FR2892419A1 - HETEROLIGOMERS OF D-GLUCASAMINE AND N-ACETYL-D-GLUCOSAMINE, PROCESS FOR THE PREPARATION THEREOF AND USE THEREOF - Google Patents

Abstract

The subject of the present invention is novel glycosidic oligomers, monomers useful for their preparation, as well as a process for the preparation of such oligomers and in particular of hetero-oligomers of D-glucosamine and N-acetyl-D-glucosamine, allowing to control the size, the degree of acetylation and the architecture of the oligomers obtained.

Description

The subject of the present invention is new glycosidic oligomers,

  monomers useful for their preparation, as well as a process for the preparation of such oligomers. Biopolymers, such as chitosan, have interesting biological properties. Chitosan is a biodegradable and bioabsorbable natural fiber obtained after deacetylation of chitin. Chitin is a biopolymer of high molecular weight, non-toxic, biodegradable and bioabsorbable, and it is with cellulose, the most common polysaccharide in nature. Chitin is a linear copolymer chain whose structure contains D-glucosamine monomers and N-acetyl-D-glucosamine monomers linked through a p- (1-4) linkage. The extraction of chitin from crustacean shell and / or squid is usually done chemically, then the conversion by deacetylation of chitin in concentrated soda produces chitosan. Chitosan is therefore obtained by removing sufficient acetyl groups to allow the macromolecule to be soluble in most dilute acids. Chitin and chitosan are known to have multiple biological properties, and are likely to be used in many fields, such as water treatment, in pharmacy or cosmetics, or in agriculture, agri-food or biotechnology. Therapeutic applications of chitin and chitosan were explored, which made it possible to highlight their anti-tumor, antibacterial, hypocholesterolemic or anti-hypertensive activity.

  However, their high molecular weight and high viscosity may reduce their absorption in the gut in humans. Therefore, work has been carried out to obtain oligomers of / acetyl-D-glucosamine and D-glucosamine which have lower molecular weight, lower viscosity, which should facilitate their absorption in vivo, as well as their solubility in neutral aqueous solutions.

  The preparation of such oligomers has, in most cases, been carried out by chemical or enzymatic hydrolysis of chitin or chitosan as described by Y-J. Jeon, F. Shahidi, Kim S-K, Food Rat /. Int, 16 (2), 159-176 (2000). Such techniques lead to mixtures of oligomers consisting of units / If-acetyl-D-glucosamine and D-glucosamine, with average degrees of polymerization, but do not allow a control of the size nor of the distribution along of the chain of the two constituent units. Studies have shown that such mixtures of oligomers of / IFacetyl-D-glucosamine and / or D-glucosamine have interesting biological properties (anti-tumor activities, fungistatic activities, antimicrobial activities, eliciting properties ...). For more details, refer to publication Y-J. Jeon, F. Shahidi, Kim S-K, Food Rev. Int, 16 (2), 159-176 (2000). A total chemical synthesis approach was also used to prepare two oligomers of / V-acetyl-D-glucosamine, with degrees of polymerization 4 and 6 (see M.Aly et al., Carbohydr Res., 331 (2001)). ), 129-142). This manufacturing method described in this publication only leads to oligomers consisting of a single elementary unit, called homo-oligomers and is not suitable for the synthesis of heterooligomers. One of the objectives of the present invention is thus to overcome the drawbacks of the prior art and to provide oligomers of / I / -acetyl-D-glucosamine and D-glucosamine, in which the functions OH, -NH 2 or -NHAc are optionally in protected form, in pure form, whatever their degree of polymerization (DP), their degree of acetylation (DA) and the distribution of the units / V-acetyl-D-glucosamine and D-glucosamine along the polymer chain. According to one of its aspects, the subject of the invention is oligomers of formula (I): R5-P-R4 in which P consists of at least two glycosyl units chosen from glucosamine units of formula: linked together by a Binding [3- (1--4), wherein: - R1, R2, R'1 and R'2 each independently represent a hydrogen atom or an alcohol protecting group, R3 and R'3 each represent independently: an amine protecting group, for orienting the linkage (1-4), upon glycosidic coupling, to [3 and leading after deprotection to an -NH2 function, under conditions which do not modify a protected amine group which may lead, under other deprotection conditions, to a group with NHAc, or a group protecting the amines, which makes it possible to orient the linkage (1 to 4), during a glycosidic coupling, to (3 and leading after deprotection to a -NHAc function, under conditions that do not modify a grouping a protected amine capable of leading under other deprotection conditions to a -NH2 group, or else R3 and R'3 each independently represent a hydrogen atom or an acetyl group, it being understood that at least R3 or R'3 is different from the acetyl group, R4 is a hydroxyl group, or a hydroxyl group in protected form preferably in position 13, or a group preferably leaving in position a, said leaving group being capable of R3NH and the units N acetyl-D-glucosamine of the formula: OR'1 R'3NH form an oxy-bridge on a 13- (1-4) bond with a free OHo located in the 4-position of another glycosyl group, and R5 is a hydrogen atom or an alcohol-protecting group . According to preferred aspects, the oligomers according to the invention have one or other of the following characteristics, or any combination of these characteristics, when they do not exclude each other: The oligomer is one of the following formulas wherein: • the glycosyl units are linked together by a 13- (1--4) bond • R1r R2, R'1, R'2 , R3, R'3, R4 and R5 are as defined above for the compounds of formula (I), • n and m represent, each independently, 1, 2, 3, 4, 5, 6 or 7 and p is equal to at 1, 2, 3 or 4, it being understood that p * (n + m) is less than or equal to 8, the compounds (Ia) and (Ib) in which n = m = p = 1 constitute a particular aspect of the invention; - R3 = HetR'3 = Ac; R3 is -C (O) ORd, where Rd is selected from benzyl, para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, R5 [L0 R20 OR'1 R5 [OO R'20 R20 NHR'3 NHR3 ( Ib) para-chlorobenzyl, 2,4-dichlorobenzyl, R3 being preferably a benzyloxycarbonyl group; R'3 is a dichloroacetyl, chloroacetyl, or preferably trichloroacetyl group; R5 is selected from -C (O) Ra groups, with Ra = -CH3, -CH2Cl, -CHCl2, -CCl3, -CF3, -CH2OMe, -CH2OCPh3, -CH2OC6H4-p-Cl, -C (CH3) 3 - Ph or -C6H4 (p-MeO); R4 is selected from the group -OSi (CH3) 2C (CH3) 3, -OSiPh2C (CH3) 3, -OC6H4-p-OMe, -OCH2CH = CH2, -OCH2CH2CH2CH = CH2, -SPh, -SEt, - OC (NH) CCI3; - R1, R'1, R2 and R'2, identical or different, are selected from benzyl, para-methoxybenzyl, para-nitrobenzyl, parabromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl; R1 = R'1 = R2 = R'2; R1, R2, R'1 and R'2 are benzyl; R5 is an acetyl group; - R5 is a hydrogen atom; R4 is tert-butyldimethylsilyloxy at position f3; R4 is a trichloroacetimidate group (OC (NH) CCl3) in position a; R1 = R2 = R3 = R5 = H, R4 = OH and R'3 = Ac; the oligomer has a DP equal to 2, 3, 4, 5, 6, 7 or 8; the oligomer is in the form of an alternating copolymer, a random copolymer or a block copolymer. The oligomers according to the invention are in a pure form, that is to say that they are not in the form of a mixture of oligomers but in the form of a single oligomer of DP and DA given. The only impurities are compounds of low molecular weight, such as solvents used in the synthesis or purification and present at less than 1% by weight. The oligomers of formula (I), (Ia) and (Ib), and in particular dimers or trimers, in which the amine and the OH functions are in protected form, may in particular serve as an intermediate for the synthesis of other oligomers. The oligomers of formula (I), (Ia) and (Ib) in which R1 = R2 = R3 = R5 = H, R4 = -OH and R'3 = Ac may be directly used in biological or other applications.

  According to another of its aspects, the present invention proposes to provide monomers useful for the preparation of such oligomers. The invention therefore relates to a monomer of formula: OR "1 in which: - R" 1 and R "2 identical or different are protecting groups of alcohols, R" 3 represents a protective group of amines, for guiding the linkage (1-4), during a glycosidic coupling, in (3 and leading after deprotection to an -NH2 function, under conditions that would not modify another protected amine group capable of driving under other conditions of deprotection at a the group -NHAc, R "4 is a hydroxyl group in protected form, preferably in position [3, or a leaving group, preferably in the α-position, said leaving group being capable of forming an oxy-bridge according to a link f3- (1-4) with a free OHOH located in the 4-position of another glycosyl group, and R "5 is a hydrogen atom or a group protecting the alcohols According to preferred aspects, the oligomers according to the invention have one or the other of the features below when they do not exclude each other: R "3 is a dichloroacetyl, chloroacetyl or trichloroacetyl group or a -C (O) ORd group, with Rd chosen from benzyl groups, methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, parachlorobenzyl, 2,4-dichlorobenzyl, R "3 being preferably a benzyloxycarbonyl group, R" 5 is selected from the groups -C (O) Ra, with Ra = -CH3, - CH2Cl, -CHCl2, -CCI3, -CF3, -CH2OMe, -CH2OCPh3, -CH2OC6H4-p-Cl, -C (CH3) 3, -Ph, -C6H4 (p-MeO), -R "4 is selected from the groups -OSi (CH3) 2C (CH3) 3, -SOiPh2C (CH3) 3, -OC6H4-p-OMe, -OCH2CH = CH2, -OCH2CH2CH2CH = CH2, -SPh, -SEt, -OC (NH) CCI3, R 1 and R 2, which are identical or different, are chosen from benzyl, para-methoxybenzyl, para-nitrobenzyl, parabromobenzyl, para-chlorobenzyl and 2,4-dichlorobenzyl groups, R "1 and R" 2 represent a benzyl group; R "3 is a benzyloxycarbonyl group; R" 4 is a group preferably leaving in the α-position, said leaving group being capable of forming an oxy-bridge with a free -OH in the 4-position of another glycosyl group, and R Is a group protecting the alcohols, in particular R "4 is a group OOC (NH) CCl3 and R" is an acetyl group; R "4 is a hydroxyl group in protected form, preferably in position [3, and R "5 is a hydrogen atom or a group protecting the alcohols, in particular R" 4 is a tert-butyldimethylsilyloxy group in the [3. The invention also proposes to provide a process which makes it possible to prepare oligomers, and in particular hetero-oligomers of D-glucosamine and / V-acetyl-D-glucosamine, by controlling the size, the degree of acetylation and the architecture of the oligomers obtained. In this context, the subject of the present invention is a process for the preparation of dimers of formula: by coupling of the following monomers: in which: R11, R12, R'11 and R'12 represent, each independently, a group protecting the alcohols for example, selected from benzyl, para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl, -R13 and R'13 are each independently: an amine protecting group, for orienting the linkage (1, 4), during a glycosidic coupling, to R and leading after deprotection to an -NH 2 function, under conditions which do not modify a protected amine group capable of driving under other conditions of deprotection to a group -NHAc, for example selected from -C (O) ORd groups, with Rd selected from benzyl, para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl groups; e, R3 being preferably a benzyloxycarbonyl group, or an amine protecting group, for orienting the 1 (IV) (V) (1-4) bond, upon glycosidic coupling, to [3 and conducting after deprotection to an -NHAc function, under conditions which do not modify a protected amine group capable of leading, under other deprotection conditions, to a group -NH2, for example chosen from the dichloroacetyl, chloroacetyl and trichloroacetyl groups, -R14 is a leaving group, preferably in the α-position, said leaving group being capable of forming an oxy-bridge with a free OHOH located at the 4-position of another glycosyl group, for example chosen from the groups -SPh or -SEt at position [3, or preferably- OC (NH) CCI3, in position a, - R'14 is a group protecting the alcohols, preferably in position (3, for example chosen from the groups -OSi (CH3) 2C (CH3) 3, - OSiPh2C (CH3) 3, -OC6H4-p-OMe, -OCH2CH = CH2r -OCH2CH2CH2CH = C H2, -SPh and -SEt, and R15 is a group protecting the alcohols, for example chosen from -C (O) Ra groups, with Ra = -CH3, -CH2Cl, -CHCl2, -CCI3, -CF3, -CH2OMe , -CH2OCPh3, -CH2OC6H4-p-Cl, -C (CH3) 3, -Ph, -C6H4 (p-MeO). The subject of the present invention is also a process for the preparation of hetero-oligomer of controlled DP and DA comprising the following steps: a coupling, so as to form a 13- (1-4) bond, between a monomer or a donor oligomer of formula: Z10 R120. _16. (VI) and an acceptor monomer or oligomer of formula (VII) in which: R 11, R 12, R 11 and R 12 each independently represent a group protecting the alcohols, for example chosen from benzyl, para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl, -R16 and R'16 are each independently: an amine-protecting group for orienting the linkage ( 1-4), during a glycosidic coupling, at 0 and leading after deprotection to an -NH 2 function, under conditions which do not modify a protected amine group capable of leading under other deprotection conditions to a group -NHAc, for example, chosen from -C (O) ORd groups, with Rd chosen from benzyl, para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, para-chlorobenzyl and 2,4-dichlorobenzyl groups, R3 preferably being a benzyloxycarbonyl group; , or a protective group of amines, for orienting the linkage (1-4), during a glycosidic coupling, to 13 and leading after deprotection to a -NHAc function, under conditions that do not modify a protected amine group capable of driving in other deprotection conditions at a -NH2 group, for example chosen from dichloroacetyl, chloroacetyl and trichloroacetyl groups, R14 is a leaving group capable of forming an oxy bridge with a free OHOH located at the 4-position of another glycosyl group, for example chosen among the groups -SPh or ùSEt at position f3, or preferably -OC (NH) CCI3, at position a, Z1 represents a group protecting the alcohols, for example chosen from the groups -C (O) Ra, with Ra = - CH3, -CH2Cl, -CHCl2, -CCI3, -F CF3, -CH2OMe, -CH2OCPh3, -CH2OC6H4-p-Cl, -C (CH3) 3, -Ph, -C6H4 (p-MeO) or else Z1 represents a residue glycosyl of the formula -P1-Z3, linked by a p- (1-4) bond to the glycosyl unit of the compound (VI) Z2 represents a protecting group for alcohols, preferably in the 13-position, for example chosen from the groups -OSi (CH3) 2C (CH3) 3, -OSiPh2C (CH3) 3, -OC6H4-p-OMe, -OCH2CH = CH2, -OCH2CH2CH2CH = CH2r-SPh and -SEt, or Z2 represents a glycosyl residue of formula -P2-Z4, linked by a 13- (1-4) bond to the glycosyl unit of the compound (VII), - Z3 represents a group protecting the alcohols, for example chosen from -C (O) Ra groups, with Ra = -CH3, -CH2Cl, -CHCl2, -CCI3, -F CF3, -CH2OMe, -CH2OCPh3, -CH2OC6H4-p-Cl, -C (CH3) 3, - Ph, -C6H4 (p-MeO), Z4 represents a group protecting the alcohols, preferably in position 13, for example chosen from the groups -OSi (CH3) 2C (CH3) 3, -OSiPh2C (CH3) 3, -OC6H4 -p-OMe, -OCH2CH = CH2, -OCH2CH2CH2CH = CH2r-SPh and -SEt, -P1 and P2 are each independently constituted by one or more identical or different glycosyl units bonded to one another via a link 13 - (1ù4), and chosen from glucosamine units of formula: R17NH and the word IV-acetyl-D-glucosamine compounds of the formula: OR'11 in which R 11, R 18, R 11 and R 12 are as defined above for (VI) and (VII), and R 17 and R 17 represent each independently: a protecting group of the amines, for orienting the linkage (1, 4), during glycosidic coupling, to f3 and leading after deprotection to an -NH2 function, under conditions which do not modify a protected amine group capable of leading under other deprotection conditions to a group -NHAc, or a protecting group of the amines, which makes it possible to orient the linkage (1, 4), during a glycosidic coupling, to f3 and leading after deprotection to a function - NHAc, under conditions which do not modify a protected amine group capable of leading, under other deprotection conditions, to a group -NH2, as defined previously for R16 and R'16, deprotection of the amine functions to lead to the functions of NH2 and NH2c desired and deprotection of the functions OH, according to a multi-step strategy.

