety at the cell surface of formula IV, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0239] In some embodiments the functionalized amino moiety at the cell surface of formula IV is of general formula IVa, preferably IVb: wherein
[0240] R1is H or linear or branched C1-6 alkyl;
[0241] X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1 , 2, 3, 4, 5, 6, 7 or 8; m is 1 , 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. Typically, L1and L3do not form a –O-O-, -S-O- or –N-O- group together. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, L1is –O-CH2-CO-NH- or –NH-CO-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, L1is –NH-CO-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, L3is -CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, m is 1, 2, 3 or 4, preferably 1 or 2. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa, R3and R4are independently H or -COCH3. In preferred embodiments, R3and R4are both H. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or linear C1-4alkyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or methyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or linear C1-4alkyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or methyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or linear C1-4alkyl and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or methyl and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or linear C1-4alkyl and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or methyl and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or methyl and L3is -CH2-CH2- O- and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, n is 1, 2, 3 or 4 and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, L3is -CH2-CH2-O- and n is 1, 2, 3 or 4 and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1, 2, 3 or 4 and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4 and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1, 2, 3 or 4 and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4 and L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1, 2, 3 or 4 and R1is H or linear C1-4alkyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4 and R1is H or linear C1-4alkyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1, 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1, 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1, 2, 3 or 4 and R1is H or methyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl.
[0242] In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl.
[0243] In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2- CO-NH-.
[0244] In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO- NH-.
[0245] In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0246] In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2- O- and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0247] In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0248] In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or linear CM alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0249] In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or linear C1-4 alkyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-
[0250] NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or methyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety at the cell surface of formula IVa or IVb, R1is H or methyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0251] In some embodiments the functionalized amino moiety at the cell surface of formula IV is of general formula IVc: wherein
[0252] R1is H or C1-4 alkyl; q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6;
[0253] Y1is a glycosyl moiety.
[0254] In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, R1is H or methyl.
[0255] In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, q is 1 or 2, preferably 2.
[0256] In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, r is 1 , 2 or 3, preferably 1.
[0257] In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0258] In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1.
[0259] In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, q is 1 or 2 and r is 1 , 2 or 3, preferably 1 . In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, q is 2 and r is 1 , 2 or 3, preferably 1 .
[0260] In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2.
[0261] In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1 , 2 or 3. In some embodiments in the functionalized amino moiety at the cell surface of formula IVc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1 , 2 or 3.
[0262] In some embodiments the functionalized amino moiety at the cell surface of formula IV is of general formula IVd: wherein q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6;
[0263] Y1is a glycosyl moiety.
[0264] In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, q is 1 or 2, preferably 2.
[0265] In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, r is 1 , 2 or 3, preferably 1.
[0266] In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0267] In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1.
[0268] In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, q is 1 or 2 and r is 1 , 2 or 3, preferably 1 . In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, q is 2 and r is 1 , 2 or 3, preferably 1 . In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2. In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments in the functionalized amino moiety at the cell surface of formula IVd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments in the functionalized amino moiety at the cell surface of formulae IV, IVa, IVb, IVc, IVd, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments in the functionalized amino moiety at the cell surface of formulae IV, IVa, IVb, IVc, IVd, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1- 4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1-3Man-, GlcNAcb1- 6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1- 3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-. In preferred embodiments in the functionalized amino moiety at the cell surface of formulae IV, IVa, IVb, IVc, IVd, Y1is selected from Rha-, ManNAc-, GlcNAc-, GalNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1- 4GlcNAc-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, GlcNAcβ1-3GalNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, Galβ1-4GlcNAcβ1-6GalNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. Protein with a functionalized amino moiety In a seventh aspect, the invention relates to a protein comprising at least one functionalized amino moiety, the functionalized amino moiety having the general formula V wherein R1is H or linear or branched C1-6alkyl; X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. Typically, L1and L2do not form a -O-O-, -S-O- or -N-O- group together.
[0269] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides. In some embodiments in the functionalized amino moiety of formula V, R1is H or linear Ci- 4 alkyl. In preferred embodiments, R1is H or methyl.
[0270] In some embodiments in the functionalized amino moiety of formula V, L1is -O-CH2-CO- NH- or -NH-CO-. In some embodiments in the functionalized amino moiety of formula V, L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula V, L1is -NH-CO-.
[0271] In some embodiments in the functionalized amino moiety of formula V, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In preferred embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula V, E1is -NH- and E2is -CO-.
[0272] In some embodiments in the functionalized amino moiety of formula V, R3and R4are independently H or -COCHs. In preferred embodiments, R3and R4are both H.
[0273] In some embodiments in the functionalized amino moiety of formula V, the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position. It is understood that that “urea-forming N atom” refers to that N atom of the urea moiety which is directly bonded to the anomeric carbon atom of the hexose. Thus, the OH group adjacent to that N atom is the OH group that is directly bonded to the carbon atom which is directly bonded to the anomeric carbon atom.
[0274] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0275] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the urea- forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the urea- forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0276] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the urea- forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the urea- forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0277] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2- CO-NH-. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O- CH2-CO-NH-.
[0278] In some embodiments in the functionalized amino moiety of formula V, L2is - (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, L2is -(CH2-CH2- O-)p, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea- forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0279] In some embodiments in the functionalized amino moiety of formula V, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3. In some embodiments in the functionalized amino moiety of formula V, E1is -NH- and E2is -CO- and R3and R4are both H.
[0280] In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1- 4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and L1is -O-CH2-CO-NH-.
[0281] In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1- 4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0282] In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0283] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is - (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0284] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2- CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0285] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is - (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0286] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2- CH2-0-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0287] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the urea- forming N atom and the OH group adjacent to that N atom are both in an equatorial position and R3is H and R4is H. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position and R3is H and R4is H.
[0288] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the urea- forming N atom and the OH group adjacent to that N atom are both in an equatorial position and R3is H and R4is H. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position and R3is H and R4is H.
[0289] In some embodiments in the functionalized amino moiety of formula V, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2- CO-NH- and E1is -NH- and E2is -CO-. In some embodiments in the functionalized amino moiety of formula V, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0290] In some embodiments in the functionalized amino moiety of formula V, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3 and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, E1is -NH- and E2is -CO- and R3and R4are both H and the urea-forming N atom and the OH group adjacent to that N atom are both in an equatorial position.
[0291] In some embodiments in the functionalized amino moiety of formula V, E1is -NH- and E2is -CO- and R3and R4are independently H or -COCH3 and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position. In some embodiments in the functionalized amino moiety of formula V, E1is -NH- and E2is -CO- and R3and R4are both H and the urea-forming N atom and all other substituents on the hexose to which that N atom is directly bonded are in an equatorial position.
[0292] In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1- 4 alkyl and L1is -O-CH2-CO-NH- and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0293] In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, - CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0294] In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1- 4 alkyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-. In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-. In some embodiments in the functionalized amino moiety of formula V, R1is H or linear Ci- 4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0295] In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is -O-CH2-CO-NH-.
