EP1675876A2 - Cyclodextrin amphiphilic derivatives, method for preparing same and uses thereof - Google Patents

Abstract

The invention concerns cyclodextrin derivatives of formula (I), wherein: R<1> = -NH-E-AA-(L<1>)p(L<2>)q; with E = C1-C4 hydrocarbon group, linear or branched, optionally with one or more heteroatoms; AA = residue of an amino acid; L<1> and L<2> = C6-C24 hydrocarbon group with optionally one or more heteroatoms; p and q = 0 or 1, one at least 0; R<2> = H, -CH3, isopropyl, hydroxypropyl, sulphobutylether; R<3> = H or R<2> except when R<2> = hydroxypropyl; all R<4>'s = -OH or R<2> except when R<2> = hydroxypropyl, or at least one of the R<4>'s = R<1>; n = 5, 6 or 7. The invention also concerns a method for preparing said derivatives, inclusion complexes and organized surfactant systems containing same.

Description

 AMPHIPHILIC DERIVATIVES OF CYCLODEXTRINS, THEIR PREPARATION PROCESS AND THEIR USES

DESCRIPTION TECHNICAL FIELD The present invention relates to new amphiphilic derivatives of cyclodextrins, more precisely of α-, β- and γ-cyclodextrins, as well as to their preparation process and to their uses. In addition to the fact that they exhibit properties of self-organization in an aqueous medium and of incorporation into organized surfactant systems, these amphiphilic derivatives show remarkable stability, which makes their manufacture, their conservation and their handling. particularly easy. They are likely to be used in all fields of application of cyclodextrins. However, their ability to be incorporated into organized systems can in particular be exploited in the pharmaceutical field to allow the transport, in particular by transmembrane route, in a living organism of active principles which are sparingly or not soluble in water, or to allow the selective delivery of drugs to target organs or cells to optimize their therapeutic action. It can also be used in the field of proteomics, for example to convey detergent molecules capable of destroying the layers lipids of cell membranes without altering membrane proteins.

STATE OF THE PRIOR ART Cyclodextrins are non-reducing cyclic oligosaccharides, which are obtained industrially by degrading amylose (that is to say the linear form of starch) by cyclodextrin glucosyltransferase, enzyme of origin bacterial. The three most frequently encountered cyclodextrins are the oc-, β- and γ-cyclodextrins which consist respectively of 6, 7 and 8 D-glucopyranosic units, linked together by glycosidic linkages α (l—> 4). The cyclodextrins have a three-dimensional structure in the form of a truncated cone, the wall of which is formed by D-glucopyranosic units, in chair conformation ⁴ Cι ^1,2 and .... delimits a cavity also called "cage". The secondary hydroxyl groups of the D-glucopyranosic units are located at the base of the wall of the truncated cone, while the primary hydroxyl groups of these units are located at the top of this wall. As a result, the outer part of the cyclodextrins is naturally hydrophilic while their inner part, which is lined with hydrogen atoms and interglucosidic oxygen atoms, is hydrophobic. This feature makes it possible to include in the cyclodextrin cage hydrophobic molecules to form inclusion complexes soluble in water. The biodegradable nature of cyclodextrins predisposes them to important applications in the pharmaceutical and food industries where the ability of cyclodextrins to serve as a "host" molecule makes it possible to protect fragile molecules, to ensure their controlled release or, in the case of hydrophobic molecules, their solubilization in an aqueous medium. Pharmaceutical specialties using cyclodextrins are already commercially available. Over the past fifteen years, a great deal of research has been carried out with the aim of increasing the amphiphilic nature of cyclodextrins, by grafting one or more hydrophobic groups, and thus making them capable of being inserted, by their hydrophobic part. , in lipid systems or to self-organize in an aqueous medium in the form of micelles, without however losing their capacity for complexing with respect to hydrophobic molecules. In particular, the research team to which the inventors belong has proposed, in FR-A-2 792 942 [1], amphiphilic derivatives of a-, β- or γ-cyclodextrin obtained by grafting a derivative steroid, via a spacer arm, on the carbon of the primary hydroxyl group of at least one D-glucopyranosic unit of these cyclodextrins. This team was able to obtain, from these derivatives, perfectly spherical micelles, comprising on average 24 monomers and lined on the surface by the cages of these monomers. It was also able to show, by different physicochemical techniques (diffusion of X-rays, differential calorimetry, R ³¹ P, ...) excellent incorporation of these derivatives in phospholipid matrices (Auzély-Velty et al., Carbohydrate Research, 1999, 318, 82-90 [2]). Now, continuing their work on cyclodextrins, the inventors have found that the grafting, still by means of a spacer arm, of an amino acid carrying one or two lipophilic groups, onto the primary hydroxyl group of at least one D-glucopyranosic unit of an α-, β- or γ-cyclodextrin, leads to the production of particularly advantageous amphiphilic derivatives insofar as they combine a very high affinity with respect to organized systems and a remarkable stability. It is this observation which is the basis of the invention.