  The subject of the invention is also the variants of these processes as defined in claims 21 to 33. The preparation process according to the invention thus makes it possible to prepare, in a perfectly controlled manner, all the possible structures of pure oligomers consisting of And V-acetyl-D-glucosamine and D-glucosamine, with a degree of polymerization of between 2 and 8. The process according to the invention is particularly suitable for the production of oligomers derived from chitin and chitosan, that is, that is, involving two different motifs, β-acetyl-D-glucosamine and D-glucosamine. This process makes it possible to form a whole library of oligomers with perfectly controlled dimensions and architectures, as regards their composition and the position of the two constituent entities along the oligomeric chain. Indeed, the oligomers are prepared by multi-step chemical syntheses involving three phases. The first is the synthesis of four monomers, some of whose chemical functions are specifically protected, to act as donors or acceptors of N-acetyl-D-glucosamine or D-glucosamine. The second phase shows all the possible combinations of couplings between a donor and an acceptor of / V-acetyl-D-glucosamine or D-glucosamine leading to the production of so-called protected oligomers. Four different dimers are first prepared, then these dimers will serve as a building block, the couplings can then be made between a monomer and a dimer or two dimers, the only condition being to implement a donor (characterized by a leaving group IGL at position 1 of glycosyl) and an acceptor (characterized by a free -OH function at position 4 of glycosyl), and so on. The newly synthesized oligomers can be converted to acceptors or donors by simple chemical modifications, and then used as such for the preparation of oligomers of higher degrees of polymerization. Finally, the third phase consists in selectively eliminating the different protections of the chemical functions introduced during the first phase, in order ultimately to lead to the desired oligomers. The method according to the invention thus comprises three phases: 1 st phase: preparation of four elementary units o 2nd phase: coupling of the elementary units → 3rd phase: cleavage of the protective groups and obtaining of the oligomers Regardless of the size of the oligomers to be prepared a first step consists in preparing donor and acceptor monomers which will be used for the construction of the oligomers. Four monomers are required to perform all possible constructions. These monomers will subsequently be used as elementary units to prepare the first oligomers of DP 2, then of higher DP. Two of these monomers act as the donor and acceptor of N-acetyl-D-glucosamine, and the other two of donor and acceptor of D-glucosamine. Advantageously, four monosaccharide monomers are synthesized from a single common commercial molecule, D-glucosamine hydrochloride. These monomers are characterized by protective groups of very specific alcohol and amine functions. There are two types of protective groups, temporary and permanent. These groups are preferably chosen to meet various criteria such as ease of introduction / deletion, compatibility between them and their effectiveness in guiding the glycosidic coupling (1 → 4) in p. In a preferred manner, the protective groups of the alcohol functions are chosen from: - temporary protective groups: acetyl (Ac), benzylidene (PhCH), -C (NH) CCl 3, tert-butyldimethylsilyl (TBS) - permanent protective groups: benzyl (Bn). Preferably, the protective groups of the amine functional groups are chosen from trichioroacetyl (TCA) which, after deprotection, leads to the -NHAc group and the benzyloxycarbonyl (Z) which, after deprotection, leads to the -NH2 group. Other types of protection can, of course, be considered. The protection of the alcohol function at the 4 (4-OH) position may also be carried out in the form of an ester function (-OC (O) Ra), such that: Ra = -CH3: acetate ester o Ra = - CH2Cl = chloroacetate ester o Ra = -CHCl2: dichloroacetate ester o Ra = -CCI3: trichloroacetate ester o Ra = -CF3: trifluoroacetate ester o Ra = -CH2OMe: methoxyacetate ester o Ra = -CH2OCPh3: triphenylmethoxyacetate ester o Ra = -CH2OC6H4- p-Cl: p-chlorophenoxyacetate ester o Ra = (CH3) 3C-: pivaloate ester o R '= -Ph: benzoate ester o Ra = p-MeOC6H4-: p-methoxybenzoate ester Regarding the alcohol function in the anomeric position, it can still be protected in the form Rb: o Rb = -OSi (CH3) 2C (CH3) 3: t-butyldimethylsilyl ether, in beta position Rb = -OSiPh2C (CH3) 3: t-butyldiphenylsilyl ether, in beta position Rb = -OC6H4-p-OMe: p-methoxyphenyl ether, in beta position Rb = -OCH2CH = CH2: allyl ether, in beta position Rb = -OCH2CH2CH2CH = CH2: ether r of n-pentenyl, in beta position o Rb = -SPh: thiophenyl, in beta position o Rb = -SEt: thioethyl, in beta position o Rb = -OC (NH) CCI3, in position alpha It therefore appears that in the Within the scope of the invention, a hydroxyl function, in protected form, which designates a group which after deprotection leads to a function OH, may in particular be in the form of OR, but also of SR. The groups ûSPh, -SEt, and in particular -OC (NH) CCI3, may serve as a leaving group. The protection of the two alcohol functional groups at the 3 (3-OH) and 5 (5-OH) positions can also be carried out in the form of an ether function (-ORc), such as: o Rc = C6H4CH2-: benzyl group o Rc = p-MeOC6H4CH2-: para-methoxybenzyl group o Rc = p-NO2C6H4CH2-: para-nitrobenzyl group o Rc = p-BrC6H4CH2-: para-bromobenzyl group o Rc = p-CIC6H4CH2-: para-chlorobenzyl group o Rc = 2,4-Cl2C6H4CH2-: 2,4-dichlorobenzyl group The amine function (-NH2) can be protected as a carbamate function (-NHC (O) ORd), such that: o Rd = C6H4CH2 -: benzyl group o Rd = p-MeOC6H4CH2-: para-methoxybenzyl group o Rd = p-NO2C6H4CH2-: para-nitrobenzyl group o Rd = p-BrC6H4CH-2: para-bromobenzyl group o Rd = p-CIC6H4CH2-: group para-chlorobenzyl o Rd = 2,4-Cl2C6H4CH2-: 2,4-dichlorobenzyl group The acetamide function (-NHAc) can be protected in the form of an amide function (-NHRe), such as: o Re = CCI3CO- : trichloroacetyl group o Re = CHCl 2CO-: dichloroacetyl group o Re = CH2CICO-: chloroacetyl group For the methods of deprotection, reference may be made to TW Greene, PGM Wuts, protective groups in organic synthesis (3rd ed.), Edition Wiley & Sons, 1999, 779 pages . The description which follows, with reference to FIGS. 1-6, details the synthesis of the four protected monomers with these preferred protecting groups. Fig. 1 illustrates a synthesis of monomers derived from GlcNAc. Fig. 2 illustrates a synthesis of monomers derived from GlcN. Fig. 3 illustrates a synthesis of disaccharide GlcN-GlcNAc. Fig. 4 illustrates a synthesis of the disaccharide GlcN-GIcN. Fig. 5 illustrates a synthesis of the GIcNAc-GIcN disaccharide. Fig. Figure 6 illustrates a synthesis of the GIcNAc-GIcNAc disaccharide. The preparation of the acceptor and the donor of / If-acetyl-D-glucosamine follows a common multi-step reaction scheme given in FIG. 1 annexed. Firstly, the amine function of the hydrochloride of D-glucosamine is converted into a trichloroacetamide function by reaction with trichloroacetyl chloride in a basic medium. The hydroxyl functions are then acetylated under standard conditions (acetic anhydride / pyridine) without prior purification. The next two steps consist in protecting the anomeric position with a tertbutyldimethylsilyl group in position 13, firstly by reaction with hydrazine acetate in dimethylformamide, allowing the selective cleavage of the acetate function in position. 1, then by reaction of the hemiacetal intermediate with tert-butyldimethylsilyl chloride in the presence of imidazole in N, N-dimethylformamide. Thus, the hydrochloride of D-glucosamine is converted to compound 1 in four steps. Compound 1 then undergoes complete deacetylation in the presence of sodium methanolate in methanol. The hydroxyl functions in the 4 and 6 positions of the triol obtained after neutralization on acidic resin are protected by a benzylidene group by reaction with 2,2-dimethoxybenzaldehyde under acidic conditions, to yield compound 2 with a yield of 85% on both steps. The benzylation of the hydroxyl function at the 3-position with benzyl bromide in the presence of sodium hydride leads to the compound 3 with a yield of 73%. The reaction of the compound 3 with triethylsilane in the presence of trifluoroacetic acid causes the regioselective opening of the benzylidene ring at the 4-position and the obtention of the compound 4. This compound will act as an acceptor of / -acetyl-D-glucosamine in following the manufacturing process. The donor of N-acetyl-D-glucosamine (compound 5) is, for its part, synthesized from compound 4 in 3 steps. Firstly, the hydroxyl function at position 3 is acetylated by the acetic anhydride / pyridine mixture with a yield of 85%. The tertbutyldimethylsilyl group is then cleaved in the presence of tetrabutylammonium fluoride and acetic acid to give a hemiacetal intermediate, which is reacted with trichloroacetonitrile under basic conditions to yield the α-configuration imidate (compound 5). The two monomers which will act as acceptor (4 'compound) and D-glucosamine donor (5' compound) are synthesized according to a multi-step reaction scheme shown in FIG. 2 annexed. It is very similar to that described in the case of the synthesis of the two monomers of IV-acetyl-D-glucosamine. Two points differ, however. The first relates to the use of a novel amine protecting group, benzyloxycarbonyl (Z), introduced by reaction with benzyl chloroformate under basic conditions. The second concerns the reaction conditions of benzylation of the compound 2 '. Since the carbamate NH 2 function is sensitive to very basic conditions, the conventional method of O-benzylation (benzyl bromide / sodium hydride) can not be employed. The benzyl group was therefore introduced under mild basic conditions (benzyl bromide / barium oxide, barium hydroxide).

  The coupling of monomers consists in reacting an 'acceptor' monomer with a 'donor' monomer to yield a protected oligomer of DP 2. This reaction is advantageously carried out under anhydrous conditions and catalyzed by a Lewis acid, preferably trimethylsilyl trifluoromethanesulfonate (TMSOTf) or ethereal boron trifluoride (BF3.Et2O). By combining the acceptors and donors of N-acetyl-D-glucosamine and D-glucosamine, four different structures of protected oligomers are thus obtained, as mentioned in TABLE 1 below.

  TABLE 1 Acceptor Donor DISACCHARIDE OBn OC (NH) CCI3 OBn OTBS Aco OBn OTBS Aco OO 8n0 OBn BnO HO OO TCAHN BnO BnO TCAHN TCAHN compound 4 TCAHN compound 5 Compound 6d OBn OC (NH) CCI3 OBn OTBS ACO OBn OTBS Aco OO BnO OBn BnO HO OO TCAHN BnO BnO ZHN TCAHN compound 4 'ZHN compound 5 Compound 6c OBn OC (NH) CCI3 OBn OTBS Aco OBn OTBS OO BnO OBn Aco HO 0 BnO BnO BnO ZHN TCAHN ZHN compound 4 TCAHN compound 5' Compound 6a OBn OC ( ## STR1 ## Compound 4 has been described in particular by Melean L. et al. in Carbohydr. Res. 337 (21-23), 2002, 1893-1916 and by Ratner D. et al. in Org. Lett. 5 (24), 2003, 4717-4720 and Compound 5 by Ratner D. et al. in Org. Lett. 5 (24), 2003, 4717-4720. The preparation of compounds 6a, 6b and 6c is advantageously in the presence of BF 3 .Et 2 O, the preparation of compound 6d being advantageously in the presence of TMSOTf. In the context of the invention, once the desired oligomers of DP 2 or higher DP are obtained in protected form, this protected form comprising both specifically protected amine and alcohol functions, the last stages will consist of deprotect these said functions. Obtaining the target oligomers thus implies, in a last phase, to eliminate the different protections by employing specific reactions according to a multi-step strategy. Figs. 3 to 6 illustrate these deprotection steps in the case of compounds 6a, 6b, 6c and 6d respectively. In the case where the oligomer has NHTCA functions, the first step of deprotection consists in converting the trichloroacetamide functions, as a function of acetamide. This deprotection is carried out by reduction, advantageously using triethyltin hydride, in the presence of 2,2'-azobisisobutyronitrile (AIBN) in benzene. The acetyl group at the 4-position of the ring is then removed by reaction, in particular with a sodium methanolate / methanol mixture to give free hydroxyl. It is also possible to envisage deprotection under milder basic conditions (for example K 2 CO 3 / MeOH / H 2 O, guanidine / EtOH / CH 2 Cl 2, NEt 3 / MeOH / H 2 O), or even under acidic conditions (for example HCl sat / MeOH). The next step is to cleave the tertbutyldimethylsilyl protecting group from the hemiacetal function, preferably employing tetrabutylammonium fluoride in the presence of acetic acid in tetrahydrofuran. This deprotection is carried out with a yield of 88%. Finally, the deprotection of the functions OH, by the benzyl groups, can be carried out simultaneously with the deprotection of the functions NH 2, by palladium-carbon catalyzed hydrogenolysis. Since orthogonal protecting groups and selective deprotection reactions are used, the order of the deprotection steps can be modified and adapted to the chosen protecting groups. However, it is preferable to retain the hydrogenolysis step at the end of the synthesis. The method according to the invention therefore makes it possible, for each application envisaged, to prepare a given oligomer which will provide a selected biological response and may be used at a low dose. The method according to the invention therefore makes it possible to create the oligomers, in a manner, for each biological requirement, and thus to reduce the quantities employed, in particular in the case of elicitric properties. The possible applications of the oligomers according to the invention, and in particular those in unprotected form, concern the entire life sciences sector: pharmaceutical (active ingredients), biomedical (medical devices), food, cosmetics, dietetics, phytosanitary, food packaging. The following examples illustrate the invention and are not limiting in nature. All reagents and solvents were obtained from Aldrich and Acros. Reactions were followed by thin layer chromatography, using silica gel coated on aluminum plate (Merck 60 F254). The revelation was carried out by spraying an alcoholic solution of sulfuric acid (100/0 by volume in ethanol) followed by heating at 180 ° C. A UV revelation was also used for certain compounds. Purifications by chromatography were carried out on a column of silica gel (Merck Gerudan silica gel Si 60, 40-60 m). The NMR analyzes were carried out on a Brucker AC spectrometer, at 75 MHz for 13 C NMR and at 300 MHz for 1 H NMR. 2D NMRs and 13C NMRs were carried out by the NMR Center at Lyon 1 University. For the description of the 1H NMR spectra, the calibration of the chemical shifts is done by centering the residual peak of the water on 4.79 ppm, chloroform over 7.26 ppm and methanol over 3.31 ppm. Electrospray mass spectrometry (ES) analyzes were performed on a MicroMass-Waters LCT spectrometer by the CNRS Central Analysis Service in Vernaizon (69). The elementary analyzes were carried out by the CNRS Central Analysis Service in Vernaizon (69) on microanalysers of their design.