[0296] In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1- 4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0297] In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1- 4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O-. In some embodiments in the functionalized amino moiety of formula V, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0298] In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O-. In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0299] In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2- CH2-O-. In some embodiments in the functionalized amino moiety of formula V, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0300] In some embodiments the functionalized amino moiety of formula V is of general formula
[0301] Va, preferably Vb: wherein
[0302] R1is H or linear or branched C1-6 alkyl;
[0303] X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1 , 2, 3, 4, 5, 6, 7 or 8; m is 1 , 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. Typically, L1and L3do not form a –O-O-, -S-O- or –N-O- group together. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides. In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl. In some embodiments in the functionalized amino moiety of formula Va or Vb, L1is –O-CH2- CO-NH- or –NH-CO-. In some embodiments in the functionalized amino moiety of formula Va or Vb, L1is –O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, L1is –NH-CO-. In some embodiments in the functionalized amino moiety of formula Va or Vb, n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula Va or Vb, L3is - CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula Va or Vb, m is 1, 2, 3 or 4, preferably 1 or 2. In some embodiments in the functionalized amino moiety of formula Va, R3and R4are independently H or -COCH3. In preferred embodiments, R3and R4are both H. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is - CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is - CH2-CH2-O- and n is 1, 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is –O-CH2- CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L1is – O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or linear C1-4 alkyl. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or methyl.
[0304] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or linear C1-4 alkyl. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or methyl.
[0305] In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or methyl and L1is -O-CH2-CO-NH-.
[0306] In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or linear C1-4 alkyl and n is 1 , 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or linear C1-4 alkyl and L3is -CH2-CH2-O- and n is 1 , 2,
[0307] 3 or 4.
[0308] In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or methyl and n is 1 , 2, 3 or 4. In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or methyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4.
[0309] In some embodiments in the functionalized amino moiety of formula Va or Vb, n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0310] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or
[0311] 4 and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0312] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl.
[0313] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl.
[0314] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl.
[0315] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-.
[0316] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or linear C14 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-.
[0317] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0318] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0319] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0320] In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and R1is H or methyl and L1is -O-CH2-CO-NH-.
[0321] In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or linear C1-4 alkyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or linear C1-4 alkyl and L3is -CH2- CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0322] In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or methyl and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-. In some embodiments in the functionalized amino moiety of formula Va or Vb, R1is H or methyl and L3is -CH2-CH2-O- and n is 1 , 2, 3 or 4 and L1is -O-CH2-CO-NH-.
[0323] In some embodiments the functionalized amino moiety of formula V is of general formula Vc: wherein
[0324] R1is H or C1-4 alkyl; q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6; Y1is a glycosyl moiety.
[0325] In some embodiments in the functionalized amino moiety of formula Vc, R1is H or methyl.
[0326] In some embodiments in the functionalized amino moiety of formula Vc, q is 1 or 2, preferably 2.
[0327] In some embodiments in the functionalized amino moiety of formula Vc, r is 1 , 2 or 3, preferably 1.
[0328] In some embodiments in the functionalized amino moiety of formula Vc, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0329] In some embodiments in the functionalized amino moiety of formula Vc, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments in the functionalized amino moiety of formula Vc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1.
[0330] In some embodiments in the functionalized amino moiety of formula Vc, q is 1 or 2 and r is 1 , 2 or 3, preferably 1. In some embodiments in the functionalized amino moiety of formula Vc, q is 2 and r is 1 , 2 or 3, preferably 1.
[0331] In some embodiments in the functionalized amino moiety of formula Vc, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments in the functionalized amino moiety of formula Vc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2. In some embodiments in the functionalized amino moiety of formula Vc, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1 , 2 or 3. In some embodiments in the functionalized amino moiety of formula Vc, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1 , 2 or 3.
[0332] In some embodiments the functionalized amino moiety of formula V is of general formula Vd: wherein q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6;
[0333] Y1is a glycosyl moiety.
[0334] In some embodiments in the functionalized amino moiety of formula Vd, q is 1 or 2, preferably 2.
[0335] In some embodiments in the functionalized amino moiety of formula Vd, r is 1 , 2 or 3, preferably 1 .
[0336] In some embodiments in the functionalized amino moiety of formula Vd, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0337] In some embodiments in the functionalized amino moiety of formula Vd, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments in the functionalized amino moiety of formula Vd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1, 2 or 3, preferably 1. In some embodiments in the functionalized amino moiety of formula Vd, q is 1 or 2 and r is 1, 2 or 3, preferably 1. In some embodiments in the functionalized amino moiety of formula Vd, q is 2 and r is 1, 2 or 3, preferably 1. In some embodiments in the functionalized amino moiety of formula Vd, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments in the functionalized amino moiety of formula Vd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2. In some embodiments in the functionalized amino moiety of formula Vd, Y1is a mono- glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments in the functionalized amino moiety of formula Vd, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments in the functionalized amino moiety of formulae V, Va, Vb, Vc or Vd, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1- 3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1-3GlcNAcα1- 6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6-Bn-Galα1- 4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1- 4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2- 8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1- 5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su- GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1- 4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1- 4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1- 3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1- 4Galβ1-4GlcNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments in the functionalized amino moiety of formulae V, Va, Vb, Vc or Vd, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1- 3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1-3GlcNAcα1- 6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6-Bn-Galα1- 4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1- 4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2- 8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1- 5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su- GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1- 4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1- 4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1- 3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1- 4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1-4GlcNAc-, GlcNAcb1- 4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1-3Man-, GlcNAcb1-6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1-3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-. In preferred embodiments in the functionalized amino moiety of formulae V, Va, Vb, Vc or Vd, Y1is selected from Rha-, ManNAc-, GlcNAc-, GalNAc-, Galβ1-4Glc-, Galβ1-6Galβ1- 4Glc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Galβ1- 3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1- 3Galβ1-4Glc-, GlcNAcβ1-3GalNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, Galβ1- 4GlcNAcβ1-6GalNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. Method of generating a compound of formula III In an eight aspect, the invention relates to a method of generating a compound of formula III, the method comprising the steps of: a. Reacting a compound of formula I with Y1-OH to generate a compound of formula II: b. Reacting the compound according to formula II with CO2 to generate the compound of formula III: wherein R1is H or linear or branched C1-6 alkyl; X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety. Typically, L1and L2do not form a –O-O-, -S-O- or –N-O- group together. In some embodiments, step b. may be performed in the presence of a catalyst, such as a transition metal catalyst, and / or in the presence of a Lewis base, such as an organophosphine, e.g. a tertiary phosphine. In some embodiments, step b. may be performed in the presence of a tertiary phosphine, e.g. a tertiary organophosphine . In some embodiments, step b. may be performed in the presence of a tertiary phosphine P(R10)3: wherein preferably each R10is independently selected from alkyl or aryl. In some embodiments, each R10may be independently selected from C1-12alkyl or C6-14aryl, in particular C1-8alkyl or C6-C10aryl. In some embodiments, step b. is performed at about 15 °C to about 35 °C, in particular at about 15 °C to about 30 °C, more particular at about 15 °C to about 25 °C. In some embodiments, step b is performed under a CO2atmosphere at a pressure of 1 bar. or more, in particular at a CO2pressure of about 1 bar. to about 50 bar, more particular of about 2 bar to about 20 bar, even more particular of about 4 bar. to about 10 bar. In some embodiments, step b. is performed in a polar solvent, such as DMF, DMSO, water or mixtures thereof, in particular DMF. In some embodiments, step a. is performed at a pH < 7, in particular < 6. In some embodiments step a. is performed at of about pH 3 to about pH 6, in particular of about pH 4 to about pH 6, more particular of about pH 4.5 to about pH 5.5. In some embodiments, step a. may comprise the addition of an acid, in particular a Bronsted acid. In some embodiments, step a. may comprise the addition of HCI, HNO3 or H2SO4, in particular HCI. In some embodiments, step a. may comprise the addition of an acetate salt, such as NH4OAC, NaOAc, LiOAc or the like. In some embodiments, step a. may comprise the addition of an acid.