SUMMARY OF THE INVENTION The subject of the invention is therefore amphiphilic derivatives of cyclodextrins which correspond to formula (I):

in which :

- R ¹ corresponds to formula (II): -NH-E-AA- (L ¹ ) _p (L ² ) _q (II) in which: • E represents a hydrocarbon group, linear or branched, saturated or unsaturated, comprising from 1 to 15 carbon atoms and optionally comprising one or more heteroatoms; • AA represents the remainder of an amino acid; L ¹ and L ² , identical or different, represent a hydrocarbon group, linear, branched and / or cyclic, saturated or unsaturated, comprising from 6 to 24 carbon atoms and optionally comprising one or more heteroatoms; • p and q, identical or different, are integers equal to 0 or 1, provided however that at least one of these integers is different from 0;

- R ² represents a hydrogen atom, a methyl group, an isopropyl group, a hydroxypropyl group or a sulfobutyl ether group; - R ³ represents a hydrogen atom or is identical to R ² except when R ² is a hydroxypropyl group;

- all R ⁴ represent either a hydroxyl group or R ² except when R ² is a hydroxypropyl group, or one or more R ⁴ are identical to R ¹ and the other R ^{4 (s)} represent either a group hydroxyl, ie R ² except when R ² is a hydroxypropyl group; - n is an integer equal to 5, 6 or 7. In what precedes and what follows, by "heteroatom" is meant an atom chosen from nitrogen, oxygen, sulfur and halogens (bromine, iodine , chlorine and fluorine). Furthermore, the term "residue of an amino acid" means the group of atoms which remains of this amino acid when the latter is covalently linked, on the one hand, to the spacer arm E and, on the other hand share in one and / or the other of groups L ¹ and L ² . According to a first preferred arrangement of the invention, in formula (II), E, which serves as a spacer arm, corresponds to formula (III): -CO-XG ¹ -, in which X represents an alkylene group forming a bridge and comprising from 1 to 8 carbon atoms, while G ¹ represents a group -CO-, -NH- or -NR- in which R is an alkyl group, advantageously Ci to Ce In formula (III), X represents, preferably, an alkylene group forming a bridge and comprising from 1 to 4 carbon atoms and, better still, 2 carbon atoms. The amino acid, the rest of which is symbolized by AA in formula (II), is preferably chosen from the twenty amino acids which conventionally enter into the constitution of proteins, namely aspartic acid, glutamic acid , alanine, arginine, asparagine, cysteine, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, tryptophan and valine. In particular, it is chosen from aspartic acid, glutamic acid, isoleucine, leucine and phenylalanine, aspartic acid and glutamic acid being particularly preferred. However, this amino acid can also be chosen from rarer amino acids such as, for example, β-alanine, γ-aminobutyric acid, α-aminoadipic acid, hydroxyproline, hydroxy-lysine, phenylserine, α, ε-diaminopimelic acid and ornithine, any amino acid being- a priori likely to be suitable since it comprises, by definition, two functional groups, one carboxylic acid, the other amino, allowing its covalent bond, on the one hand, to the spacer arm E, and, on the other hand, to at least one group L ¹ or L ² . The choice of amino acid depends in particular on the value which it is desired to give to p and q in formula (II), insofar as it must contain at least three functional groups so that p and q can be all two equal to 1 (that is, for the two groups L ¹ and L ^{2 to} be present), when it suffices - and it is even desirable to simplify the preparation of the cyclodextrin derivative - that it has only two functional groups when one of the integers p and q is equal to 0. According to the invention, it is preferred that AA is the remainder of an amino acid belonging to the series L. However, it is also possible that AA is the remainder of a D-series amino acid According to another preferred arrangement of the invention, in formula (II), L ¹ and / or L ² correspond to formula (IV): -G ² -Y in which G ² represents a group —C0-, -NH - or -NR- where R is an alkyl group, advantageously Ci to Ce, while Y represents a linear Cs to Cι ₈ alkyl chain or a cyclic or polycyclic group known to be lipophilic as a steroid group, for example derived from cholesterol, a polyaromatic group, for example derived from naphthalene, dansyl, anthracene or even a group derived from alkaloids. In formula (IV), Y preferably represents a C ₂ to C ₆ alkyl chain. Among the cyclodextrin derivatives according to the invention, those in which the spacer arm E is linked by an amide bond to the residue AA are preferred, this residue itself being linked by an amide bond to the group (s) L ¹ and / or L ² , for reasons of ease of preparation. In this case, E preferably corresponds to the formula: -CO-X-CO- in which X has the same meaning as above, while L ¹ and / or L ² preferably correspond to the formula: - NH-Y in which Y has the same meaning as before. In this case also, it is preferred that R ¹ corresponds to formula (VI):