Compound 1 (3,4,6-Tri-O-acetyl-2-deoxy-10-tert-butyldimethylsilyl-2-trichloroacetamidof 3-D-glucopyranose Hydrazine acetate (4.7 g, 50.6 mmol ) is added to a solution of 1,3,4,6-tetra-acetyl-2-deoxy-2-trichloroacetamido-D-glucopyranose (16.2 g, 32.9 mmol) obtained according to Carbohydr Res., 1994, 260, 189-202, in anhydrous DMF (100 mL) The solution is stirred for 30 min at room temperature and then poured into ice water The organic phase is extracted with ethyl acetate (EtOAc , 3x250 ml), washed successively with water, saturated aqueous solution of NaHCO 3 and then with water, dried (MgSO 4), and concentrated under reduced pressure.

  A mixture containing the resulting hemiacetal, imidazole (9.0 g, 132.0 mmol), and tert-butyldimethylsilyl chloride (9.9 g, 65.9 mmol) in anhydrous DMF (120 mL) is stirred for 8 h at room temperature, then diluted in EtOAc (3x250 mL), washed successively with water, an aqueous solution of HCl (5%) and then water, dried (MgSO4), and concentrated.

  The residue is eluted on a silica gel chromatography column with Heptane-EtOAc (1: 1) and crystallized from EtOAc-Heptane to give Compound 1, as a white powder (11.0). g, 60% 2 steps); 1H NMR (300 MHz, CDCl3): δ 6.74 (d, 1H, J2, NH = 9.4 Hz, NH), 5.30 (dd, 1H, J3.4 = 9.2 Hz, 12.3). = 10.9 Hz, H-3), 5.09 (dd, 1H, J4.5 = 10.0 Hz, H-4), 4.88 (d, 1H, J1.2 = 7.9 Hz, H-1), 4.23 (dd, 1H, J5.6b = 5.7 Hz, J6a, 6b = 12.2 Hz, H-6b), 4.15 (dd, 1H, 15.6a = 2, 7 Hz, H-6a), 3.95 (m, 1H, H-2), 3.74 (m, 1H, H-5), 2.08 (s, 3H, CH3CO), 2.04 (s). , 3H, CH3CO), 2.03 (s, 3H, CH3CO), 0.88 (s, 9H, (CH3) 3CSi), 0.13 (s, 3H, CH3Si), 0.10 (s, 3H, CH 3 Si); 13C NMR (75 MHz, CDCl3): δ 171.30 (CO, Ac), 170.75 (CO, Ac), 169.44 (CO, Ac), 161.97 (CDNH), 95.89 (C, Ac); 1), 92.47 (CCl 3), 72, 13 (C-3), 71.81 (C-5), 68.92 (C-4), 62.58 (C-6), 57.96 ( C-2), 25.62 ((CH3) 3CSi), 20.86 (CH3CO), 20.84 (CH3CO), 20.79 (CH3CO), 17.96 ((CH3) 3CSi), -4.13 (CH3Si), -5.13 (CH3Si); ISMS m / z: 604, [M + K +], 588, [M + Na +], 434, [M-OTBDMS] + for 35Cl; Anal. Calc. for C20H32Cl3NO9Si: C, 42.52; H, 5.71; N, 2.49; found C, 42.89; H, 5.76; N, 2.42.

Compound 2,4,6-O-Benzylidene-2-deoxy-10-tert-butyldimethylsilyl-2-trichloroacetamido-3-D-glucopyranose A suspension of compound 1 (10.7 g, 18.9 mmol) in methanol (100 mL) ) is treated for 1 h at room temperature with NaOMe (1M, 3 mL). The solution is then neutralized using Amberlite IR-120 (H +) resin, filtered and concentrated to give the corresponding triol. Camphorsulfonic acid (88 mg, 0.4 mmol) was added to a solution containing triol and 2,2-dimethoxybenzaldehyde (3.4 mL, 22.6 mmol) in acetonitrile (120 mL). The solution is stirred for 1 h at room temperature. Triethylamine is added (160 L) and the solvent is evaporated under reduced pressure. The residue is eluted on a silica gel chromatography column with Heptane EtOAc (2: 1) to give compound 2 as a colorless oil (8.25 g, 83% from 1). ); 1H NMR (300 MHz, CDCl3): 7.65-7.36 (m, 5H, Ph), 6.94 (d, 1H, J2, NH 7.4 Hz, N / 1, 5.53 (s, 1H, PhCl, 5.09 (d, 1H, J1, 27.7 Hz, H-1), 4.31 (dd, 1H, -1s, 6eq 4.6 Hz, J6eq, 6ax 10.5 Hz, H-6eq), 4.26 (m, 1H, 13.4, 8.6 Hz, J2.3 10.1 Hz, H-3), 3.77 (dd, 1H, -15.6ax9.6 Hz ), 3.53-3.48 (m, 3H, H-4, H-5, H-2), 3.01 (si, 1H, O / + 3), 0.89 (s, 9H, ( CH3) 3CSi), 0.13 (s, 3H, CH3Si), 0.11 (s, 3H, CH3Si), 13C NMR (75 MHz, CDCl3): b 162.29 (COCCl3), 137.09 (aromatic C) ), 129.48 - 126.46 (aromatic CH), 102.01 (CHPh), 95.34 (C-1), 92.59 (CCl3), 81.73 (C-4), 69.74 ( C-3), 68.66 (C-6), 66.31 (C-5), 61.61 (C-2), 25.71 ((CH3) 3CSi), 17.94 ((CH3) 3CSi ), -4.04 (CH351), -5.04 (CH3Si), ISMS (maldi) m / z: 548.07 [M + Na +], Anal Calc for C21H30Cl3NO65I: C, 47.87; 5.74, N, 2.67, found C, 47.51, H, 5.53, N, 2.47.

Compound 3 3-O-Benzyl-4,6-O-benzylidene-2-deoxy-1-O-tert-butyldimethylsilyl-2-trichloroacetamido3-D-glucopyranose Sodium hydride (60% in mineral oil 1.2 g, 29.3 mmol) is added at 0 ° C. to a solution of compound 2 (7.4 g, 14.1 mmol) in anhydrous DMF (55 mL). The mixture is stirred for 30 minutes at this temperature. Benzyl bromide (2.2 mL, 18.4 mmol) is then added, and the mixture is stirred for 30 min at 0 ° C. and then for 90 min at room temperature. Methanol (5 mL) is added cautiously, then the mixture is diluted in EtOAc (400 mL), washed twice with water, dried (MgSO4) and concentrated. The residue is eluted on a silica gel chromatography column with Heptane-EtOAc (5: 1) and crystallized from EtOAc-Heptane to give Compound 3 as a white powder (6.4). g, 73%); 1H NMR (300 MHz, CDCl3): δ 7.53-7.27 (m, 10H, Ph), 6.86 (d, 1H, -NH 7.9 Hz, NH), 5.59 (s, 1H, PhCH), 5.18 (d, 1H, J, 2.7.9 Hz, H-1), 4.79 (ABq, 2H, C / 2Ph), 4.32 (dd, 1H, - , 6eq 4.9 Hz, J6eq, 6ax 10.6 Hz, H-6eq), 4.23 (m, 1H, J3.4 8.9 Hz, J2.3 10.3 Hz, H-3), 3 , 81 (dd, 1H, 15.6 x 10.2 Hz, H-6ax), 3.90 (dd, 1H, J4.5 9.6 Hz, H-4), 3.58-3.45 ( m, 2H, H-2, H-5), 0.91 (s, 9H, (C / 3) 3CSi), 0.11 (s, 3H, CH 3 Si), 0.09 (s, 3H, C) 3Si); 13C NMR (125 MHz, CDCl3): 8,161.83 (CDCCI3), 137.98, 137.35 (aromatic C), 129.18-126.15 (aromatic CH), 101.38 (CHPh), 95, (C-1), 92.58 (CCl 3), 82.84 (C-4), 75.79 (C-3), 74.75 (CH 2 Ph), 68.79 (C-6), 66, (C-5), 60.99 (C-2), 25.72 ((CH3) 3CSi), 17.95 ((CH3) 3CSi), - 4.07 (CH3Si), -5.06 (CH3Si) ); ISMS (maldi) m / r. 638.13 [M + Na +]; Anal. Calc. for C28H36Cl3NO6Si: C, 54.45; H, 5.88; N, 2.28; found C, 54.46; H, 5.97; N, 2.38.

  Compound 4 3,6-Di-O-benzyl-2-deoxy-10-test-butyldimethylsilyl-2-25-trichloroacetamido [β-D-glucopyranose A mixture consisting of compound 3 (17.4 g, 28.2 mmol), molecular sieve (3A) and triethylsilane (45 mL, 282 mmol) in anhydrous CH2Cl2 (250 mL) is cooled to 0 C. Trifluoroacetic acid (22 mL, 285 mmol) is added and the mixture is stirred for 1 h at 0 ° C. Triethylamine (3.3 ml) is added and the mixture is diluted in CH 2 Cl 2 (150 ml), washed successively with water, saturated aqueous NaHCO 3 solution and then with water. dried (MgSO4), and concentrated. The residue is eluted on a silica gel chromatography column with Heptane-EtOAc (5: 2) to give compound 4 as a colorless oil which crystallizes slowly. A white powder is obtained by crystallization of the residue in an EtOAc-heptane mixture (14.19 g, 81%); 1H NMR (300MHz, CDCl3): δ 7.35-7.24 (m, 10H, Ph), 6.98 (d, 1H, J2, NH8.1Hz, N / 1, 5.02 (d); , 1H, J, 27.9 Hz, H-1), 4.75 (ABq, 2H, CH2Ph), 4.56 (ABq, 2H, Ch Ph), 3.92 (dd, 1H, J3, 8.42 Hz, J2.3 10.5 Hz, H-3), 3.71-3.64 (m, 3H, H-4, H-6a, H-6b), 3.58-3, 48 (m, 2H, H-2, H-5), 2.95 (st, 1H, OH-4), 0.88 (s, 9H, (C / F 3) 3CSi), 0.12 (s, 3H, CH3Si), 0.09 (s, 3H, CH3Si), 13C NMR (125 MHz, CDCl3): b 161.78 (CDCCI3), 138.22, 137.78 (aromatic C), 128.73-127 , 84 (aromatic CH), 94.72 (C-1), 92.69 (CCl3), 79.69 (C-3), 74.60, 73.92 (CH2Ph), 73.79 (C-5), ), 73.65 (C-4), 70.84 (C-6), 60.41 (C-2), 25.78 ((CH3) 3CSi), 18.00 ((CH3) 3C5i), - 4.02 (CH3Si), -5.04 (CH3Si), ISMS (maldi) m / z 642.05 [M + Na +], Anal Calc for C28H38Cl3NO6Si: C, 54.33, H, 6.19 N, 2.26, found C, 54.53, H, 6.21, N, 2.16.

  Compound 5 4-O-Acetyl-3,6-di-O-benzyl-2-deoxy-2-trichloroacetamido-1-20 O-trichloroacetimidoyl-α-D-glucopyranose The acetylation conducted on compound 4 under standard conditions (Ac20 in pyridine), followed by concentration of the mixture under reduced pressure and crystallization of the residue in EtOAc-Heptane gives 4-O-acetyl-3,6-di-O-benzyl-2-deoxy-1-compound O-tertbutyldimethylsilyl-2-trichloroacetamido- (1D-glucopyranose (3.1 g, 95%); 1H NMR (300 MHz, CDCl3): 7.34-7.21 (m, 10H, Ph), 6.96 ( d, 1H, J2, NH 7.5 Hz, NH), 5.06 (d, 1H, J, 7.7 Hz, H-1), 5.06 (dd, 1H, J4.59, 8 Hz, -13.4 8.9 Hz, H-4), 4.60 (ABq, 2H, CH2Ph), 4.52 (s, 2H, CH2Ph), 4.29 (dd, 1H, J2,3 10.5 Hz, H-3), 3.67 (m, 1H, J5, 6b 4.8 Hz, J5.6a 4.8 Hz, H-5), 3.55 (d, 2H, J6a, 6b <0.5 Hz, H-6b, H-6a), 3.44 (m, 1H, H-2), 1.87 (s, 3H, CH3CO), 0.89 (s, 9H, (CH3 3CSi), 0.14 (s, 3H, CH3Si), 0.11 (s, 3H, CH3Si), 13C NMR (125 MHz, CDCl3): 8169.91 (CO, Ac), 161.87 (COCCl3) ), 138.00, 137.73 (Aromatic C), 128.62-127.78 (aromatic CH), 94.14 (C-1), 92.51 (CCI3), 77.15 (C-3), 74.16, 73.68 ( CH2Ph), 73.43 (C-5), 71.77 (C-4), 69.86 (C-6), 60.94 (C-2), 25.76 ((CH3) 3CSi), 21 , 01 (CH3CO), 17.99 ((CH3) 3CSi), -4.05 (CH3Si), -5.11 (CH3Si); ISMS (maldi) m / r. 682.15 [M + Na +]; Anal. Calc. for C30H40Cl3NO79: C, 54.50; H, 5.97; N, 2.13; found C, 54.09; H, 6.08; N, 2.16.

  A mixture comprising the above isolated compound (1.37 g, 2.1 mmol), acetic acid (145 L, 2.5 mmol) and Bu4NF.3H2O (785 mg, 2.5 mmol) in anhydrous THF (18 mL) is stirred at 0 C for 14 h. The mixture is concentrated, then diluted in EtOAc (60 mL), washed successively with water, saturated aqueous NaHCO 3 solution, then water, dried (MgSO 4), and concentrated. A mixture of the resulting hemiacetal, CCI3CN (2 mL, 20 mmol) and DBU (77 L, 0.5 mmol) in anhydrous CH2Cl2 (10 mL) is stirred for 1 h at 0 ° C and then concentrated. The residue is eluted on a silica gel chromatography column with Heptane EtOAc (5: 2) and Et3N (0.2%) to give compound 5 as a colorless oil (1.34 g). , 94%); 1H NMR (300 MHz, CDCl3): δ 8.77 (s, 1H, NH imidate), 7.35-7.27 (m, 10H, Ph), 6.60 (d, 1H, JJ, NH 8, 5 Hz, NH), 6.47 (d, 1H, J1.2 3.4 Hz, H-1), 5.38 (dd, 1H, J4.5 9.8 Hz, 73.4 9.6). Hz, H-4), 4.65 (ABq, 2H, CH 2 Ph), 4.51 (ABq, 2H, CH 2 Ph), 4.46 (m, 1H, J 2, 10.7 Hz, H 2), 4.06 (m, 1H, H-5), 4.03 (dd, 1H, H-3), 3.60 (dd, 1H, J5.6a 3.3 Hz, J6a, 6b, 10.8 Hz, H-6a), 3.56 (dd, 1H, 15.6b, 4.2Hz, H-6b), 1.96 (s, 3H, CH3CO); 13C NMR (75 MHz, CDCl3): b 169.40 (CO, Ac), 161.87 (COCCI3), 160.01 (C = NH), 137.66, 137.09 (aromatic C), 128.86 -127.90 (aromatic CH), 94.47 (C-1), 92.13 (CCl3 trichloroacetamido), 90.83 (CCI3 imidate), 76.09 (C-3), 73.72, 73.01 (CH 2 Ph), 72.26 (C-5), 70.00 (C-4), 68.54 (C-6), 53.50 (C-2), 20.95 (CH 3 CO); ES + MS m / r. 530, [M-CCI3CONH] +; Anal. Calc. for C26H26Cl16N2O7: C, 45.18; H, 3.79; N, 4.05; found C, 45.09; H, 3.84; N, 4,12.30 Compound 3,4,6-Tri-O-acetyl-2- (benzyloxycarbonyl) amino-2-deoxy-10-tert-butyldimethylsilyl [iD-glucopyranose Hydrazine acetate (9.8 g, 106 mmol) is added to a solution of 1,3,4,6-tetra-O-acetyl-2-benzyloxycarbonyl-2-deoxy-D-glucopyranose (33.6 g, 70 mmol) obtained from the hydrochloride commercial glucosamine in anhydrous DMF (130 mL). The solution is stirred for 30 min at room temperature and then poured into ice water. The organic phase is extracted with EtOAc (3 × 350 mL), washed successively with water, saturated aqueous NaHCO 3 solution and then with water, dried (MgSO 4) and concentrated under reduced pressure. A mixture containing the resulting hemiacetal, imidazole (14.3 g, 209 mmol), and tertbutyldimethylsilyl chloride (15.8 g, 105 mmol) in anhydrous DMF (120 mL) is stirred for 5 hours at room temperature. room temperature, then diluted in EtOAc (3x300 mL), washed successively with water, an aqueous solution of HCl (5%) and then water, dried (MgSO4), and concentrated. The residue is eluted on a silica gel chromatography column with Heptane EtOAc (2: 1) and crystallized from EtOAc-heptane to give compound 1 'as a white powder (23.2 g). 60% on both stages); 1H NMR (300 MHz, CDCl3): δ 7.39-7.29 (m, 5H, Ph), 5.21 (m, 1H, NH), 5.07-5.01 (m, 3H, H); 3, H-4, H-1), 4.98 (m, 2H, CH 2 O); 4.19 (dd, 1H, -15.6b = 5.8Hz, _6a, 6b = 12.1Hz, H-6b), 4.11 (dd, 1H,), 6a = 2.6Hz, H -6a), 3.68 (m, 1H, H-2), 3.57 (m, 1H, H-5), 2.07 (s, 3H, CH3CO), 2.02 (s, 3H, CH3CO) ), 1.97 (s, 3H, CH3CO), 0.86 (s, 9H, (CH3) 3CSi), 0.09 (s, 3H, CH3Si), 0.06 (s, 3H, CH3Si); 13C NMR (75 MHz, CDCl3): 8170.89 (CO, Ac), 170.78 (CO, Ac), 169.65 (CO, Ac), 155.81 (CDNH), 136.36 (aromatic C) ), 128.59, 128.24 (aromatic CH), 96.36 (C-1), 72.19 (C-3), 71.86 (C-5), 69.23 (C-4), 66.99 (CH 2 O), 62.64 (C-6), 58.16 (C-2), 25.61 ((CH 3) 3 Cl 5), 20.84 (CH 3 CO), 20.79 (CH 3 CO), 74 (CH3CO), 18.01 ((CH3) 3CSi), -4.23 (CH3Si), -5.29 (CH3Si); ISMS (maldi) m / r. 576.22, [M + Na +]; Anal. Calc. for C 26 H 39 NO 10 Si: C, 56.40; H, 7.09; N, 2.54; found C, 56.03; H, 7.05; N, 2.89.