[0338] In some embodiments, R1is H or linear C1-4 alkyl. In preferred embodiments, R1is H or methyl.
[0339] In some embodiments, L1is -O-CH2-CO-NH- or -NH-CO-. In some embodiments of the compound of formula I, L1is -O-CH2-CO-NH-. In some embodiments of the compound of formula I, L1is -NH-CO-.
[0340] In some embodiments, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2- O-CH2-, and -CH2-CH2-O-. In preferred embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0341] In some embodiments, E1is -NH- and E2is -CO-.
[0342] In some embodiments, R3and R4are independently H or -COCH3. In preferred embodiments, R3and R4are both H.
[0343] In some embodiments, the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0344] In the specification that “the -N3 group and the OH group adjacent to -N3 are both in an equatorial position”, the OH group referred to is the OH group that is directly bonded to the carbon atom which is directly bonded to the anomeric carbon atom. In other words, the OH group referred to is the OH group that is directly bonded to the carbon atom which is directly bonded to the carbon atom which is directly bonded to -N3. In some embodiments, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2- O-CH2-, and -CH2-CH2-O- and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, - O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O- and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0345] In some embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0346] In some embodiments, E1is -NH- and E2is -CO- and R3and R4are independently H or - COCH3. In some embodiments, E1is -NH- and E2is -CO- and R3and R4are both H.
[0347] In some embodiments, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments, R1is H or methyl and L1is -O-CH2-CO-NH-.
[0348] In some embodiments, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2- O-CH2-, and -CH2-CH2-O- and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, - O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0349] In some embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position. In some embodiments, the -N3 group and the OH group adjacent to -N3 are both in an equatorial position and R3is H and R4is H. In some embodiments, the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position and R3is H and R4is H.
[0350] In some embodiments, L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0351] In some embodiments, E1is -NH- and E2is -CO- and R3and R4are independently H or - COCH3 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, E1is -NH- and E2is -CO- and R3and R4are both H and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position.
[0352] In some embodiments, E1is -NH- and E2is -CO- and R3and R4are independently H or - COCH3 and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position. In some embodiments, E1is -NH- and E2is -CO- and R3and R4are both H and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0353] In some embodiments, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O-. In some embodiments, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2- O-)p, wherein p is 1 , 2, 3 or 4.
[0354] In some embodiments, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4. In some embodiments, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-. In some embodiments, R1is H or methyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0355] In some embodiments, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-.
[0356] In some embodiments, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0357] In some embodiments, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O- CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is - (CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0358] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0359] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments, q is 1 or 2 and r is 1, 2 or 3, preferably 1. In some embodiments of the compound of formula IIId, q is 2 and r is 1, 2 or 3, preferably 1. In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2. In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1- 4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1-3Man-, GlcNAcb1- 6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1- 3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc-, and GalNAcb1-3Gal-. In some preferred embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, GalNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1- 3GlcNAc-, Galα1-4GlcNAc-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1- 4Galβ1-4GlcNAc-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, GlcNAcβ1-3GalNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, Galβ1-4GlcNAcβ1-6GalNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments the compound of formula I is a compound of formula Ia, preferably Ib and the compound of formula II is a compound of formula IIa, preferably IIb and the compound of formula III is a compound of formula IIIa, preferably IIIb: wherein R1is H or linear or branched C1-6alkyl; X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is selected from H, C6-10aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl Y1is a glycosyl moiety. Typically, L1and L3do not form a –O-O-, -S-O- or –N-O- group together. Thus, the method may comprise the steps of a. Reacting a compound of formula Ia, preferably Ib with Y1-OH to generate a compound of formula IIa, preferably IIb: b. Reacting the compound according to formula Ila, preferably lib, with CO2 to generate the compound of formula Illa, preferably lllb: wherein
[0360] R1is H or linear or branched C1-6 alkyl;
[0361] X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is selected from H, C6-10aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl Y1is a glycosyl moiety. In some embodiments, step b. may be performed in the presence of a catalyst, such as a transition metal catalyst, and / or in the presence of a Lewis base, such as an organophosphine, e.g. a tertiary phosphine. In some embodiments, step b. may be performed in the presence of a tertiary phosphine, e.g. a tertiary organophosphine . In some embodiments, step b. may be performed in the presence of a tertiary phosphine P(R10)3: wherein preferably each R10is independently selected from alkyl or aryl. In some embodiments, each R10may be independently selected from C1-12alkyl or C6-14aryl, in particular C1-8 alkyl or C6-C10 aryl. In some embodiments, step b. is performed at about 15 °C to about 35 °C, in particular at about 15 °C to about 30 °C, more particular at about 15 °C to about 25 °C. In some embodiments, step b is performed under a CO2atmosphere at a pressure of 1 bar. or more, in particular at a CO2 pressure of about 1 bar. to about 50 bar, more particular of about 2 bar to about 20 bar, even more particular of about 4 bar to about 10 bar. In some embodiments, step b. is performed in a polar solvent, such as DMF, DMSO, water or mixtures thereof, in particular DMF. In some embodiments, step a. is performed at a pH < 7, in particular < 6. In some embodiments step a. is performed at of about pH 3 to about pH 6, in particular of about pH 4 to about pH 6, more particular of about pH 4.5 to about pH 5.5. In some embodiments, step a. may comprise the addition of an acid, in particular a Bronsted acid. In some embodiments, step a. may comprise the addition of HCl, HNO3or H2SO4, in particular HCl. In some embodiments, step a. may comprise the addition of an acetate salt, such as NH4OAc, NaOAc, LiOAc or the like. In some embodiments, step a. may comprise the addition of an acid. In some embodiments, R1is H or linear C1-4alkyl. In preferred embodiments, R1is H or methyl. In some embodiments, L1is –O-CH2-CO-NH- or –NH-CO-. In some embodiments, L1is – O-CH2-CO-NH-. In some embodiments, L1is –NH-CO-. In some embodiments, L2is –(L3-)n, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2- O-CH2-, and -CH2-CH2-O-. In preferred embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0362] In some embodiments, E1is -NH- and E2is -CO-.
[0363] In some embodiments, R3and R4are independently H or -COCH3. In preferred embodiments, R3and R4are both H.
[0364] In some embodiments, the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0365] In the specification that “the -N3 group and the OH group adjacent to -N3 are both in an equatorial position”, the OH group referred to is the OH group that is directly bonded to the carbon atom which is directly bonded to the anomeric carbon atom. In other words, the OH group referred to is the OH group that is directly bonded to the carbon atom which is directly bonded to the carbon atom which is directly bonded to -N3.
[0366] In some embodiments, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2- O-CH2-, and -CH2-CH2-O- and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, L2is — (L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, - O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O- and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0367] In some embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position. In some embodiments, E1is -NH- and E2is -CO- and R3and R4are independently H or - COCH3. In some embodiments, E1is -NH- and E2is -CO- and R3and R4are both H.
[0368] In some embodiments, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH-. In some embodiments, R1is H or methyl and L1is -O-CH2-CO-NH-.