in which :

- X and Y have the same meaning as above; while

- Z represents: • either a covalent bond, in which case R ⁵ represents a hydrogen atom, a methyl group, the side chain of an amino acid or a group of formula: - (CH ₂ ) t ^_ CO-NH- Y in which t is worth 1 or 2 and Y has the same meaning as above, • or a hydrocarbon group forming a bridge, comprising from 1 to 4 carbon atoms and comprising one or more heteroatoms chosen from 0 and N, in which case R ⁵ represents a primary amino group or a group of formula: -NH-CO-Y in which Y has the same meaning as above. In particular, when AA represents, in formula (II), the remainder of an amino acid chosen from aspartic acid, glutamic acid, isoleucine, leucine and phenylalanine, then, in formula (VI) ): - Z represents a covalent bond; - Y preferably represents a linear C ₈ to Cι ₈ and, better still, C ₁₂ to Cι ₆ alkyl chain; while

- R ⁵ represents a branched alkyl group with 4 carbon atoms, a benzyl group or a group of formula: - (CH ₂ ) _t -CO-NH-Y, in which t is equal to 1 or 2 and Y represents, preferably, a linear alkyl chain C ₈ Cι ₈ and more preferably C12 to Ciε. When AA represents, in formula (II), the remainder of an amino acid chosen from 1 'aci ^' of aspartic acid and glutamic acid, then, in formula (VI):

- Z represents a covalent bond;

- Y preferably represents a linear C ₈ to Cι ₈ and, better still, Cι ₂ to Ciε alkyl chain; while

- R ⁵ represents a group of formula: - (CH _{2) t} -CO-NH-Y, wherein t is 1 or 2 and Y is preferably a linear alkyl chain C ₈ Cι ₈ and, better still, in C ₁₂ to Cι ₆ . According to yet another preferred arrangement of the invention, the cyclodextrin derivatives contain only one substituent R ¹ per molecule of derivative. However, it is also possible that one or more or even all of the substituents R ⁴ are identical to R ¹ . The cyclodextrin derivatives according to the invention can be derivatives of a-, β- or γ-cyclodextrin. Preferably, the derivatives are used β-cyclodextrin, that is to say the derivatives of formula (I) in which n is equal to 6. According to the invention, these derivatives can in particular be: - dimethylated, in which case, in the formula ( I), R ² are methyl groups, R ³ are hydrogen atoms, while R ⁴ are methoxy groups when they are not identical to R ¹ , permethylated, in which case, in formula (I ), all R ² and R ³ are methyl groups, while R ⁴ represent methoxy groups when they are not identical to R ¹ ,

- 2-hydroxypropylated, in which case, in formula (I), all R ² are hydroxypropyl groups, R ³ are hydrogen atoms, while R ⁴ are hydroxyl groups when they are not identical to R ¹ ,

- sulfobutyl ethers, in which case, "in formula (I), the R ² , R ³ and R ⁴ are hydroxyl groups or sulfobutyl ether groups. Among the cyclodextrin derivatives according to the invention, very particularly preferred:

• JV ', "-didodecyl-JV _û ; - (6 ^I -amido-succinyl-6 ^I -deoxycyclomaltoheptaose) -L-aspartamide, • N', N" -didodecyl-N _α - (6 ^I - amido-succinyl-β ^I- deoxycyclomaltoheptaose) -L-glutamide,

• N ', N "-d ± dodecyl-N _a - (6 ^I -amido-succinyl-6 ^I -deoxy- 2 ^I -0-methyl-hexakis (2 ^{XI ~ VI1} , 6 ^{II-vι: ι:} - di-0-methyl) cyclo-maltoheptaose) -L-aspartamide, • N ', N "-didodecyl-N _α - (6 ^I -amido-succinyl-6 ^I -deoxy- 2 ^I -0-methyl-hexakis (2 ^{ττ → ττ} , 6 ^{II ~" VII} -di-0- methyl) cyclo-maltoheptaose) -L-glutamide,