  Compound 2 '4,6-O-Benzylidene-2- (benzyloxycarbonyl) amino-2-deoxy-1-O-tert-butyldimethylsilyl-3-D-glucopyranose A suspension of compound 1' (23.2 g, 42 mmol) in methanol (250 mL) is treated for 1 h at room temperature with NaOMe (1M, 5 mL). The solution is then neutralized using Amberlite IR-120 (H +) resin, filtered and concentrated to give the corresponding triol. Camphorsulfonic acid (395 mg, 1.7 mmol) was added to a solution containing triol and 2,2-dimethoxybenzaldehyde (7.6 mL, 50.6 mmol) in acetonitrile (260 mL). The solution is stirred for 18 h at room temperature. Triethylamine (240 L) is added and the solvent is evaporated under reduced pressure. The residue crystallizes from Heptane-EtOAc to give compound 2 'as a white powder (19.82 g, 91% from Compound 1); 1H NMR (300 MHz, CDCl3): δ 7.51-7.32 (m, 10H, Ph), 5.50 (s, 1H, PhC / -O, 5.08 (m, 2H, CH2O); , 99 (d, 1H, -H, NH 7.5 Hz, NH), 4.83 (m, 1H, H-1), 4.27 (dd, 1H, J5.6eq 4.9 Hz, J6eq, 6ax 10.4 Hz, H-6eq), 4.04 (m, 1H, H-3), 3.75 (dd, 1H, J5.6ax 10.2 Hz, H-6ax), 3.54 (dd , 1H, J4.5 9.2 Hz, J3 4.9.1 Hz, H-4), 3.46 (m, 1H, H-5), 3.34 (m, 1H, H-2), 3 , 18 (if, 1H, OH-3), 0.87 (s, 9H, (CH3) 3CSi), 0.09 (s, 3H, CH3Si), 0.06 (s, 3H, SMCi), 13C NMR (75 MHz, CDCl3): 8156.57 (CO2CH2PH), 137.26, 136.28 (aromatic C), 129.34-126.51 (aromatic CH), 100.71 (CHPh), 96.39 ( C-1), 81.59 (C-4), 70.94 (C-3), 68.75 (C-6), 67.15 C1-120, 66.34 (C-5), 60, 85 (C-2), 25.65 ((CH3) 3CSi), 17.99 ((CH3) 3CSi), -4.11 (CH3Si), -5.23 (CH3Si), ISMS (maldi) m / z 538.22 [M + Na +]; Anal Calc for C27H37NO7Si: C, 62.89; H, 7.23; N, 2.73; found C, 62.56; H, 7.33; N, 2.71.

  Compound 3 '3-O-Benzyl-4,6-O-benzylidene-2- (benzyloxycarbonyl) amino-2-deoxy-1-O-tert-butyldimethylsilyl-13-U-glucopyranose A solution of the compound 2' (7 33 g, 14.2 mmol) in anhydrous DMF (100 mL) is stirred for 7 h at room temperature in the presence of barium oxide (8.72 g, 56.9 mmol), barium hydroxide octahydrate. (2.36 g, 7.5 mmol) and benzyl bromide (2.2 mL, 18.5 mmol). Celite is added and the mixture is stirred for 30 minutes and then filtered. The residue is washed with EtOAc (3x100 mL). The organic phase is then successively washed with water, an aqueous solution of HCl (5%) and then water, dried (MgSO4), and concentrated. The residue is eluted on a silica gel chromatography column with Heptane-EtOAc (3: 1) to give compound 3 which crystallizes from Et2O-heptane (5.54 g, 64%); 1H NMR (300 MHz, CDCl3): δ 7.53-7.28 (m, 15H, Ph), 5.55 (s, 1H, PhCH), 5.15-5.05 (m, 4H, H- 1, CH2O, N /), 4.74 (ABq, 2H, CH2Ph), 4.29 (dd, 1H, 75.6eq 4.9Hz, J6eq, 6ax 10.5Hz, H-6eq), 4 , 08 (m, 1H, H-3), 3.79 (dd, 1H, J5.6ax 10.2 Hz, H-6ax), 3.71 (dd, 1H, J4.5, 9.4 Hz, 13.4 9.2 Hz, H-4), 3.47 (m, 1H, H-5); 3.22 (m, 1H, H-2), 0.86 (s, 9H, (CH3) 3CSi), 0.07 (s, 3H, C13Si), 0.04 (s, 3H, CH3Si) ; 13C NMR (75 MHz, CDCl3): 8155.72 (CD2CH2PH), 138.42, 136.52 (aromatic C), 129.08-126.19 (aromatic CH), 101.30 (CHPh), 95, 98 (C-1), 82.72 (C-4), 76.56 (C-3), 74.44 (CH 2 Ph), 68.91 (C-6), 66.79 (CH 2 O), 66, (C-5), 60.29 (C-2), 25.67 ((CH3) 3CSi), 18.02 ((CH3) 3CSi), -4.21 (CH3Si), -5.27 (CH3Si) ); ES + MS m / r 628, [M + Na +], 606, [M + 1] +; Anal. Calc. for C34H43NO7Si: C, 67.41; H, 7.15; N, 2.32; found C, 67.19; H, 7.36; N, 2.26.

  Compound 4 '3,6-Di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-1-O-25-tert-butyldimethylsilyl-13-D-glucopyranose A mixture comprising 3' (7.95 g) 13.1 mmol), molecular sieve 3 (5 g) and triethylsilane (21 mL, 132 mmol) in anhydrous CH2Cl2 (150 mL) was cooled to 0 ° C. Trifluoroacetic acid (10 mL, 130 mmol) is added and the mixture is stirred for 1 h at 0 ° C. Triethylamine (3 mL) is added and the mixture is diluted in CH2Cl2 (100 mL), washed successively with water, saturated aqueous NaHCO3r solution. then water, dried (MgSO4), and concentrated. The residue is eluted on a silica gel chromatography column with Heptane-EtOAc (5: 2) to give compound 4 as a colorless oil (5.97 g, 75%); 1H NMR (300 MHz, CDCl3): δ 7.41-7.25 (m, 15H, Ph), 5.08 (m, 2H, NH, H-1), 4.88 (m, 2H, C / 1); 120); 4.71 (ABq, 2H, CH 2 Ph), 4.57 (ABq, 2H, CH 2 Ph), 3.81 (m, 1H, H-3), 3.72 (d, 2H, J 6a, 6b, 4.9 Hz). , H-6a, H-6b), 3.66 (dd, 1H, 4.59.9 Hz, -13.4, 8.5Hz, H-4), 3.45 (m, 2H, H- 5, H-2), 2.95 (m, 1H, OH-4), 0.86 (s, 9H, (CH3) 3CSi), 0.08 (s, 3H, CH3Si), 0.05 (s, , 3H, CH3Si); 13C NMR (75 MHz, CDCl3): 8155.85 (CO2CH2PH), 138.52, 136.54 (aromatic C), 128.61-127.76 (aromatic CH), 95.60 (C-1), 80.51 (C-3), 74.14, 73.88 (CH 2 Ph), 73.76 (C-5), 73.05 (C-4), 70.80 (C-6), 66.83 (CH 2 O), 59.45 (C-2), 25.70 ((CH 3) 3 C Si), 18.05 ((CH 3) 3 C 5 1), -4.11 (CH 3 Si), -5.27 (CH 3 Si); ES + MS m / r. 630, [M + Na +], 608, [M + 1] +, 477, [M-OTBDMS] +; Anal. Calc. for C34H45NO7Si: C, 67.19; H, 7.46; N, 2.30; found C, 66.96; H, 7.57; N, 2.35.

  Compound 5 '4-O-Acetyl-3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-1-O-trichloroacetimidoyl-α-D-glucopyranose The acetylation conducted on the compound 4' (1 51 g, 2.48 mmol) under standard conditions (Ac 2 O in pyridine), followed by concentration of the mixture under reduced pressure and crystallization of the residue in EtOAc-Heptane gives 4-O-acetyl-3-compound. 6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-1-O-tert-butyldimethylsilyl-β-D-glucopyranose (1.47 g, 91%); 1H NMR (300 MHz, CDCl3): δ 7.37-7.16 (m, 15H, Ph), 5.06-4.97 (m, 5H, J4.5 9.3 Hz, J3 4 9.3 Hz, H-4, H-1, CH 2 O, NH), 4.55 (ABq, 2H, CH 2 Ph), 4.51 (s, 2H, CH 2 Ph), 4.05 (m, 1H, H-3), 3.60 (m, 1H, J5.6b, 4.5Hz, 15.6a 4.8Hz, H-5), 3.53 (d, 2H, J6a, 6b <0.5Hz, H-6b, H-6a), 3.25 (m, 1H, H-2), 1.87 (s, 3H, CH3CO), 0.87 (s, 9H, (CH3) 3CSi), 0.11 (s, 3H); , CH3Si), 0.07 (s, 3H, CH3Si); 13C NMR (125 MHz, CDCl3): 8 169.93 (CO, Ac), 155.75 (CO2CH2PH), 138.16, 136.49 (aromatic C), 128.64-127.69 (aromatic CH), 95.09 (C-1), 77.90 (C-3), 73.73, 73.62 (CH 2 Ph), 73.41 (C-5), 71.82 (C-4), 70.05 (C-6), 66.83 (CH2O), 59.93 (C-2), 25.70 ((CH3) 3CSi), 21.02 (CH3CO), 18.05 ((CH3) 3CSi), - 4.15 (CH 3 Si), -5.27 (CH 3 Si); ES + MS m / z. 673, [M + Na +], 519, [M-OTBDMS] +; Anal. Calc. for C36H47NO8Si: C, 66.54; H, 7.29; N, 2.16; found C, 66.65; H, 7.42; N, 2.21. A solution of Bu4NF.3H2O (1.1 g, 3.5 mmol) and acetic acid (200 L, 3.5 mmol) in anhydrous THF (8 mL) is added to a solution of the compound obtained above. (1.9 g, 2.9 mmol) in anhydrous THF (30 mL) and stirred for 7 h at room temperature. The mixture is concentrated, then diluted in EtOAc (30 mL), washed successively with water, saturated aqueous NaHCO 3 solution, then water, dried (MgSO 4), and concentrated. A mixture of the resulting hemiacetal, CCI3CN (2.9 mL, 28.9 mmol) and DBU (109 L, 0.73 mmol) in anhydrous CH2Cl2 (20 mL) is stirred for 1 h at room temperature, then concentrated. The residue is eluted on a silica gel chromatography column with Heptane-EtOAc (5: 2) and Et3N (0.2%) to give 5 'as a colorless oil (1, 87 g, 95%); 1H NMR (300 MHz, CDCl3): δ 8.69 (s, 1H, NH imidate), 7.35-7.19 (m, 15H, Ph), 6.37, (d, 1H, J1.2 3, 2 Hz, H-1), 5.31 (dd, 1H, J4.5 9.7 Hz, -73.4 9.7 Hz, H-4), 5.07 (m, 3H, CH 2 O, NH ), 4.67-4.45 (m, 4H, 2xCH2Ph), 4.26 (m, 1H, 32.3 10.2 Hz, J2, NH 10.2 Hz, H-2), 4.02 (m, 1H, J5.6b 6.8 Hz, J5.6a 6.8 Hz, H-5), 3.83 (t, 1H, H-3), 3.55 (m, 2H, H-6a) H-6b), 1.93 (s, 3H, CH3CO); 13C NMR (75 MHz, CDCl3):? 169.45 (CO, Ac), 160.28 (C = NH), 155.74 (CO2CH2PH), 138.09, 137.74, 137.50, 136.20. (Aromatic C), 128.59-127.77 (aromatic Cl-1), 95.72 (C-1), 91.00 (CCI3 imidate), 76.41 (C-3), 73.59, 73 , 03 (CH2Ph), 72.09 (C-5), 70.22 (C-4), 68.74 (C-6), 66.83 (CH2O), 53.53 (C-2), 93 (CH3CO); ES + MS m / z. 519 [MCCI3CONH] +; Anal. Calc. for C 32 H 33 Cl 3 N 2 O 8: C, 56.52; H, 4.89; N, 2.06; found C, 56.64; H, 4.92; N, 2.01.