[0369] In some embodiments, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2- O-CH2-, and -CH2-CH2-O- and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, - O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O- and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0370] In some embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4 and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0371] In some embodiments, the -N3 group and the OH group adjacent to -N3 are both in an equatorial position and R3is H and R4is H. In some embodiments, the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position and R3is H and R4is H.
[0372] In some embodiments, L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0373] In some embodiments, E1is -NH- and E2is -CO- and R3and R4are independently H or - COCH3 and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, E1is -NH- and E2is -CO- and R3and R4are both H and the -N3 group and the OH group adjacent to -N3 are both in an equatorial position. In some embodiments, E1is -NH- and E2is -CO- and R3and R4are independently H or - COCH3 and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position. In some embodiments, E1is -NH- and E2is -CO- and R3and R4are both H and the -N3 group and all other substituents on the hexose to which the -N3 group is directly bonded are in an equatorial position.
[0374] In some embodiments, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, and -CH2-CH2-O-. In some embodiments, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2- O-)p, wherein p is 1 , 2, 3 or 4.
[0375] In some embodiments, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments, R1is H or methyl and L1is -O-CH2-CO-NH- and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0376] In some embodiments, R1is H or linear C1-4 alkyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-. In some embodiments, R1is H or methyl and L1is -O-CH2-CO-NH- and E1is -NH- and E2is -CO-.
[0377] In some embodiments, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-. In some embodiments, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L1is -O-CH2-CO-NH-.
[0378] In some embodiments, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo- glycoside comprising between 2 and 10 glycosides and L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments, R1is H or linear C1-4 alkyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and L2is -(CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0379] In some embodiments, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is -(L3-)n, wherein n is 1 , 2, 3, 4, 5, 6, 7 or 8, wherein L3is, for each occurrence independently, selected from covalent bond, -CH2-, -O- CH2-CH2-, -CH2-O-CH2- and -CH2-CH2-O-. In some embodiments, R1is H or methyl and Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides L2is - (CH2-CH2-O-)P, wherein p is 1 , 2, 3 or 4.
[0380] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0381] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1.
[0382] In some embodiments, q is 1 or 2 and r is 1 , 2 or 3, preferably 1 . In some embodiments of the compound of formula Hid, q is 2 and r is 1 , 2 or 3, preferably 1.
[0383] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2.
[0384] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1 , 2 or 3. In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1 , 2 or 3. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1- 4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1-3Man-, GlcNAcb1- 6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1- 3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-. In some preferred embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, GalNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1- 3GlcNAc-, Galα1-4GlcNAc-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1- 4Galβ1-4GlcNAc-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, GlcNAcβ1-3GalNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, Galβ1-4GlcNAcβ1-6GalNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments the compound of formula I is a compound of formula Ic and the compound of formula II is a compound of formula IIc and the compound of formula III is a compound of formula 11 Ic: wherein wherein
[0385] R1is H or C1-4 alkyl; q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6
[0386] Y1is a glycosyl moiety.
[0387] Thus, the method may comprise the steps of a. Reacting a compound of formula Ic with Y1-OH to generate a compound of formula lie: b. Reacting the compound according to formula He with CO2 to generate the compound of formula I He: wherein R1is H or C1-4 alkyl; q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6
[0388] Y1is a glycosyl moiety.
[0389] In some embodiments of the compound of formula Ic, R1is H or methyl. In some embodiments of the compound of formula Ic, q is 1 or 2, preferably 2.
[0390] In some embodiments of the compound of formula Ic, r is 1 , 2 or 3, preferably 1 .
[0391] In some embodiments of the compound of formula Ic, q is 1 or 2 and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula Ic, q is 2 and r is 1 , 2 or 3, preferably
[0392] 1. In some embodiments, step b. may be performed in the presence of a catalyst, such as a transition metal catalyst, and / or in the presence of a Lewis base, such as an organophosphine, e.g. a tertiary phosphine.
[0393] In some embodiments, step b. may be performed in the presence of a tertiary phosphine, e.g. a tertiary organophosphine . In some embodiments, step b. may be performed in the presence of a tertiary phosphine P(R10)3: wherein preferably each R10is independently selected from alkyl or aryl. In some embodiments, each R10may be independently selected from C1-12 alkyl or C6-14 aryl, in particular C1-8alkyl or C6-C10aryl. In some embodiments, step b. is performed at about 15 °C to about 35 °C, in particular at about 15 °C to about 30 °C, more particular at about 15 °C to about 25 °C. In some embodiments, step b is performed under a CO2 atmosphere at a pressure of 1 bar. or more, in particular at a CO2 pressure of about 1 bar. to about 50 bar, more particular of about 2 bar to about 20 bar, even more particular of about 4 bar to about 10 bar. In some embodiments, step b. is performed in a polar solvent, such as DMF, DMSO, water or mixtures thereof, in particular DMF. In some embodiments, step a. is performed at a pH < 7, in particular < 6. In some embodiments step a. is performed at of about pH 3 to about pH 6, in particular of about pH 4 to about pH 6, more particular of about pH 4.5 to about pH 5.5. In some embodiments, step a. may comprise the addition of an acid, in particular a Bronsted acid. In some embodiments, step a. may comprise the addition of HCl, HNO3 or H2SO4, in particular HCl. In some embodiments, step a. may comprise the addition of an acetate salt, such as NH4OAc, NaOAc, LiOAc or the like. In some embodiments, step a. may comprise the addition of an acid. In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides. In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and r is 1, 2 or 3, preferably 1. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1, 2 or 3, preferably 1. In some embodiments, q is 1 or 2 and r is 1, 2 or 3, preferably 1. In some embodiments of the compound of formula IIId, q is 2 and r is 1, 2 or 3, preferably 1. In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2. In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1- 4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1-3Man-, GlcNAcb1- 6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1- 3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-. In some preferred embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-,GalNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1- 3GlcNAc-, Galα1-4GlcNAc-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1- 4Galβ1-4GlcNAc-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, GlcNAcβ1-3GalNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, Galβ1-4GlcNAcβ1-6GalNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments the compound of formula I is a compound of formula Id and the compound of formula II is a compound of formula IId and the compound of formula III is a compound of formula IIId: wherein q is 0, 1 , 2, 3 or 4; r is 1 , 2, 3, 4, 5 or 6. Y1is a glycosyl moiety.
[0394] Thus, the method may comprise the steps of a. Reacting a compound of formula Id with Y1-OH to generate a compound of formula lid: b. Reacting the compound according to formula lid with CO2 to generate the compound of formula II Id: wherein
[0395] R1is H or C1-4 alkyl; q is 0, 1, 2, 3 or 4; r is 1, 2, 3, 4, 5 or 6 Y1is a glycosyl moiety. In some embodiments, q is 1 or 2, preferably 2. In some embodiments, r is 1, 2 or 3, preferably 1. In some embodiments, step b. may be performed in the presence of a catalyst, such as a transition metal catalyst, and / or in the presence of a Lewis base, such as an organophosphine, e.g. a tertiary phosphine. In some embodiments, step b. may be performed in the presence of a tertiary phosphine, e.g. a tertiary organophosphine . In some embodiments, step b. may be performed in the presence of a tertiary phosphine P(R10)3: wherein preferably each R10is independently selected from alkyl or aryl. In some embodiments, each R10may be independently selected from C1-12alkyl or C6-14aryl, in particular C1-8 alkyl or C6-C10 aryl. In some embodiments, step b. is performed at about 15 °C to about 35 °C, in particular at about 15 °C to about 30 °C, more particular at about 15 °C to about 25 °C. In some embodiments, step b is performed under a CO2 atmosphere at a pressure of 1 bar. or more, in particular at a CO2 pressure of about 1 bar. to about 50 bar, more particular of about 2 bar to about 20 bar, even more particular of about 4 bar to about 10 bar.
[0396] In some embodiments, step b. is performed in a polar solvent, such as DMF, DMSO, water or mixtures thereof, in particular DMF.
[0397] In some embodiments, step a. is performed at a pH < 7, in particular < 6. In some embodiments step a. is performed at of about pH 3 to about pH 6, in particular of about pH 4 to about pH 6, more particular of about pH 4.5 to about pH 5.5.
[0398] In some embodiments, step a. may comprise the addition of an acid, in particular a Bronsted acid. In some embodiments, step a. may comprise the addition of HCI, HNO3 or H2SO4, in particular HCI. In some embodiments, step a. may comprise the addition of an acetate salt, such as NH4OAC, NaOAc, LiOAc or the like. In some embodiments, step a. may comprise the addition of an acid.
[0399] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides. In preferred embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides.
[0400] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and r is 1 , 2 or 3, preferably 1. In some embodiments of the compound of formula Hid, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and r is 1 , 2 or 3, preferably 1.
[0401] In some embodiments, q is 1 or 2 and r is 1 , 2 or 3, preferably 1 . In some embodiments of the compound of formula Hid, q is 2 and r is 1 , 2 or 3, preferably 1.
[0402] In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2, preferably 2. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2, preferably 2. In some embodiments, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments of the compound of formula IIId, Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 6 glycosides and q is 1 or 2 and r is 1, 2 or 3. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. In some embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1- 6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1- 6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6- Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1- 3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1- 4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1-4Galβ1- 4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1- 5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1- 6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1- 3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1- 3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1- 3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1- 3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su- Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1- 6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1- 4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1-3Man-, GlcNAcb1- 6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1- 3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-. In some preferred embodiments, Y1is selected from Rha-, ManNAc-, GlcNAc-, GalNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1- 3GlcNAc-, Galα1-4GlcNAc-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1- 4Galβ1-4GlcNAc-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, GlcNAcβ1-3GalNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, Galβ1-4GlcNAcβ1-6GalNAc- and GlcNAcβ1-2Galβ1-3-GalNAc. Examples Example 1 Step 1: Synthesis of compound 2: NaOAc (276 mg) and acetic acid (81 mg) is dissolved in water (48 mL), and the pH of the solution is adjusted to ~4,5, by addition of HCl-solution. The N-methyl hydroxylamine derivative 1 (1000 mg) is dissolved in 24 mL of the above solution, and melibiose monohydrate (850 mg) is added in one portion. The slightly turbid reaction mixture is stirred at 36-38 °C at pH~4,5 for 3 days. The solution is concentrated in vacuo to a colorless glassy solid (2,07 g). The crude product is purified on a column of silica (350 g), (eluent: EtOAc : MeOH : water = 5 : 4 : 1) to yield 680 mg product. NMR data of product:1H NMR (300 MHz, D2O): 4.96 (d, 1H), 4.27 (s, 2H), 4.13 (d, 1H), 4.00-3.89 (m, 4H), 3.86- 3.72 (m, 3H), 3.70-3.58 (m, 10H), 3.57-3.35 (m, 10H), 3.30 (m, 4H), 2.97 (s, 3H)13C NMR (300 MHz, D2O): 171.86, 170.05, 98.01, 93.79, 90.11, 77.26, 76.80, 76.26, 75.28, 72.38, 71.46, 71.07, 70.92, 69.76, 69.56, 69.50, 69.45, 69.40, 69.22, 68.68, 68.42, 61.09, 48.91, 38.98, 38.90, 38.61. Step 2: Synthesis of compound 3
[0403] The starting material 2 (680 mg) was dissolved in dry DMF (12 ml). Polymer bound triphenylphosphine (2.0 g) (washed with DMF, and dried in vac. drying oven over P2O5 at r.t. for 2 days) is added. The reaction mixture is stirred at 20 °C in CO2 atmosphere (5 - 5,5 bar) for 12 hours. The solid is filtered out, washed with dry DMF (9 mL) and the filtrate is concentrated in vacuo (final vacuum 2 mbar / 40 °C. The residue yellow glassy solid (850 mg) is dissolved in mixture of water (25 mL) and MeOH (12 mL), activated carbon (50 mg) is added, stirred for 5 min. at r.t., and then filtered. The filter is washed with water (5 mL), and the aq. solution is cooled with liquid nitrogen, and lyophilized to yield 615 mg product as white solid. NMR data of product:1H NMR (300 MHz, D2O): 5.02 (d, 1H), 4.28 (s, 2H), 4.13-4.05 (m, 3H), 4.00-3.92 (m, 6H), 3.84-3.73 (m, 6H), 3.72-3.68 (m, 4H), 3.67-3.52 (m, 12H), 3.50-3.39 (m, 10H), 2.97 (s, 3H)13C NMR (300 MHz, D2O):171.86, 169.71, 98.01, 93.79, 90.12, 85.04, 81.10, 79.13, 77.26, 76.26, 75.29, 73.23, 72.52, 71.47, 71.07, 70.93, 69.76, 69.56, 69.47, 69.41, 69.22, 68.68, 68.42, 65.56, 61.10, 38.99, 38.91, 38.62 Ligation of Bovine serum albumin (BSA) with compound 3 In 0.5 ml solution of BSA (5 mg) and compound 3 (9.5 mg, 0.0125 mmol) in PBS buffer the pH was set to 7.4 and incubated in a thermal shaker at 37°C for 3 hours. The solution was deionized and the excess of ligating probe was removed by centrifugal filter (cut-off 10 kDa). The solution was analyzed by MALDI: BSA standard: 66435 m / z Ligated BSA: 69463 m / z (4 average ligation / BSA). Ligation of Ovalbumin (OVA) with compound 3 In 0.5 ml solution of OVA (InvivoGen EndoFit Ovalbumin) (10 mg) and compound 3 (34 mg, 0.045 mmol) in PBS buffer the pH was set to 8 and incubated in a thermal shaker at 37°C for 20 hours. The solution was deionized and the excess of ligating probe was removed by centrifugal filter (cut-off 10 kDa). The solution was analyzed by MALDI: OVA standard: 44316 m / z Ligated OVA: 46310 m / z (2.6 average ligation / BSA).
[0404] Ligation of murine melanoma cells with compound 3
[0405] 5x105B16.F10 murine melanoma cells were freshly brought to single cell suspension from their culture in T25 flasks (Corning, TC-treated), washed with 1 ml of 1( Dulbecco’s PBS (Gibco), centrifuged at 450 g and 4 °C for 5 min, and resuspended in 500 pl of 10 mM compound 3 ligating probe prepared in DPBS. Cells were incubated in a thermoblock at 37 °C for 3 h while mildly agitating. Afterwards the cells were washed and centrifuged three times with 1 ml 100 mM glycine prepared in DPBS. The sample was processed for flow cytometry detection of bound melibiose by using either murine or human anti-Mel antibodies. For the detection by murine antibodies, cells were incubated for 1 hour at 4 °C with 1 :300 serum dilutions of mice which were subcutaneously immunized with melibiose- ligated Keyhole limpet hemocyanin For the detection by human antibodies, cells were incubated for 1 hour at 4 °C with 40 pg / ml dilutions of human total IgG fractions which were purified from pooled human healthy donor serums (in. vent Diagnostica; 2.3 mg / ml total protein concentration). Cells were washed and 25 pelleted in ice-cold FACS buffer (1X PBS, 2% BSA). Bound murine and human anti-Mel antibodies were detected by 1 :200 dilutions of FITC-conjugated polyclonal rabbit anti-mouse or anti-human IgG F(ab')2 antibodies (Jackson Immunoresearch; 1.4 mg / ml and 1.5 mg / ml, respectively).