  Compound 6a Tert-butyldimethylsilyl O- (4-O-acetyl-3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-3-D-glucopyranosyl) - (1, O4) -3, 6- di-O-benzyl-2-deoxy-2-trichloroacetamido (3-D-glucopyranoside) A mixture consisting of the 5 'donor (922 mg, 1.36 mmol), the acceptor 4 (560 mg, 0.9 mmol) ) and molecular sieve 3 in anhydrous CH 2 Cl 2 (20 mL) is stirred for 1 hour at room temperature under argon, BF 3 .Et 2 O (26 L, 0.21 mmol) is added, and the mixture is stirred for 3 h. L) is added and the mixture is filtered through Celite and then concentrated under reduced pressure The residue is eluted on a silica gel chromatography column with toluene-EtOAc (9: 1) containing Et3N (0.2%) to give the disaccharide 6a as a white foam (720 mg, 70%) 1H NMR (300 MHz, CDCl3): δ 7.45-7.22 (m, 25H, Ph), 6.91 (d, 1H, J2, NH 7.4 Hz, Nhb), 5.09-4.85 (m, 5H, CH2O, H-la, Nhb, H-1b), 4.97 (t, 1H, J3 , 4.9 Hz, H-4a), 4.70-4.41 (m, 6H, 3xC) H2Ph), 4.26 (ABq, 2H, CH2Ph), 4.07-3.90 (m, 2H, H-3b, H-3a), 3.70-3.25 (m, 9H, H-4b); , H-2b, H-2a, H-5a, H-5b, H-6a, H-6b, H-6a, H-6b), 1.82 (s, 3H, CH3CO), 0.88 (s). , 9H, (Ch) 3CSi), 0.14 (s, 3H, CH3Si), 0.08 (s, 3H, CH3Si); 13C NMR (75 MHz, CDCl3): 8170.24 (CO, Ac), 169.89 (CO2CH2Ph), 162.13 (COCCl3), 138.91, 138.83, 138.44, 138.41, 138 , 34 (aromatic C), 129.04-127.88 (aromatic CH), 100.02 (C-la), 95.10 (C-1b), 93.06 (CCI3), 79.10 (C-1), 3a), 78.28 (C-4b), 76.57 (C-3b), 75.57 (C-5a), 74.95, 74.72, 74.21, 73.95 (CH2Ph), 73 , 55 (C-5b), 72.27 (C-4a), 70.27 (C-6a), 68.44 (C-6b), 67.21 (CH 2 O), 60.10 (C-2b) , 58.33 (C-2a), 26.11 (CH3) 3CSi, 21.31 (CH3CO), 18.34 (CH3) 3CSi, -3.74, -4.65 (CH3Si); ES + MS m / z: 1159, [M + Na +], 1137, [M + 1] +, 1005, [MOTBDMS] +; Anal. Calc. for C58H69Cl13N2O13SI: C, 61.29; H, 6.12; N, 2.46; found C, 61.13; H, 6.45; N, 2.40.

  Compound 6b Tert-butyldimethylsilyl O- (4-O-acetyl-3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-13-D-glucopyranosyl) - (1 → 4) -3, 6-di-O-benzyl-2-benzyloxycarbonyl) amino-2-deoxy- [3-D-glucopyranoside A mixture of the 5 'donor (1.9 g, 2.8 mmol), the 4' acceptor ( 1.13 g, 1.86 mmol) and 3'-molecular sieve in anhydrous CH2Cl2 (38 mL) is stirred for 1h at room temperature under argon. BF3.Et20 (53 L, 0.42 mmol) is added, and the mixture is stirred for 3 h. Et3N (100 L) is added and the mixture is filtered through Celite and then concentrated under reduced pressure. The residue is eluted on a silica gel chromatography column with toluene-EtOAc (9: 1) containing Et3N (0.2%) to give the disaccharide 6b as a white foam (1.46). g, 70%); 1H NMR (300 MHz, CDCl3): δ 7.38-7.15 (m, 30H, Ph), 5.09-5.02 (m, 4H, CH 2 O), 5.00 (t, 1H, J 3, 4. 9.3 Hz, J4.5 9.3 Hz, H-4a), 4.85-4.40 (m, 10H, H-1a, NHa, Nhb, H-1b, 3xC / Ph), 4, 32 (ABq, 2H, Ch Ph), 3.95 (t, 1H, J3.4, 8.8 Hz, J2.3, 8.8 Hz, H-3b), 3.74-3.63 (m, 2H). , H-3a, H-4b), 3.52-3.25 (m, 8H, H-2b, H-2a, H-5b, H-5a, H-6a, H-6b, H-6a, H-6b), 1.88 (s, 3H, CH3CO), 0.87 (s, 9H, (CH3) 3CSi), 0.09 (s, 3H, CH3 Si), 0.04 (s, 3H, CH3 Si ); 13C NMR (125 MHz, CDCl3):? 169.78 (CO, Ac), 157.48, 155.75 (CO2CH2Ph), 138.96, 138.19, 138.08, 138.00, 136.60 ( Aromatic C), 128.70-127.29 (aromatic CH), 99.86 (C-1a), 95.61 (C-1b), 78.73 (C-4b), 78.62 (C-3b) ), 76.50 (C-3a), 74.40 (C-5b), 73.81, 73.60, 73.55, 73.26 (CH2Ph), 73.10 (C-5a), 71, 74 (C-4a), 69.82 (C-6b), 68.15 (C-6a), 66.74, 66.56 (CH 2 O), 59.17 (C-2b), 57.83 (C -2a), 25.66 (CH3) 3CSi, 20.88 (Cl-13CO), 17.98 (CH3) 3CSi, -4.21, -5.25 (CH3Si).

  Compound 6c Tert-butyldimethylsilyl O- (4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-trichloroacetamido-13-D-glucopyranosyl) - (1ù 4) -3,6-di- O-30 benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-5-D-glucopyranoside A mixture of the donor (1.2 g, 1.74 mmol), the acceptor 4 '(705 mg, 1 16 mmol) and 3'-molecular sieves in anhydrous CH 2 Cl 2 (30 mL) are stirred for 1 hour at room temperature under argon. BF3.Et20 (35 L, 0.28 mmol) is added, and the mixture is stirred for 3 h. Et3N (120 L) is added and the mixture is filtered through Celite and then concentrated under reduced pressure. The residue is eluted on a silica gel chromatography column with toluene-EtOAc (9: 1) containing Et3N (0.2%) to give the disaccharide 6c, as a white foam (958 mg, 73%); 1H NMR (300 MHz, CDCl3): δ 7.33-7.11 (m, 25H, Ph), 6.80 (d, 1H, J2, NH7.7 Hz, NH?), 5.05 (t, 1H, J3.4 9.7 Hz, J4.5 9.7 Hz, H-4a), 4.95 (s, 2H, Cl2O), 4.87 (d, 1H, J1.2, 8.3 Hz, H-1α), 4.76 (d, 1H, J2, NH 8.3 Hz, Nhb), 4.72 (d, 1H, J1.2, 8.4 Hz, H-1b), 4.65-4. , 43 (m, 6H, 3xCH2Ph), 4.28 (ABq, 2H, C / Ph), 4.03 (t, 1H, 33.4 8.9 Hz, J2.3, 8.9 Hz, H- 3b), 3.95 (dd, 1H, J2.3 10.4 Hz, H-3a), 3.63-3.50 (m, 4H, H-4b, H-5a, H-6a, H- 6b), 3.45-3.26 (m, 5H, H-2b, H-2a H-5b, H-6a, H-6b), 1.76 (s, 3H, CH 3 CO), 0.78 ( s, 9H, (CH3) 3CSi), -0.02 (s, 3H, CH3Si), -0.08 (s, 3H, CH3Si); 13 C NMR (125 MHz, CDCl3): S 169.78 (CO, Ac), 168.72 (CO2CH2Ph), 162.02 (COCCl3), 138.81, 138.19, 138.05, 137.59 (C aromatic), 128.58-127.45 (aromatic CH), 100.01 (C-1b), 98.19 (C-la), 92.51 (CCl3), 77.73 (C-4b), 76 , 16 (C-3a), 74.46 (C-3b), 73.95, 73.62 (CH 2 Ph), 73.39 (C-5b), 73.32, 72.30 (CH 2 Ph), 71, 81 (C-5a), 70.23 (C-4a), 69.62 (C-6b), 68.41 (C-6a), 66.63 (CH 2 O), 58.67 (C-2b), 49.56 (C-2a), 25.66 (CH3) 3CSi, 20.89 (Cl-13CO), 17.97 (CH3) 3CSi, -4.18, -5.22 (CH3Si); ES + MS m / z: 1159, [M + Na +], 1137, [M + 1] +, 1005, [M-OTBDMS] +; Anal. Calc. for C 58 H 16 Cl 3 N 2 O 13 Si: C, 61.29; H, 6.12; N, 2.46; found C, 61.35; H, 6.39; N, 2.41.

  Compound 6d Tert-butyldimethylsilyl O- (4-O-acetyl-3,6-dioxbenzyl-2-deoxy-2-trichloroacetamido-R-glucopyranosyl) - (1-4) -3, 6-di-O- benzyl-2-deoxy-2-trichloroacetamido-β-D-glucopyranoside A mixture consisting of donor 5 (390 mg, 0.56 mmol), acceptor 4 (233 mg, 0.38 mmol) and molecular sieve 3 (0 5 g) in anhydrous CH 2 Cl 2 (5 mL) is stirred for 1 h at room temperature under argon. TMSOTf (13 L, 0.07 mmol) is added, and the mixture is stirred for 2 h. Et3N (30 L) is added and the mixture is filtered through Celite and then concentrated under reduced pressure. The residue is eluted on a silica gel chromatography column with toluene-EtOAc (9: 1) containing Et3N (0.2%) to give the disaccharide 6d, which recrystallizes from EtOAc-Heptane (410 mg, 90%); 1H NMR (500 MHz, CDCl3): δ 7.39-7.21 (m, 20H, Ph), 6.87 (d, 1H, J2, NH 7.9 Hz, Nhb), 6.77 (d, 1H, J2, NH 7.7 Hz, NHa), 5.05 (t, 1H, J3.4, 9.3 Hz, J4.5 9.3 Hz, H-4a), 5.04 (d, 1H, 2.7% (7.5 Hz, H-1), 4.96 (d, 1H, J1.2, 8.3 Hz, H-1a), 4.73 (ABq, 2H, CH2Ph), 4.62 (b.p. ABq, 2H, CH2Ph), 4.57 (ABq, 2H, CH2Ph), 4.34 (ABq, 2H, CH2Ph), 4.14 (t, 1H, 73.4, 8.7 Hz, J2.3). , 7 Hz, H-3b), 4.05 (dd, 1H, -73.4 8.9 Hz, J2.3 10.4 Hz, H-3a), 4.01 (dd, 1H, J3.4 9.8 Hz, J4.5 8.3 Hz, H-4b), 3.67 (m, 2H, H-6a, H-6b), 3.57 (m, 1H, H-2a), 3, 52-3.42 (m, 4H, H-2b, H-5a, H-5b, H-6b), 3.55 (dd, 1H, J5.6a 5.3 Hz, J5.6b 10.7 Hz) , H-6b), 1.87 (s, 3H, CH3CO), 0.87 (s, 9H, (Ch) 3CSi), 0.11 (s, 3H, CH3Si), 0.07 (s, 3H, CH 3 Si); 13 C NMR (125 MHz, CDCl3): 5170.12 (CO, Ac), 162.22, 162.02 (COCCl3), 138.73, 138.45, 138.40, 137.88 (aromatic C), 128.97-128.02 (aromatic CH), 98.55 (C-1a), 94.93 (C-1b), 92.98, 92.81 (CCI3), 77.99 (C-3a), 77.97 (C-4b), 76.05 (C-3b), 74.96 (C-5b), 74.75, 74.54, 74.06 (CH 2 Ph), 73.84 (C-5a) , 73.73 (CH 2 Ph), 72.32 (C-4a), 70.07 (C-6a), 68.70 (C-6b), 60.27 (C-2b), 59.21 (C-4a), 2a), 26.07 (CH3) 3CSi, 21.27 (CH3CO), 18.29 (CH3) 3CSi, -3.76, -4.69 (CH3Si); ES + MS m / r. 1170, [M + Na +], 1016, [M-OTBDMS] +; Anal. Calc. for C52H62Cl6N2O12Si: C, 54.45; H, 5.45; N, 2.45; found C, 54.62; H, 5.38; N, 2.41.

  Compound 7a Tert-Butyldimethylsilyl O- (3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-β-D-glucopyranosyl) - (1-4) -2-acetamido-3,6-di O-benzyl-2-deoxy-β-D-glucopyranoside A mixture consisting of compound 6a (837 mg, 0.74 mmol), Bu3SnH (1.2 mL, 4.5 mmol) and AIBN (30 mg) in anhydrous benzene (16 mL) is stirred for 1 h at room temperature under argon, then heated for 2 h at 80C, cooled and concentrated. The residue is stirred in heptane (40 mL), and the crystals obtained are filtered. The residue is eluted on a silica gel chromatography column with heptane EtOAc (1: 1) to give the tert-butyldimethylsilyl compound O- (4-O-acetyl-3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy (3-D-glucopyranosyl) - (1-4) -2-acetamido-3,6-di-O-benzyl-2-deoxy- (3-D-glucopyranoside, which recrystallizes from the mixture CH2Cl2-heptane as a white powder (571 mg, 75%); 1H NMR (500 MHz, CDCl3): δ 7.39-7.16 (m, 25H, Ph), 5.74 (m, 1H, Nhb), 5.07 (m, 3H, CH 2 O, NH?), 5.03 (t, 1H, J3.49.1Hz, J4, 9.1Hz, H-4a), 4.93 (d, 1H, J 2, 6.6 Hz, H-1 b), 4.71 (ABq, 2H, CH 2 Ph), 4.59 (d, 1H, J 2, 8.8 Hz, H-1a). ), 4.52 (m, 2H, CH 2 Ph), 4.47-4.30 (m, 4H, 2xCb Ph), 3.99 (m, 1H, H-4b), 3.91 (t, 1H, J2.3 7.8 Hz, J3.4 7.8 Hz, H-3b), 3.70 (m, 1H, H-3a), 3.56 (m, 2H, H-6b, H-6a) , 3.53-3.37 (m, 6H, H-5a, H-6b, H-6a, H-5b, H-2b, H-2a), 1.89 (s, 3H, CH3CONH), 1 , 87 (s, 3H, Cl CO), 0.86 (s, 9H, (CH3) 3CSi), 0.09 (s, 3H, CffiSi), 0.07 (s, 3H, CM Si), 13C NMR, (125 MHz, CISC 3): 8170.12 (CO, Ac), 169.87 (CONH), 156.00 (CO2CH2Ph), 139.11, 138.31, 138.06, 137.92, 136.57 (aromatic C) , 128.66-127.47 (aromatic CH), 100.09 (C-la), 95.04 (C-1b), 78.63 (C-3a), 77.97 (C-3b), 76 , 13 (C-4b), 74.33 (C-5b), 73.73, 73.72, 73.71, 73.39 (CH 2 Ph), 73.20 (C-5a), 71.57 (C -4a), 69.82 (C-6b), 68.86 (C-6a), 66.96 (CH 2 O), 57.50 (C-2b), 55.94 (C-2a), 25.75. (CH3) 3CSi, 23.54 (CH3CONH), 21.02 (Cl-13CO), 18.06 (CH3) 3CSi, -4.15, -5.14 (CH3Si); ES + MS m / z. 1055, [M + Na +], 1033, [M + 1] +, 901, [M-OTBDMS] +; Anal. Calc. for C58H72N2O13Si: C, 67.42; H, 7.02; N, 2.71; found C, 67.94; H, 7.36; N, 2.68. A suspension of the compound obtained above (507 mg, 0.49 mmol) in methanol (20 mL) is treated for 4 hours at 0 ° C. at room temperature with NaOMe (1M, 0.6 mL). The solution is then neutralized using Amberlite IR-120 (H +) resin, filtered and concentrated. The residue is eluted on a silica gel chromatography column with heptane-EtOAc (1: 1) to give compound 7a as a white foam (460 mg, 95%); 1H NMR (300 MHz, CDCl3): δ 7.46-7.19 (m, 25H, Ph), 5.71 (si, 1H, Nhb), 5.07 (s, 2H, CH 2 O), 4.90. (d, 1H, J, 6.4 Hz, H-1b), 4.70 (ABq, 2H, CH 2 Ph), 4.73-4.35 (m, 8H, H-1α, Nhb, 3xCH 2 Ph). , 3.92 (t, 1H, J2.3 6.8 Hz, -13.4 6.8 Hz, H-3b), 3.84 (dd, 1H, J4.5 7.4 Hz, -4b), 3.68 (t, 1H, J2.3 9.1 Hz, 13.4.9.1 Hz, H-3a), 3.65-3.40 (m, 8H, H-2b, H -6b, H-6b, H-6a, H-4a, H-2a, H-6a, H-5b), 3.27 (m, 1H, J4.5 9.7 Hz, J5.6a 5.1 Hz, J5.6b 5.1 Hz, H-5a), 2.99 (si, 1H, OH-4), 1.89 (s, 3H, CH3CONH), 0.87 (s, 9H, (CH3) 3CSi), 0.12 (s, 3H, CH3Si), 0.07 (s, 3H, CH3Si); 13C NMR (125 MHz, CDCl3): S 170.14 (CONH), 156.24 (CO2CH2Ph), 139.04, 138.89, 138.16, 137.60, 136.60 (aromatic C), 128, 57-127.34 (aromatic CH), 100.48 (C-1α), 95.09 (C-1b), 80.92 (C-5b), 77.86 (C-4b), 75.20 ( C-3b), 74.26 (C-3a), 73.73, 73.72 (CH 2 Ph), 73.69 (C-4a), 73.38 (CH 2 Ph), 73.12 (C-5a), 70.94 (CH 2 Ph), 69.40 (C-6a), 69.03 (C-6b), 66.83 (CH 2 O), 56.89 (C-2a), 55.68 (C-2b), 25.70 (CH3) 3CSi, 23.39 (CH3CONH), 17.98 (CH3) 3CSi, -4.21, -5.17 (CH3Si); ES + MS m / r. 1013, [M + Na +], 991, [M + 1] +, 859, [M-OTBDMS] +; Anal. Calc. for C56H70N2O12Si: C, 67.85; H, 7.12; N, 2.83; found C, 67.62; H, 7.48; N, 2.70.