[0406] Synthesis of compound 6
[0407]
[0408] NH4OAC (1.54 g) is dissolved in water (15 mL), and the pH of the solution is adjusted to ~5, by addition of HCI-solution. Compound 5 (720 mg) is dissolved in the above solution, and lactose (730 mg) is added in one portion. The slightly turbid reaction mixture is stirred at 36- 38 °C. The reaction is monitored by TLC (eluent: EtOAc : MeOH : water = 5 : 4 : 1). Full conversion is reached after 2 days. The solution is concentrated in vacuo and the crude product (2.2 g) is purified on a column of silica, (eluent: EtOAc : MeOH : water = 5 : 4 : 1) to yield 760 mg product (compound 6) as colorless syrup.
[0409] Synthesis of compound 7 The starting material 6 (630 mg) was dissolved in dry DMF (4 ml). Polymer bound triphenylphosphine (2.0 g) (washed with DMF, and dried in vac. drying oven over P2O5 at r.t. for 2 days) is added. The reaction mixture is stirred at 20 °C in CO2 atmosphere (5 - 5,5 bar) for 19 hours. The solid is filtered out, washed with dry DMF (2 x 3 mL) and the filtrate is concentrated in vacuo (final vacuum 2 mbar 1 40 °C. The residue yellow syrup (688 mg) is dissolved in mixture of water (30 ml), activated carbon (50 mg) is added, stirred for 5 min. at r.t., and then filtered. The filter is washed with water (5 mL), and the aq. solution is cooled with liquid nitrogen, and lyophilized to yield 362 mg product (compound 7) as white solid.
[0410] LC-MS Data of product: Column: Tosoh Bioscience, TSKgel Amide, 80 A, 3 mm, 4.6x150 mm
[0411] Gradient: 70-62% B in A in 12 min, 1 mL / min
[0412] Eluent: A: 10 mM AF in waterB: Acetonitrile
[0413] Retention time: 5.6-8.0 min (Broad peak, mixture of pyranose and furanose form of glucose)
[0414] MS - positive mode: 769 (746+Na+) MS - negative mode : 745 (746-H+)
[0415] Example 3
[0416] Synthesis of compound 9
[0417]
[0418] NH4OAC (1.54 g) is dissolved in water (15 mL), and the pH of the solution is adjusted to ~5, by addition of HCI-solution. Compound 5 (770 mg) is dissolved in the above solution, and rhamnose (300 mg) is added in one portion. The slightly turbid reaction mixture is stirred at 36-38 °C for 2 days. The solution is concentrated in vacuo and the crude product (1.83 g) is purified on a column of silica, (eluent: EtOAc : MeOH : water = 5 : 4 : 1) to yield 390 mg product (compound 9).
[0419] Synthesis of compound 10 The starting material 9 (360 mg) was dissolved in dry DMF (2 ml). Polymer bound triphenylphosphine (1.0 g) (washed with DMF, and dried in vac. drying oven over P2O5 at r.t. for 2 days) is added. The reaction mixture is stirred at 20 °C in CO2 atmosphere (5 - 5,5 bar) for 12 hours. The solid is filtered out, washed with dry DMF (9 mL) and the filtrate is concentrated in vacuo (final vacuum 2 mbar 1 40 °C. The residue yellow glassy solid (850 mg) is dissolved in mixture of water (20 mL), activated carbon (30 mg) is added, stirred for 5 min. at r.t., and then filtered. The filter is washed with water (3 mL), and the aq. solution is cooled with liquid nitrogen, and lyophilized to yield 255 mg product (compound 10) as white solid. LC-MS Data of product:
[0420] Column: Tosoh Bioscience, TSKgel Amide, 80 A, 3 mm, 4.6x150 mm
[0421] Gradient: 70-62% B in A in 12 min, 1 mL / min
[0422] Eluent: A: 10 mM AF in waterB: Acetonitrile
[0423] Retention time: 3.2 min and 4.1 min (Two peaks, pyranose and furanose form of glucose) MS (3.2 min.) - positive mode: 591 (568+Na+)
[0424] MS (3.2 min.) - negative mode : 567 (568-H+)
[0425] MS (4.1 min.) - positive mode : 591 (568+Na+)
[0426] MS (4.1 min.) - negative mode : 567 (568-H+)
[0427] Synthesis of compound 11 : NaOAc (431 mg) and acetic acid (127 mg) is dissolved in water (75 mL), and the pH of the solution is adjusted to ~4,5, by addition of HCl-solution. The N-methyl hydroxylamine derivative 1 (1000 mg) is dissolved in 25 mL of the above solution, and N-acetyl-glucosamine (1500 mg) is added in one portion. The slightly turbid reaction mixture is stirred at 36-38 °C at pH~4,5 for 7 days. The solution is lyophilized (2,59 g). The crude product is dissolved in EtOAc : MeOH : water = 5 : 4 : 1 mixture (~5 ml) and the precipitated N-acetyl-glucosamine was removed by filtration. The clear solution of the crude product is purified on a column of silica (80 g) two times, (eluent: EtOAc : MeOH : water = 5 : 4 : 1) to yield 385 mg product. NMR data of product:1H NMR (700 MHz, D2O): 4.73 (d, 1H), 4.24 (d, 1H), 4.12 (q, 2H), 3.89 (d, 1H), 3.87 (d, 1H), 3.81 (t, 1H), 3.70 (m, 1H), 3.61(s, 4H), 3.58 (m, 4H), 3.49 (m, 3H), 3.38 (m, 6H), 3.25, (t, 1H), 2.70 (s, 3H), 1.95 (s, 3H)13C NMR (700 MHz, D2O): 174.30, 171.73, 170.02, 92.16, 90.09, 76.78, 76.67, 75.23, 72.33, 72.15, 71.16, 71.02, 69.47, 69.43, 68.71, 68.65, 67.90, 61.09, 49.06, 38.86, 38.52, 38.06, 22.24 Synthesis of compound 12 The starting material 11 (360 mg) was dissolved in dry DMF (6 ml). Polymer bound triphenylphosphine (950 mg) (washed with DMF, and dried in vacuum drying oven over P2O5 at r.t. for 3 days) is added. The reaction mixture is stirred at 20 °C in CO2 atmosphere (5,5 bar) for 24 hours. The solid is filtered out, washed with dry DMF (2 x 3 mL) and the filtrate is concentrated in vacuo (final vacuum 2 mbar / 40 °C. The residue yellow syrup (557 mg) is dissolved in mixture of water (4 mL) and MeOH (1.5 mL), activated carbon (50 mg) is added, stirred for 15 min. at r.t., and then filtered. The filter is washed with water (4 mL), and the clear colorless solution is cooled with liquid nitrogen, and lyophilized to yield 353 mg product as white solid.