  Compound 7b Tert-Butyldimethylsilyl O- (3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy [iD-glucopyranosyl] - (1H4) -3,6-di-O-benzyl-2-benzyloxycarbonyl ) amino-2-deoxy- (3-D-glucopyranoside A suspension of compound 6b (1.42 g, 1.26 mmol) in methanol (30 mL) is treated for 4 hours at ambient temperature with NaOMe ( 1M, 0.6 mL) The solution is then neutralized using Amberlite IR-120 (H +) resin, filtered and concentrated The residue is eluted on a silica gel chromatography column with a heptane-EtOAc mixture (2M, 0.6 mL). 1), to give compound 7b as a white foam (1.08 g, 79%) 1H NMR (300 MHz, CDCl3): δ 7.38-7.16 (m, 30H, Ph) ), 5.10 (m, 2H, CH 2 O), 5.02 (s, 2H, CH 2 O), 4.83 - 4.50 (m, 10H, NH 4, NH 4, H-1a, H-1, 3xCH 2 Ph). , 4.39 (s, 2H, CH 2 Ph), 3.90 (t, 1H, J 2, 8.9 Hz, 13.4 8.9 Hz, H-3a), 3.73 (m, 1H, H-4b), 3.63 (t, 1H, 13.4, 8.7 Hz, J2.3, 8.7 Hz, H-3b), 3.54 (dd, 1H, Js, 6a, 4.8). Hz, J6a, 6b 9.9 Hz, H-6a), 3.44 (dd, 1H, J5, 6b, 1 Hz, J6a, 6b 9.9 Hz, H-6a), 3.42-3.30 (m, 3H, H-2b, H-2a, H-4a), 3.25 (m, 1H, J4 , 9.7 Hz, H-5a), 3.22-3.13 (m, 2H, H-6a, H-6b), 3.03 (m, 1H, H-5b), 2.66 (m.p. s, 1H, OH'4), 0.86 (s, 9H, (CH3) 3CSi), 0.08 (s, 3H, CH3Si), 0.04 (s, 3H, CH3Si). 13C NMR (125 MHz, CDCl3): 8,156.03, 155.90 (CO2CH2Ph), 138.94, 138.44, 137.98, 137.66, 136.58, 136.50 (aromatic C), 128 , 47-127.09 (aromatic CH), 100.32 (C-1a), 95.65 (C-1b), 81.19, 78.86, 78.66, 76.38, 76.38, 76 , 22, 74,32, 73,90, 73,45, 73,31, 73,21, 70,68, 68,12, 66,55, 58,81, 57,14 (C-2, C-3 , C-4, C-5, C-6, OCH2Ph), 25.57 (CH3) 3CSi, 17.85 (CH3) 3CSi, -4.27, -5.30 (CH3Si).

  Compound 7c Tert-butyldimethylsilyl O- (2-acetamido-3,6-di-O-benzyl-2-deoxy- [1D-glucopyranosyl] - (1-4) -3, 6-di-O-benzyl-2 - (benzyloxycarbonyl) amino-2-deoxy- (3-U-glucopyranoside) A mixture consisting of compound 6c (792 mg, 0.7 mmol), Bu3SnH (1.1 mL, 4.1 mmol) and AIBN (30 mg). mg) in anhydrous benzene (15 mL) is stirred for 1 h at room temperature under argon, then heated for 2 h at 80C, cooled and concentrated, the residue is stirred in heptane (40 mL), and The crystals obtained are filtered and the residue is eluted on a silica gel chromatography column with a heptane-EtOAc mixture (1: 1) to give the tert-butyldimethylsilyl compound O- (2-acetamido-4O-acetyl-3,6). 1-Di-O-benzyl-2-deoxy- (3-n-glucopyranosyl) - (1-4) -3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-β-D-glucopyranoside as a white foam (592 mg, 82%) 1H NMR (500 MHz, CDCl3): δ 7.35-7.05 (m, 25H, Ph), 5.15 (d, 1H, J2) , NH 7.5 Hz, NHa), 4.96 (s, 2H, CH 2 O), 4.94 (t, 1H, .33.4, 9.6 Hz, J4.5, 9.6 Hz, H-4a), 4.81 (d, 1H, J 2, 8.3 Hz, H-1a). ), 4.80-4.40 (m, 8H, 3xCH2Ph, H-1b, Nhb), 4.25 (ABq, 2H, CHHPh), 3.91 (m, 2H, H-3b, H-3a) , 3.57 (m, 2H, H-4b, H-5a), 3.42-3.26 (m, 7H, H-6b, H-6b, H-6a, H-6a, H-5b, H-2b, H-2a), 1.78 (s, 3H, CH3CONH), 1.66 (s, 3H, CH3CO), 0.77 (s, 9H, (CH3) 3CSi), 0.12 (s). , 3H, CH3Si), 0.07 (s, 3H, Ch Si); 13 C NMR (125 MHz, CDCl 3): 8170.55 (CO, Ac), 169.95 (CONH), 155.70 (CO2CH 2 Ph), 138.91, 138.34, 138.19, 136.61 (C aromatic), 128.60-127.41 (aromatic CH), 99.21 (C-1a), 95.73 (C-1b), 78.56 (C-3b), 78.40 (C-3a) , 74.59 (C-4b), 74.40 (C-5b), 73.68 (C-5a), 73.57, 73.54, 73.37 (CH2Ph), 73.12 (C-4a) ), 71.98 (CH 2 Ph), 69.81 (C-6a), 68.60 (C-6b), 66.62 (Cl-120), 58.88 (C-2b), 57.37 (C-2a), ), 25.68 (CH3) 3CSi, 23.52 (CH3CONH), 20.99 (CH3CO), 18.02 (CH3) 3CSi, -4.17, -5.24 (CH3Si); ES + MS m / r. 1055, [M + Na +], 1033, [M + 1] +, 901, [M-OTBDMS] +; Anal. Calc. for C58H72N2O13Si: C, 67.42; H, 7.02; N, 2.71; found C, 67.82; H, 7.35; N, 2.59. A suspension of the compound obtained above (681 mg, 0.66 mmol) in methanol (20 mL) is treated for 4 hours at 0 ° C. at room temperature with NaOMe (1M, 0.5 mL). The solution is then neutralized using Amberlite IR-120 (H +) resin, filtered and concentrated. The residue is eluted on a silica gel chromatography column with heptane-EtOAc (1: 1) and to give 7c, which crystallizes from EtOAc-heptane, as a white powder (614). mg, 87%); 1H NMR (500 MHz, CDCl3): δ 7.39-7.21 (m, 25H, Ph), 5.05 (s, 2H, CH2O), 4.90 (d, 1H, J2, NH 7.9 Hz, NHa), 4.85 (m, 1H, Nhb), 4.82 (d, 1H, J1.2, 8.8 Hz, H-1a), 4.72 (ABq, 2H, CH2Ph), 4, 70 (ABq, 2H, CH2Ph), 4.63 (d, 1H, J1, 7.9Hz, H-1b), 4.60 (ABq, 2H, CH2Ph), 4.43 (s, 2H, CH2Ph); ), 3.94 (t, 1H, J2.3, 8.7 Hz, J3, 48.7 Hz, H-3b), 3.82 (m, 1H, H-3a), 3.69 (t, 1H, J3.4 8.8 Hz, J4.5 8.8 Hz, H-4a), 3.65 (dd, 1H, J5.6b 2.8 Hz, J6a, 6b 8.2 Hz, H-6b ), 3.60-3.49 (m, 4H, H-6b, H-6a, H-4b, H-2a), 3.47 (dd, 1H, J5.6a, 6.4 Hz, J6a, 6b). 9.6 Hz, H-6a), 3.44 (m, 1H, H-5b), 3.33 (m, 1H, J4.5 10.1 Hz, J5.6b 4.0 Hz, H-5a). ), 3.29 (m, 1H, H-2b), 3.12 (si, 1H, OH-4), 1.75 (s, 3H, CH3CONH), 0.86 (s, 9H, (CH3) 3CSi), 0.11 (s, 3H, CH3Si), -0.03 (s, 3H, C / Si); 13C NMR (125 MHz, CDCl3): 3170.18 (CONH), 155.70 (CO2CH2Ph), 139.03, 138.78, 138.21, 137.59, 136.61 (aromatic C), 128, 74-127.36 (aromatic CH), 100.01 (C-1α), 96.53 (C-1b), 81.10 (C-4b), 77.36 (C-3a), 76.70 ( C-3b), 74.61 (C-4a), 74.51, 74.03 (CH 2 Ph), 73.90 (C-5b), 73.83, 73.66 (CH 2 Ph), 72.70 (C -5a), 71.49 (C-6a), 68.70 (C-6b), 66.70 (C1-120), 59.15 (C-2b), 56.05 (C-2a), 73 (CH3) 3CSi, 23.63 (CH3CONH), 18.07 (CH3) 3CSi, -4.13, -5.20 (CH3Si); ES + MS m / z: 1013, [M + Na +], 991, [M + 1] +, 859, [M-OTBDMS] +; Anal. Calc. for C56H70N2O12Si: C, 67.85; H, 7.12; N, 2.83; found C, 67.70; H, 7.27; N, 2.73.

  Compound 7d Tert-butyldimethylsilyl O- (2-acetamido-3,6-di-O-benzyl-2-deoxy-fi-D-glucopyranosyl) - (1 + 4) -2-acetamido-3,6-di-O- benzyl-2-10 deoxy-β-D-glucopyranoside A mixture consisting of compound 6d (690 mg, 0.6 mmol), Bu3SnH (1.9 mL, 7.2 mmol) and AIBN (30 mg) in benzene Anhydrous (17 mL) is stirred for 1 h at room temperature under argon, then heated for 2 h at 80C, cooled and concentrated. The residue is stirred in heptane (40 mL), and the resulting crystals are filtered. The residue is eluted on a silica gel chromatography column with heptane-EtOAc (1: 1) to give the tert-butyldimethylsilyl compound O- (2-acetamido-4-O-acetyl-3,6-di- O-benzyl-2-deoxy-R-glucopyranosyl) (1-4) -2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside, which crystallizes from EtOAc-Heptane (592 mg, 82%); 1H NMR (500 MHz, CDCl3): δ 7.35-7.19 (m, 20H, Ph), 5.98 (si, Nhb), 5.21 (d, 1H, J2, NH 7.9 Hz, NHa), 5.07 (t, 1H, J3.49.1 Hz, J4.59.1Hz, H-4a), 4.92 (d, 1H, J, 6.33Hz, H -lb), 4.74 (d, 1H, J1.2 7.3 Hz, H-la), 4.70 (ABq, 2H, CH2Ph), 4.61 (ABq, 2H, C21HP), 4.57 (ABq, 2H, CH2Ph), 4.41 (ABq, 2H, 25 C /, Ph), 4.04 (t, 1H, J3.4, 6.8 Hz, J2.3, 6.8 Hz, H-3b), 3.95-3.90 (m, 2H, H-3a, H-4b), 3.78 (dd, 1H, J5.6a 4.7 Hz, J6a, 6b, 10.4 Hz, H-6a), 3.70-3.65 (m, 2H, H-6a, H-2b), 3.64-3.56 (m, 2H, H-2a, H-5a), 3.53. -3.49 (m, 2H, H-6b, H-5b), 3.44 (dd, 1H, J5.6b 6.3 Hz, J6a, 6b 11.7 Hz, H-6b), 1.88 (s, 3H, CH3CONH), 1.86 (s, 3H, CH3CONH), 1.75 (s, 3H, CH3CO), 0.83 (s, 9H, (CH3) 3CSi), 0.08 (s, 3H, CH3Si), 0.06 (s, 3H, Cf Si); 13C NMR (125 MHz, CDCl3): b 170.68 (CO, Ac), 170.22, 169.91 (CONH), 138.93, 138.37, 138.05, 137.99 (aromatic C), 128.65-127.49 (aromatic Cl-1), 99.54 (C-la), 95.15 (C-1b), 78.31 (C-4b), 77.82 (C-3a), 77.36 (C-3b), 74.99 (C-5a), 74.58 (C-5b), 73.69, 73.46, 73.18, 72.80 (CH 2 Ph), 71.72 ( C-4a), 69.73 (C-6a), 69.41 (C-6b), 56.51 (C-2a), 55.76 (C-2b), 25.73 (CH 3) 3CSi, 23 , 60, 23.47 (CH3CONH), 21.03 (CH3CO), 18.04 (CH3) 3CSi, -4.20, -5.16 (CH3Si); ES + MS m / z: 963, [M + Na +], 941, [M + 1] +, 809, [M-OTBDMS] +; Anal. Calc. for C52H68N2O12Si: C, 66.36; H, 7.28; N, 2.98; found C, 66.52; H, 7.06; N, 2.90. A suspension of the compound obtained above (738 mg, 0.78 mmol) in methanol (20 mL) is treated for 4 hours at 0 ° C. at room temperature with NaOMe (1M, 1 mL). The solution is then neutralized using Amberlite IR-120 (H +) resin, filtered and concentrated. The residue is eluted on a silica gel chromatography column with heptane-EtOAc (1: 2) to give compound 7d as a white foam (585 mg, 83%); 1H NMR (300 MHz, CDCl3): δ 7.40-7.19 (m, 20H, Ph), δ5.95 (d, J2, NH, 8.7 Hz, Nhb), 4.84 (d, 1H, J2, NH8.7Hz, Nha), 4.79 (d, 1H, J2, 5.7Hz, H-1b), 4.65 (ABq, 2H, CH2Ph), 4.62 (ABq, 2H, CH 2 Ph), 4.56 (d, 1H, J1.2 8.8 Hz, H-1a), 4.45-4.35 (m, 4H, 2xC /, Ph), 3.88 (t, 1H, .J3.4 6, 0 Hz, J2.3 6.0 Hz, H-3b), 3.73 (t, 1H, J3.4 6.2 Hz, J2.3 6.2 Hz, H- 3a), 3.72-3.54 (m, 7H, H-4a, H-4b, H-6a, H-6b, H-2b, H-2a, H-5b), 3.50 (dd, 1H, J5.6b 5.9 Hz, J6a, 6b 9.7 Hz, H-6b), 3.38 (dd, 1H, J5.6a 8.5 Hz, J6a, 6b 10.6 Hz, H-6a ), 3.26 (dd, 1H, 15.6a 4.7 Hz, J4.5 9.4 Hz, H-5a), 3.02 (si, 1H, 0 / 1-4), 1.91 ( s, 3H, Cf3 CONH), 1.83 (s, 3H, Ch3CONH), 0.86 (s, 9H, (Ch3) 3CSi), 0.12 (s, 3H, Ch3Si), 0.10 (s, , 3H, C / 13Si); ES + MS m / r. 921, [M + Na +], 899, [M + 1] +, 767, [M-OTBDMS] +; Anal. Calc. for C50H66N2O11Si: C, 66.79; H, 7.40; N, 3.13; found C, 67.44; H, 7.80; N, 3.01.

  Compound 8a (2-Amino-2-deoxy-β-D-glucopyranosyl) - (4α) -2-acetamido-2-deoxy-3-D-glucopyranose A mixture consisting of compound 7a (469 mg, 0.47 mmol), Acetic acid (68 L, 1.2 mmol) and Bu4NF.3H2O (383 mg, 1.2 mmol) in anhydrous THF (20 mL) was stirred at room temperature for 16 h. The mixture is concentrated, then diluted in EtOAc (30 mL), washed successively with water, saturated aqueous NaHCO3r solution and then water, dried (MgSO4), and concentrated. The residue is eluted on a silica gel chromatography column with CH 2 Cl 2 -MeOH (9: 1) to give the compound (3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy- [α-D-glucopyranosyl] (1-4) -2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranose as a white powder (370 mg, 89%); 1H NMR (500 MHz, MeOD): δ 7.45-7.22 (m, 25H, Ph), 5.11 (m, 2H, CH2 O), 5.10 (d, 1H, J1.2 3.4 Hz, H-1b), 4.80 (ABq, 2H, CH 2 Ph), 4.70-4.50 (m, 4H, 2xCH 2 Ph), 4.61 (d, 1H, J 2, 8.2 Hz, H-la), 4.37 (ABq, 2H, CH2Ph), 4.12 (dd, 1H, J2.3, 10.4, H-2b), 4.04 (t, 1H, J4.5 8.8 Hz, J3.4, 8.8 Hz, H-4b), 4.00 (m, 1H, H-3a), 3.81 (dd, 1H, J3.4, 8.5 Hz, H-3b), 3 , 76 (dd, 1H, J5.6b 1.7 Hz, J6a, 6b 11.2 Hz, H-6b), 3.72 (m, 1H, H-6a), 3.60-3.47 (m , 4H, H-4a, H-2a, H-6a, H-5a), 3.43 (dd, 1H, J5.6a 6.1 Hz, H-6b), 3.32 (m, 1H, H -5b), 1.97 (s, 3H, CH3CONH); 13C NMR (125 MHz, MeOD): 8 173.97 (CONH), 159.32 (CO2CH2Ph), 141.85, 140.91, 140.67, 140.46, 139.21 (aromatic C), 130, 33-128.86 (aromatic CH), 102.88 (C-1a), 93.28 (C-1b), 84.68 (C-4b), 80.49 (C-3b), 78.45 (C-1b), C-3a), 78.02 (C-5b), 76.78, 75.96, 75.34, 74.94 (CH2Ph), 73.27 (C-5a), 72.29 (C-4a) , 71.51 (C-6a), 70.60 (C-6b), 68.22 (CH 2 O), 59.76 (C-2a), 55.39 (C-2b), 23.53 (CH 3 CONH) . A solution of the compound obtained above (226 mg, 0.26 mmol) in a mixture of AcOEt-MeOH-H 2 O (5: 10: 4, 10 mL) is hydrogenated in the presence of 10% Pd-C (100 mg) during 48 h at room temperature. The mixture is filtered on celite. The residue is then eluted with water on a LH-20 chromatography column and then lyophilized to give compound 8a (73 mg, 0.19 mmol); 1H NMR (500 MHz, D 2 O): δ 5.15 (d, 1H, J 2, 2.2 Hz, H-lab), 4.64 (d, 1H, J 2, 7.9 Hz, H). -Wb), 4.43 (d, 1H, J, 27.9 Hz, H-1a), 3.90 (m, 1H, H-3b), 3.87-58 (m, 8H, H). -2b, H-4b, H-5ab, H-6ab); 3.46-3.28 (m, 2H, H-4a, H-3a), 2.62 (m, 1H, H-2a), 2.05 (s, 3H, CH3NHCO); 13 C NMR (125 MHz, D 2 O):? 175.10, 174.83 (CONH), 102.84 (C-1?), 95.19 (C-113b), 90.87 (C-lab), 78, 99, 78.60, 76.54, 75.78, 75.75, 75.06, 72.71, 70.47, 70.32, 69.92, 69.49, 60.97, 60.63, 60.53, 57.03, 56.72, 54.20 (C-2, C-3, C-4, C-5, C-6), 22.55, 22.26 (CH3CONH).

  Compound 8b (2-Amino-2-deoxy-β-D-glucopyranosyl) - (4α) -2-amino-2-deoxy-R-glucopyranose A mixture consisting of compound 7b (502 mg, 0.52 mmol), Acetic acid (67 L, 1.16 mmol) and Bu4NF.3H2O (366 mg, 1.16 mmol) in anhydrous THF (20 mL) was stirred at room temperature for 16 h. The mixture is concentrated, then diluted in EtOAc (30 mL), washed successively with water, saturated aqueous NaHCO 3 solution, then water, dried (MgSO 4), and concentrated. The residue is eluted on a silica gel chromatography column with CH 2 Cl 2 -MeOH (9: 1) to give the compound (3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy- α-D-glucopyranosyl) (1 - 4) -3,6-di-O-benzyl-2-benzyloxycarbonyl) amino-2-deoxy- (3-o-glucopyranose), in the form of a white powder (385 mg, 86%) 1H NMR (500 MHz, CDCl3): 7.41-7.14 (m, 30H, Ph), 5.27 (m, 1H, H-1b), 5.20-4. , (M, 10H, 4xCff 2 Ph, NHa, Nhb), 4.28 (d, 1H, h 2 7.9 Hz, H-1a), 4.02 (m, 1H, H-4b), 3.88 (m, 2H, H-2b, H-3b), 3.75-3.58 (m, 2H, H-3a, H-6a), 3.52 (m, 1H, H-6b), 3, 50-3.33 (m, 4H, H-2a, H-4a, H-6a, H-6b), 3.25 (m, 1H, H-5b), 3.19 (m, 1H, H- 5a); 13C NMR (125 MHz, CDCl3): δ 156.32, 156.31 (CD2CH2Ph), 139.27, 138.61, 137.90, 137.59, 136.66, 136.50 (aromatic C ), 129.16-127.19 (aromatic CH), 100.79 (C-1a), 92.84 (C-1b), 77.82 (C-5a), 77.12 (C-3b), 74.57 (C-3a), 74.35, 74.18, 73.80, 73.52 (CH 2 Ph), 72.86 (C-4a), 72.45 (C-5b), 71.52 ( C-6b), 70.31 (C-4b), 67.72 (C-6a), 67.43 (C1-120); ), 66.91 (CH 2 O), 55.84 (C-2b), 54.82 (C-2a). Compound 8b is prepared following the experimental protocol described for compound 8a.

  Compound 8c (2-Acetamido-2-deoxy-3-D-glucopyranosyl) - (1-4) -2-amino-2-deoxy-R-glucopyranose A mixture consisting of compound 7c (480 mg, 0.48 mmol), Acetic acid (69 L, 1.2 mmol) and Bu4NF.3H2O (382 mg, 1.2 mmol) in anhydrous THF (20 mL) was stirred at room temperature for 16 h. The mixture is concentrated, then diluted in EtOAc (30 mL), washed successively with water, saturated aqueous NaHCO 3 solution, then water, dried (MgSO 4), and concentrated. The residue is eluted on a silica gel chromatography column with CH2Cl2-MeOH (9: 1) to give the compound (2-acetamido-3,6-di-O-benzyl-2-deoxy- (3- D-glucopyranosyl) - (1-4) -3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-5-o-glucopyranose as a white powder (369 mg, 87%) 1H NMR (500 MHz, MeOD): δ 7.42-7.21 (m, 25H, Ph), 5.19 (d, 1H, J1.2, 8.9 Hz, H-1b), , 14 (ABq, 2H, CH2O), 4.90 (ABq, 2H, CH2Ph), 4.83 (ABq, 2H, CH2Ph), 4.80 (d, 1H, J1.28, 2 Hz, H- la), 4.68 (ABq, 2H, CH 2 Ph), 4.47 (ABq, 2H, CH 2 Ph), 4.11 (dd, 1H, J 2, 7.9 Hz, -3.4 9.9 Hz, H-3a), 4.07 (dd, 1H, J2.3 8.2 Hz, J3.4 10.1 Hz, H-3b), 3.91 (m, 6H, H-2b, H-2a, H-4a, H-6a, H-6b, H-6b), 3.60 (m, 2H, H-4a, H-5b), 3.49 (dd, 1H, J5.6a, 6.0Hz, J6a, 6b 11.0 Hz, H-6a), 3.39 (m, 1H, H-5b), 1.98 (s, 3H, CH3CONH), 13C NMR (125 MHz, MeOD): δ 174.19 (CONH), 159.45 (CD2CH2Ph), 141.68, 141.06, 140.75, 140.57, 139.11 (aromatic C), 130.25-128.83 (aromatic CH), 102.27 (C-Ia), 93.74 (C-1b), 84, 67 (C-4a), 80.56 (C-4b), 78.21 (C-3a), 78.15 (C-5a), 76.52, 76.10, 75.34, 75.07 ( CH 2 Ph), 73.32 (C-3b), 72.46 (C-5b), 71.46 (C-6b), 70.83 (C-6b), 68.30 (CH 2 O), 58.21 (C C-2a), 57.55 (C-2b), 23.99 (CH3CONH). Compound 8c is prepared following the experimental protocol described for compound 8a.

Compound 8d (2-Acetamido-2-deoxy-RD-glucopyranosyl) - (1--4) -2-acetamido-2-deoxy-α, β-D-glucopyranose A mixture consisting of compound 7d (556 mg, 0.62 mmol ), acetic acid (92 L, 1.5 mmol) and Bu4NF.3H2O (490 mg, 1.5 mmol) in anhydrous THF (23 mL) is stirred at room temperature for 16 h. The mixture is concentrated, then diluted in EtOAc (30 mL), washed successively with water, saturated aqueous NaHCO 3 solution, then water, dried (MgSO 4), and concentrated. The residue is eluted on a silica gel chromatography column with CH2Cl2-MeOH (9: 1) to give the compound (2-acetamido-3,6-di-O-benzyl-2-deoxy- (3- D-glucopyranosyl) - (1-4) -2-acetamido-3,6-di-O-benzyl-2-deoxy-α-oglucopyranose as a white powder (434 mg, 89%); 1H NMR (300 MHz, MeOD): δ 7.41-7.18 (m, 20H, Ph), 5.09 (d, 1H, J 2, 3.5 Hz, H-1), 5.00 ( ABq, 2H, CH2Ph), 4.76 (ABq, 2H, CH2Ph), 4.72 (d, 1H, J1.2 8.5 Hz, H-1a), 4.63 (ABq, 2H, CH2Ph), 4.40 (ABq, 2H, CH 2 Ph), 4.13 (dd, 1H, J 2, 10.4 Hz, H-2b), 4.05 (m, 2H, H-3a, H-4b), 3 , 85-3.70 (m, 5H, H-2a, H-3b, H-6a, H-6b, H-6b), 3.55 (m, 2H, H-4a, H-5a), 3 , 45 (dd, 1H, J5.6a 6.1 Hz, J6a, 6b 11.7 Hz, H-6b), 3.35 (m, 1H, H-5b), 1.92 (s, 3H, CH3CONH ), 1.91 (s, 3H, CMCONH); 13C NMR (75 MHz, MeOD): 8 174.18, 174.02 (CDNH), 141.81, 141.03, 140.69, 140.53 ( Aromatic C), 130.24-128.88 (aromatic CH), 102.33 (C-1a), 93.27 (C-1b), 84.68 (C-4b), 80.05 (C-3b) ), 79.62 (C-5b), 78.09 (C-3a), 76.51, 75.88, 75.3 4.75.07 (CH 2 Ph), 73.29 (C-5a), 72.56 (C-4a), 71.46 (C-6a), 70.77 (C-6b), 58.11 (C -2b), 55.42 (C-2a), 24.03, 23.54 (CH3CONH). Compound 8d is prepared following the experimental protocol described for compound 8a.

Claims (33)