[0428] LC-MS data of product:
[0429] Column: Tosoh Bioscience, TSKgel Amide, 80 A, 3 mm, 4.6x150 mm
[0430] Gradient: 70-62% B in A in 12 min, 1 mL / min
[0431] Eluent: A: 10 mM AF in waterB: Acetonitrile
[0432] Retention time: 3.5-7.0 min (Broad peak)
[0433] MS - positive mode: 662 (639+Na+)
[0434] MS - negative mode : 638 (639-H+)
[0435] Ligation of Ovalbumin (OVA) with compound 12
[0436] In 1.5 ml solution of OVA (30 mg) and compound 12 (96 mg, 0.150 mmol) in PBS buffer the pH was set to 8.5 and incubated in a thermal shaker at 37°C for 20 hours. The solution was deionized and the excess of ligating probe was removed by centrifugal filter (cut-off 10 kDa). The solution was lyophilized to yield 28.9 mg product. The solution was analyzed by MALDI: OVA standard: 39884 m / z and 44357 m / z Ligated OVA: 40686 m / z and 44985 m / z (1.1 average ligation / OVA). Synthesis of compound 13 NaOAc (431 mg) and acetic acid (127 mg) is dissolved in water (75 mL), and the pH of the solution is adjusted to ~4,5, by addition of HCl-solution. The N-methyl hydroxylamine derivative 1 (1000 mg) is dissolved in 25 mL of the above solution, and N-acetyl-glucosamine (1500 mg) is added in one portion. The slightly turbid reaction mixture is stirred at 36-38 °C at pH~4,5 for 7 days. The solution is lyophilized (2,58 g). The crude product is purified on a column of silica (80 g), (eluent: EtOAc : MeOH : water = 5 : 4 : 1) to yield 355 mg product. NMR data of product:1H NMR (300 MHz, D2O): 4.73 (d, 1H), 4.18 (d, 1H), 4.12 (q, 2H), 4.00 (t, 1H), 3.89 (m, 2H), 3.77 (dd, 1H), 3.69 (dd, 1H), 3.65 (dd, 1H), 3.62 (s, 4H), 3.58 (m, 5H), 3.50 (m, 2H), 3.39 (m, 4H), 3.25 (t, 1H), 2.71 (s, 3H), 1.95 (s, 3H)13C NMR (300 MHz, D2O): 175.10, 172.33, 171.02, 92.87, 90.25, 77.09, 76.96, 75.51, 72.69, 72.25, 71.43, 71.09, 69.74, 69.64, 69.01, 68.87, 68.13, 61.60, 49.55, 39.02, 38.83, 38.27, 22.35 Synthesis of compound 14
[0437] The starting material 13 (320 mg) was dissolved in dry DMF (6 mL). Polymer bound triphenylphosphine (850 mg) (washed with DMF, and dried in vacuum drying oven over P2O5 at r.t. for 3 days) is added. The reaction mixture is stirred at 20 °C in CO2 atmosphere (5,5 bar) for 24 hours. The solid is filtered out, washed with dry DMF (2 x 5 mL) and the filtrate is concentrated in vacuo (final vacuum 2 mbar / 40 °C. The residue yellow syrup (471 mg) is dissolved in mixture of water (4 mL) and MeOH (1 mL), activated carbon (50 mg) is added, stirred for 5 min. at r.t., and then filtered. The filter is washed with water (4 mL), and the clean, colorless solution is cooled with liquid nitrogen, and lyophilized to yield 313 mg product as white solid.
[0438] LC-MS data of product:
[0439] Column: Tosoh Bioscience, TSKgel Amide, 80 A, 3 mm, 4.6x150 mm
[0440] Gradient: 70-62% B in A in 12 min, 1 mL / min
[0441] Eluent: A: 10 mM AF in waterB: Acetonitrile Retention time: 3.5-6.3 min (Broad peak)
[0442] MS - positive mode: 662 (639+Na+)
[0443] MS - negative mode : 638 (639-H+)
[0444] Ligation of Ovalbumin (OVA) with compound 14 In 1.5 ml solution of OVA (30 mg) and compound 14 (96 mg, 0.150 mmol) in PBS buffer the pH was set to 8.5 and incubated in a thermal shaker at 37°C for 20 hours. The solution was deionized and the excess of ligating probe was removed by centrifugal filter (cut-off 10 kDa). The solution was lyophilized to yield 26.1 mg product. The solution was analyzed by MALDI : OVA standard: 39884 m / z and 44357 m / z Ligated OVA: 41623 m / z and 45920 m / z (2.6 average ligation / OVA).
Claims
Claims 1. A compound of formula III:wherein R1is H or linear or branched C1-6 alkyl;X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl; Y1is a glycosyl moiety.
2. The compound according to claim 1, wherein the compound of formula III is a compound of formula IIIa:wherein R1is H or linear or branched C1-6 alkyl;X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety.
3. The compound according to any one of claims 1-2, wherein R1is H or linear C1-4 alkyl, preferably H or methyl.
4. The compound according to any one of claims 1-3, wherein L1is.
5. The compound according to any one of claims 1-4, wherein Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides, in particular between 2 and 8 glycosides, in particular between 2 and 6 glycosides.
6. The compound according to any one of claims 1-5, wherein Y1is selected from is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1- 4GlcNAc-, 6-Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1- 3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1- 4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2- 3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su- GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)- 3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3- GalNAc, GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1- 4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1- 4Glc-, GlcNAcb1-3Man-, GlcNAcb1-6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal,GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1-3Gala1-4Galb1-4Glc-, GalNAcb1- 3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-.
7. Method of glycosylating a cell, comprising the step of reacting a compound according to any one of claims 1-6 with an –NH2 group at the cell surface to generate a glycosylated cell.
8. Method of glycosylating a protein of interest, comprising the step of reacting a compound according to any one of claims 1-6 with an –NH2 group of a protein of interest to generate a glycosylated protein.
9. A cell comprising at least one functionalized amino moiety at the cell surface, the functionalized amino moiety having the general formula IV:wherein R1is H or linear or branched C1-6 alkyl;X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear orbranched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl; Y1is a glycosyl moiety.
10. The cell according to claim 9, wherein the functionalized amino moiety has the general formula IVa:wherein R1is H or linear or branched C1-6alkyl; L1X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety.
11. The cell according to any one of claims 9-10, wherein R1is H or linear C1-4alkyl, preferably H or methyl.
12. The cell according to any one of claims 9-11, wherein L1isor.
13. The cell according to any one of claims 9-12, wherein Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides, in particular between 2 and 8 glycosides, in particular between 2 and 6 glycosides.
14. The cell according to any one of claims 9-13, wherein Y1is selected from is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1- 2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1-3GlcNAcα1-6Galβ1- 4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1-4GlcNAc-, 6-Bn-Galα1-4(6- Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1-4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2-3Galβ1-4Glc-, GlcNAcβ1- 4Galβ1-4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1- 4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2- 4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1- 3Galα1-4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su-GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)-3GlcNAc-, Galα1- 3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1- 4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1- 3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3-GalNAc, GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1-4Glc-, GlcNAcb1-3Man-, GlcNAcb1-6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1- 4Glc-, GalNAcb1-3Gala1-4Galb1-4Glc-, GalNAcb1-3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-.
15. A protein comprising at least one functionalized amino moiety, the functionalized amino moiety having the general formula V:wherein R1is H or linear or branched C1-6 alkyl;X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl; Y1is a glycosyl moiety.