  1 - Oligomer of formula (I): R5-P-R4 in which P consists of at least two glycosyl units chosen from glucosamine units of formula: R20 R3NH linked together by a 13- (1-4) bond, wherein: R1, R2, R'1 and R'2 each independently represent a hydrogen atom or an alcohol protecting group; R3 and R'3 each independently represent: an amine protecting group, for directing the linkage (1-4), during a glycosidic coupling, to [3 and leading after deprotection to an -NH 2 function, under conditions which do not modify a protected amine group capable of driving into other deprotection conditions to a group - NHAc, or an amine protecting group, for orienting the linkage (1-4), upon glycosidic coupling, to [3 and leading after deprotection to a function -NHAc under conditions which do not modify a protected amine group capable of in other deprotection conditions to a group - NH2, - or R3 and R'3 each independently represent a hydrogen atom or an acetyl group, it being understood that at least R3 or and the N-acetyl- D-glucosamine of formula: OR'1 R '20 R'3NHR'3 is different from the acetyl group, R4 is a hydroxyl group, or a hydroxyl group in protected form preferably in position [3, or a leaving group preferably in position a, said leaving group being capable of forming an oxy bridge according to a linkage [3- (1--4) with a free OHOH located in position 4 of another glycosyl group, and R5 is a hydrogen atom or a protective group of alcohols.   2- oligomer according to claim 1 of formula: R20 or O R'20 R5 (Ib) in which: - the glycosyl units are bonded to each other by a bond 13- (1ù4) - R1, R2, R'1, R ' 2, R3, R'3, R4 and R5 are as defined in claim 1; n and m are each independently 1, 2, 3, 4, 5, 6 or 7 and p is 1, 2; , 3 or 4, with the proviso that p * (n + m) is less than or equal to 8.   3- Oligomer according to claim 2, characterized in that n = m = p = 1.   4. Oligomer according to one of claims 1 to 3, characterized in that R3 = H and R'3 = Ac.   5-Oligomer according to one of claims 1 to 4, characterized in that: - R3 is -C (O) ORd, with Rd selected from benzyl, para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl, R3 being preferably a benzyloxycarbonyl group, R'3 is a dichloroacetyl, chloroacetyl, or preferably trichloroacetyl group.   6. Oligomer according to one of claims 1 to 5, characterized in that -R5 is selected from -C (O) Ra groups, with Ra = -CH3, -CH2Cl, -CHCl2, -CCI3, -CF3, -CH2OMe, -CH2OCPh3, -CH2OC6H4-p-C1, -C (CH3) 3, -Ph or -C6H4 (p-MeO), -R4 is selected from the groups -OSi (CH3) 2C (CH3) 3, - OSiPh2C (CH3) 3, -OC6H4-p-OMe, -OCH2CH = CH2i -OCH2CH2CH2CH = CH2, -Sph, -SEt, -OC (NH) CCI3, 10 -R1, R'1, R2 and R'2, identical or different, are selected from benzyl, para-methoxybenzyl, para-nitrobenzyl, parabromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl.   7- Oligomer according to one of claims 1 to 6, characterized in that R1 = R2 = R'1 = R'2. 15   8-Oligomer according to one of claims 1 to 7, characterized in that R1, R2, R'1 and R'2 represent a benzyl group.   9- Oligomer according to one of claims 1 to 8 characterized in that R5 is an acetyl group or a hydrogen atom.   10- Oligomer according to one of claims 1 to 9, characterized in that R4 is a tert-butyldimethylsilyloxy group in position [3 or a group -OC (NH) CCI3 in position a.   11- Oligomer according to one of claims 1 to 10, characterized in that R1 = R2 = R3 = R5 = H, R'3 = Ac and R4 = OH.   12. An oligomer according to claim 1 selected from: tert-butyldimethylsilyl O- (4-O-acetyl-3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-pn-glucopyranosyl) - (1) 4) -3,6-di-O-benzyl-2-deoxy-2-trichloroacetamido-13-D-glucopyranoside Tert-butyldimethylsilyl O- (4-O-acetyl-3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-p-glucopyranosyl) - (1-4) -3,6-di-O-30-benzyl-2-benzyloxycarbonyl) amino-2-deoxy-β-D-glucopyranoside Tert- Butyldimethylsilyl O- (4α-acetyl-3,6-di-O-benzyl-2-deoxy-2-trichloroacetamido-13-D-glucopyranosyl) - (1-4) -3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-13-D-glucopyranoside Tert-butyldimethylsilyl O- (4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-trichloroacetamido-pn-glucopyranosyl) - ( 1- (4) -3,6-di-O-benzyl-2-deoxy-2-trichloroacetamido-pD-glucopyranoside Tert-butyldimethylsilyl O- (3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino -2-Deoxy (3-D-glucopyranosyl) - (1 - * 4) -2-acetamido-3,6-di-O-benzyl-2-deoxy-3-D-glucopyranoside Tert-bu tyldimethylsilyl O- (4-O-acetyl-3,6-di-O-benzyl-2- (benzyl) wcarbonyl) amino-2-deoxy-β-D-glucopyranosyl) - (1-4) -2-acetamido-3 6-DiO-benzyl-2-deoxy-3-D-glucopyranoside Tert-butyldimethylsilyl O- (3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-33-D-glucopyra nosyl) - (1-4) -3,6-Di-O-benzyl-2-benzyloxycarbonyl) mid-2-deoxy-33-D-glucopyranoside Tert-butyldimethylsilyl O- (2-acetamido-3,6-di) O -benzyl-2-deoxy) - (3-D-glucopyranosyl) - (1H) -3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-3-D- glucopyranoside Tert-butyldimethylsilyl O- (2-acetamido-4-O-acetyl-3,6-di-O-benzyl-2-deoxy-3-n-glucopyranosyl) (1 - * 4) -3,6-di O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-3-D-glucopyranoside Tert-butyldimethylsilyl O- (2-acetamido-3,6-di-O-benzyl-2-deoxy-3-D-gi ucopyranosyl) - (1-a4) -2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside Tert-butyldimethylsilyl O- (2-acetamido-4-O-acetyl-3,6- di-O-benzyl-2-deoxy-3-D-giucopyranosyl) (1 - * 4) -2-acetamido-3,6-di-O-benzyl 1-2-deoxy-3-D-glucopyranoside (2-Amino-2-deoxy) -13-Dg l ucopyra nosyl) - (1 - * 4) -2-acetamido-2-deoxy- (3-D) Glucopyranose (3,6-Di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-F3-D-glucopyranosyl) - (1-4) -2-acetamido-3,6-di-O 2-amino-2-deoxy-α-D-glucopyranose (2-Amino-2-deoxy-β-D-glucopyranosyl) - (1-4) -2-amino-2-deoxy (3-D-glucopyranose (3.6 g) -Di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy- [3-D-glucopyranosyl) (1-4) -3,6-di-O-benzyl-2-benzyloxycarbonyl) amino-2- deoxy-β-N-glucopyranose (2-Acetamido-2-deoxy-3-D-glucopyranosyl) - (1-4) -2-amino-2-deoxy- (3-D-glucopyranose (2-acetamido-3 6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl) - (1-4) -3,6-di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-3 -D-glucopyranose (2-acetamido-3,6-di-O-benzyl-2-deoxy-3-D-glucopyranosyl) - (1-4) -2-acetamido-3,6-di-O-benzyl -2-deoxy-D-glucopyranose.   13- Monomer of formula: in which: R "1 and R" 2 identical or different are protecting groups of alcohols, - R "3 represents a group protecting the amines, to guide the connection (1-4), when a glycosidic coupling, in (3 and leading after deprotection to an -NH2 function, under conditions which would not modify another protected amine group capable of driving under other deprotection conditions to a group -NHAc, - R "4 is a hydroxyl group in protected form, preferably in the 3-position, or a leaving group, preferably in the α-position, said leaving group being capable of forming an oxy-bridge according to a P- (1-4) bond with a free OHOH located in position 4 of another glycosyl group, andR "5 is a hydrogen atom or an alcohol protecting group.   14 - Monomer according to claim 13, characterized in that: - R "3 is a dichloroacetyl, chloroacetyl or trichloroacetyl group or a -C (O) ORd group, with Rd chosen from benzyl and para-methoxybenzyl groups, nitrobenzyl, para-bromobenzyl, parachlorobenzyl, 2,4-dichlorobenzyl, R "3 being preferably a benzyloxycarbonyl group, R" 5 is chosen from the groups -C (O) Ra, with Ra = -CH3, -CH2Cl, -CHCl2 , -CCI3, -CF3, -CH2OMe, -CH2OCPh3, -CH2OC6H4-p-Cl, -C (CH3) 3, -Ph, -C6H4 (p-MeO), R "4 is chosen from the groups -OSi ( CH 3) 2 C (CH 3) 3, - OSiPh 2 C (CH 3) 3 R -OC 6 H 4 -p-OMe, -OCH 2 CH = CH 2, -OCH 2 CH 2 CH 2 CH = CH 2, - SPh, -SEt, -OC (NH) CCI 3, R "1 and R" 2, which may be identical or different, are chosen from benzyl, para-methoxybenzyl, para-nitrobenzyl, parabromobenzyl, para-chlorobenzyl and 2,4-dichlorobenzyl groups.   15 - Monomer according to claim 13 or 14, characterized in that R "1 and R" 2 represent a benzyl group.   16 - Monomer according to one of claims 13 to 15, characterized in that R "3 is a benzyloxycarbonyl group.   17 - Monomer according to one of claims 13 to 16, characterized in that R "4 is a group preferably leaving in position a, said leaving group being capable of forming an oxy bridge with a free OHH located in position 4 of another glycosyl group, and R "5 is a protecting group for alcohols.   18 - Monomer according to claim 17, characterized in that R "4 is a group -OC (NH) CCI3, in position a and R" 5 is an acetyl group.   19 - Monomer according to one of claims 13 to 18, characterized in that R "4 is a group protecting the alcohols, preferably at position 13, preferably a tert-butyldimethylsilyloxy group, and R" 5 is a d hydrogen or a protecting group of the alcohols.   The monomer according to claim 13, selected from: 3,6-Di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-1-O-tert-butyldimethylsilyl-β-n-glucopyranose 4-O-acetyl -3,6-Di-O-benzyl-2- (benzyloxycarbonyl) amino-2-deoxy-1-O-5-trichloroacetimidoyl-α-D-glucopyranose   21 - Process for the preparation of dimers of formula: by coupling of the following monomers: in which: R 11, R 12, R 11 and R 12 each independently represent a group protecting the alcohols, for example chosen from benzyl groups; , para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl, - R13 and R'13 each independently represent: • an amine-protecting group, for orienting the linkage (1- 4), during a glycosidic coupling, at f3 and leading after deprotection to a function -NH2, under conditions which do not modify 14 R, 14 (V) not a protected amine group capable of driving under other conditions of deprotection to a group -NHAc, for example selected from -C (O) ORd groups, with Rd selected from benzyl, para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl, R3 preferably being a group be nzyloxycarbonyl, or an amine protecting group, for orienting the linkage (1-4), upon glycosidic coupling, to [3 and leading after deprotection to a -NHAc function, under conditions which do not modify an amine moiety protected compound which may lead, under other deprotection conditions, to an NH 2 group, for example chosen from dichloroacetyl, chloroacetyl and trichloroacetyl groups, R 14 is a leaving group, preferably in the α-position, said leaving group being capable of forming a bridge oxy with a free ioOH located in position 4 of another glycosyl group; R 14 is, for example, chosen from the groups -SPh or ùSEt at position 13, or preferably - OC (NH) CCI 3, at position a, - R '14 is a group protecting the alcohols, preferably at position 13, for example chosen among the groups -OSi (CH3) 2C (CH3) 3, -OsiPh2C (CH3) 3, -OC6H4-p-OMe, -OCH2CH = CH2, -OCH2CH2CH2CH = CH2, -SPh and -SEt, and R15 is a group protecting the alcohols, for example selected from -C (O) Ra groups, with Ra = -CH3, -CH2Cl, -CHCl2, -CCI3, -CF3, -CH2OMe, -CH2OCPh3r -CH2OC6H4-p-Cl, -C ( CH3) 3, -Ph, -C6H4 (p-MeO).   22 - Process according to claim 21 characterized in that R13 and / or R'13 represent a benzyloxycarbonyl group.   23 - Process according to claim 21 characterized in that R13 and / or R'13 represent a trichloroacetyl group.   24 - Method according to one of claims 21 to 23 characterized in that R14 represents a group ùOC (NH) CCI3, in position a.   25 - Process according to one of claims 21 to 24 characterized in that: R'14 represents the tert-butyldimethylsilyloxy group, R15 represents an acetyl group, - R11, R'11, R12 and R'12 represent a benzyl group.   26 - Method according to one of claims 21 to 25 characterized in that the coupling is carried out in the presence of a Lewis acid, under anhydrous conditions, preferably in the presence of TMSOTf or BF3.Et2O.   A process for the preparation of controlled DP and DA hetero-oligomer comprising the following steps: a coupling, so as to form a [3- (1--4) bond, between a donor monomer or oligomer of formula (VI) and an acceptor monomer or oligomer of formula (VII) in which: - R11, R12, R'11 and R'12 represent, each independently, a group protecting the alcohols, for example chosen from benzyl groups , para-methoxybenzyl, para-nitrobenzyl, para-bromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl, - R16 and R'16 each independently represent: • an amine-protecting group for orienting the linkage (1 -4), during a glycosidic coupling, in p and leading afterdeprotection to an -NH 2 function, under conditions which do not modify a protected amine group capable of driving under other deprotection conditions to a group -NHAc, for example selected from -C (0) ORd groups, with Rd selected from benzyl, para-methoxybenzyl, para-nitrobenzyl, parabromobenzyl, para-chlorobenzyl, 2,4-dichlorobenzyl, R3 being preferably a benzyloxycarbonyl group, or an amine protecting group, for orienting the linkage (1u4), during a glycosidic coupling, in [3 and leading after deprotection to a function -NHAc, under conditions which do not modify a protected amine group capable of driving under other deprotection conditions to a group -NH2, for example, chosen from dichloroacetyl, chloroacetyl and trichloroacetyl groups, R14 is a leaving group capable of forming an oxy-bridge with a free OHOH situated at the 4-position of another glycosyl group, for example chosen from the groups -SPh or -SEt in position [3, or preferably - OC (NH) CCI3, in position a, - Z1 represents a group protecting the alcohols, for example chosen from the groups -C (O) Ra, with Ra = -CH3, -CH 2CI, -CHCl2, -CCI3, -CF3, -CH2OMe, -CH2OCPh3, -CH2OC6H4-p-C1, -C (CH3) 3, -Ph, -C6H4 (p-MeO) or else Z1 represents a glycosyl residue of formula -P1-Z3, linked by a p- (1-4) bond to the glycosyl unit of the compound (VI) - Z2 represents a group protecting the alcohols, preferably in position 13, for example chosen from the groups -OSi (CH3) 2C ( CH 3) 3, -OSiPh 2 C (CH 3) 3 R -OC 6 H 4 -p-OMe, -OCH 2 CH = CH 2, -OCH 2 CH 2 CH 2 CH = CH 2, - SPh and -SEt, or Z 2 represents a glycosyl residue of formula P 2 -Z 4, linked by a linkage (3- (1-4) to the glycosyl unit of the compound (VII), - Z3 represents a group protecting the alcohols, for example selected from the groups -C (O) Ra, with Ra = -CH3, -CH2Cl, -CHCl2, - CCI 3, - CF 3, -CH 2 OMe, -CH 2 OCPh 3 R -CH 2 OC 6 H 4 -p-Cl, -C (CH 3) 3, -Ph, -C 6 H 4 (p-MeO), - Z 4 represents a group protecting the alcohols, preferably in position f 3, for example, chosen from the group -OSi (CH 3) 2 C (CH 3) 3, - OSiPh 2 C (CH 3) 3, -OC 6 H 4 -p-OMe, -OCH 2 CH = CH 2, -OCH 2 CH 2 CH 2 CH = CH 2, - SPh and -SEt, - P1 and P2 are each independently constituted by one or more identical or different glycosyl units linked together by a 13- (1û4) bond, and chosen from glucosamine units of formula: OR11 R17NH and the units / acetyl-D-glucosamine of formula: OR'11 0 R'120 R'17NH in which R11, R12, R'11 and R'12 are as defined previously for (VI) and (VII), and R17 and R '17 each independently represent: an amine protecting group for orienting the linkage (1-4), upon glycosidic coupling, to [3] and leading after deprotection to an -NH 2 function, under conditions which do not modify a protected amine group capable of leading, under other deprotection conditions, to a group --NHAc, - or an amine-protecting group, which makes it possible to orient the link (1-4), during a glycosidic coupling, to f3 and leading after deprotection to a function -NHAc, under conditions which do not modify not a protected amine group capable of leading, under other deprotection conditions, to a -NH 2 group, as defined previously for R16 and R'16, deprotection of the amine functional groups to give the desired -NH 2 and NH 4c functions and deprotection oOH functions, according to a multi-step strategy.   28 - Process according to claim 27 characterized in that R16 or R'16 and, optionally, R17 and / or R'17 represent a benzyloxycarbonyl group or a trichloroacetyl group.   29 - Process according to claim 27 or 28 characterized in that R11, R'11, R12 and R'12 represent a benzyl group.   30 - Process according to one of claims 27 to 29 characterized in that R14 is a group ùOC (NH) CCI3.   31 - Method according to one of claims 27 to 30 characterized in that Z1 represents an oligomer, -P1-Ac, with P1 as defined in claim 25 and Z2 represents a oligomer ùP2-OTBS with OTBS = tert-butyldiméthylsilyloxy and P2 as defined in claim 25.   32 - Method according to one of claims 27 to 31 characterized in that the coupling is carried out in the presence of a Lewis acid, under anhydrous conditions, preferably in the presence of TMSOTf or BF3.Et2O.   33 - Method according to one of claims 27 to 32 characterized in that the last deprotection is carried out by hydrogenolysis, preferably catalyzed by palladium on charcoal.