16. The protein according to claim 15, wherein the functionalized amino moiety has the general formula Va:wherein R1is H or linear or branched C1-6 alkyl;X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl; Y1is a glycosyl moiety.
17. The protein according to any one of claims 15-16, wherein R1is H or linear C1-4alkyl, preferably H or methyl.
18. The protein according to any one of claims 15-17, wherein L1isor.
19. The protein according to any one of claims 15-18, wherein Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides, in particular between 2 and 8 glycosides, in particular between 2 and 6 glycosides.
20. The protein according to any one of claims 15-19, wherein Y1is selected from is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1- 4GlcNAc-, 6-Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1- 3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1- 4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2- 3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su- GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)- 3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1- 6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-,Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3- GalNAc, GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1- 4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1- 4Glc-, GlcNAcb1-3Man-, GlcNAcb1-6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1-3Gala1-4Galb1-4Glc-, GalNAcb1- 3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-.
21. A compound of formula I:wherein R1is H or linear or branched C1-6 alkyl;X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or a covalent bond; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl.
22. The compound according to claim 21, wherein the compound of formula I is a compound of formula Ia:wherein R1is H or linear or branched C1-6alkyl;X1is selected from -O-, -S- or -NH-; each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10 aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10aryl and linear or branched alkyl.
23. A compound of formula II:wherein R1is H or linear or branched C1-6alkyl;X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6alkyl, wherein R6is selected from H, C6-10aryl, linear or branched C1-6alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety.
24. The compound according to claim 23, wherein the compound of formula II is a compound of formula IIa:wherein R1is H or linear or branched C1-6alkyl;X1is selected from -O-, -S- or -NH-;each L3is independently a covalent bond, -CH2-, -O-CH2-CH2-, -CH2-O-CH2-, or - CH2-CH2-O-; n is 1, 2, 3, 4, 5, 6, 7 or 8; m is 1, 2, 3 or 4; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is independently selected from H, C6-10aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety.
5. The compound according to any one of claims 23-24, wherein Y1is a mono-glycoside or an oligo-glycoside comprising between 2 and 10 glycosides, in particular between 2 and 8 glycosides, in particular between 2 and 6 glycosides.
6. The compound according to any one of claims 23-25, wherein Y1is selected from is selected from Rha-, ManNAc-, GlcNAc-, Galβ1-4Glc-, Galβ1-6Galβ1-4Glc-, GlcNAcβ1-2Galβ1-3GalNAc-, GlcNAcβ1-6(GlcNAcβ1-4)GalNAc-, Galα1-6Glc-, Galα1-3GlcNAc-, GalNAcα1-3GalNAc-, GlсNAcβ1-4(6-O-Su)GlcNAc-, Galβ1- 3GlcNAcα1-6Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-3GlcNAc-, Galα1- 4GlcNAc-, 6-Bn-Galα1-4(6-Bn)GlcNAc-, GlcNAcβ1-4-MurNAc-, GlcNAcβ1-4Mur-, GalNAcα1-3GalNAcβ1-3Gal-, Galα1-4GlcNAcβ1-3Galβ1-4GlcNAc-, Galβ1- 3GlcN(Fm)β1-3Galβ1-4GlcNAc-, GlcNAcβ1-4GlcNAc-, Galα1-2Gal-, Galα1-3Galβ1- 4Glc-, GlcNAcα1-3GalNAc-, Neu5Acα2-8Neu5Ac-, Fucα1-2Galβ1-4Glc-, Neu5Acα2- 3Galβ1-4Glc-, GlcNAcβ1-4Galβ1-4GlcNAc-, Neu5Acα2-8Neu5Acα2-4Neu5Ac-, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-, Galβ1-4GlcNAcβ1-3Galβ1-4Glc-, Galα1-3Galβ1- 4GlcNAcβ1-3Galβ1-4Glc-, Arafβ1-2Arafα1-5(Arafβ1-2Arafα1-3)Arafα1-5Araf-, Neu5Acα2-8Neu5Acα2-4Neu5Acα2-6GlcNAcβ1-6GlcNAc-, Fucα1-4GlcNAc-, GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, GlcNAcα1-3Galβ1-4GlcNAc-, 3-O-Su- GlcNAc-, 6-O-Su-Gal-, GalNAcα1-3Gal-, GlcNAcβ1-3GalNAc-, (6-O-Bn-Galβ1)- 3GlcNAc-, Galα1-3GalNAc(fur)-, 4,6-O-Su2-Galβ1-4GlcNAc-, GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-, Galβ1-4Galβ1-4GlcNAc-, GalNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcNAcα1-3Galβ1-4GlcNAc-, Galβ1-3GlcN(Fm)β1-3Galβ1-3GlcNAc-, Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-, Galβ1-3GalNAc(fur)-, Fucα1-3GlcNAc-, Fucβ1-3GlcNAc-, Galβ1-3GlcNAc-, GlcNAcβ1-6GalNAc-, 3-O-Su-Galβ1-3GlcNAc-, 6-O-Su-Galβ1-3GlcNAc-, GlcAβ1-3GlcNAc-, 3,4-O-Su2-GalNAcβ1-4GlcNAc-, Galβ1-4GlcNAcβ1-6GalNAc-, GlcNAcβ1-4Galβ1-4GlcNAc-, GlcNAcβ1-2Galβ1-3- GalNAc, GlcNAcb1-4GlcNAc-, GlcNAcb1-4GlcNAcb1-4GlcNAc-, GlcNAcb1- 4GlcNAcb1-4GlcNAcb1-4GlcNAc-, A2G0, A2G1, A2G0F, A2G1F, GlcNAcb1-3Galb1- 4Glc-, GlcNAcb1-3Man-, GlcNAcb1-6Galb1-4Glc-, GalNAc-, GalNAcb1-4Gal, GalNAcb1-4(Siaa2-3)Galb1-4Glc-, GalNAcb1-3Gala1-4Galb1-4Glc-, GalNAcb1- 3Gala1-3Galb1-4Glc- and GalNAcb1-3Gal-.
27. The compound according to any one of claims 21-26, wherein R1is H or linear C1-4alkyl, preferably H or methyl.
28. The compound according to any one of claims 21-27, wherein L1is.
29. A method of generating a compound of formula III, the method comprising the steps of: a. Reacting a compound of formula I with Y1-OH to generate a compound of formula II:b. Reacting the compound according to formula II with CO2to generate the compound of formula III:wherein R1is H or linear or branched C1-6 alkyl;X1is selected from -O-, -S- or -NH-; L2is a polyalkylether, alkyl or absent; m is 1, 2, 3 or 4; E1is selected from –O-, -S- or –NH-; E2is selected from –CO- or –CH2-; R3and R4are independently selected from H, R5-CO-, R5-CH2-, R6-CH2-O-CH2-, - SiR7R8R9, wherein R5is selected from H, C6-10 aryl, vinyl, linear or branched C1-6 alkyl, wherein R6is selected from H, C6-10 aryl, linear or branched C1-6 alkyl, wherein R7, R8and R9are independently selected from C6-10 aryl and linear or branched alkyl; Y1is a glycosyl moiety.
30. The method according to claim 29, wherein step b. is performed in the presence of a tertiary phosphine.
31. The method according to claim 29 or 30, wherein step a. is performed at a pH < 7, in particular < 6.