• N ', N "-didodecyl-N _a - (6 ^I -amido-succinyl-6 ^I -deoxy- 2 ¹ , S ^ di-O-methyl-hexakis (2 ^II_VI1 , 3 ^II_VI1 , 6 ^{II ~ VII} - tri-0- methyl) cyclomaltoheptaose) -L-aspartamide, W ^|, -dodecyl- "-hexadecyl-W _ûr - (6 ^I -amidosuccinyl-6 ^I - deoxy-cyclomaltoheptaose) -L-aspartamide," N ", "-didodecyl-Nα- (6 ^I -amido-succinyl-6 ^I -deoxy- 2 ¹ , S ^ di-O-methyl-hexakis (2 ^{ττ ~ vιτ} , 3 ^{ll ~ VI1} , 6 ^II-VII -tri-0 - methyl) cyclomaltoheptaose) -L-glutamide,

• the W, i \? ^' "-dihexadecyl-N _û r- (6 ^I -amidosuccinyl-6 ^I -deoxy- 2 ¹ , S ^ di-O-methyl-hexakis (2 ^{II ~ VI1} , 3 ^II-VI1 , 6 ^{ι; [~ II} - tri-0- methyl) cyclomaltoheptaose) -L-aspartamide, and • N '-dodecyl-N _a - (6 ^I -amidosuccinyl-6 ^I -deoxy-2 ^I , 3 ^I -di- O-methyl-hexakis (2 ^{ΣI "VI1} , 3" - ^VI1 , β ^^^ - tri-O- methyl) cyclomaltoheptaose) -L-leucinamide. The cyclodextrin derivatives of formula (I) can be prepared by conventional coupling processes starting from monoamine derivatives corresponding cyclodextrins. In particular, they can be prepared by a process comprising the coupling of a monoamine derivative of an α-, β- or γ-cyclodextrin previously grafted from the spacer arm, with an amino acid previously grafted from the group or groups L ¹ and / or L ^2. Also, the subject of the invention is also a process for the preparation of cyclodextrin derivatives of formula (I) which comprises a step in which a cyclodextrin derivative of formula (VII) is reacted:

in which :

- E 'represents a hydrocarbon group, linear or branched, saturated or unsaturated, comprising from 1 to 15 carbon atoms, one or more heteroatoms and a free functional group capable of reacting with a hydroxyl, amino, carboxylic acid or thiol group d 'an amino acid to form a covalent bond;

- R ² represents a hydrogen atom, a methyl group, an isopropyl group, a hydroxypropyl group or a sulfobutyl ether group;

- R ³ represents a hydrogen atom or is identical to R ² except when R ² is a hydroxypropyl group;

- all R ⁴ represent either a hydroxyl group or R ² except when R ² is a hydroxypropyl group, or one or more R ⁴ represent a group -NH-E 'and the other R or R ⁴ represent either a hydroxyl group, ie R except when R ² is a hydroxypropyl group; - n is an integer equal to 5, 6 or 7;

with a compound of formula (VIII):

AA '- (L ¹ ) _p (L ² ) _q (VIII)

in which: * AA 'represents an amino acid comprising a hydroxyl, amino, carboxylic acid or free thiol group;

• L ¹ and L ² , identical or different, represent a hydrocarbon group, linear, branched and / or cyclic, saturated or unsaturated, comprising from 6 to 24 carbon atoms and optionally comprising one or more heteroatoms;

• p and q, identical or different, are integers equal to 0 or to 1, provided however that at least one of these integers is different from 0. The free functional group of E 'can in particular be a carboxylic acid group , a group derived from carboxylic acid (acid halide, acid anhydride), a primary or secondary amino group (-NHR where R is an alkyl group, advantageously in C1 to Cg), or a leaving group, according to the nature of the functional group of the amino acid with which it must react. In the foregoing and what follows, the term “leaving group” means a group capable of dissociating from the compound which carries it by attacking a nucleophilic center. Leaving groups are, for example, halogens, tosylates, mesylates and other sulfonates. For the preparation of the cyclodextrin derivative of formula (VII), the process according to the invention provides for reacting a monoamine derivative of cyclodextrin of formula (IX):

in which :

- R ² , R ³ and n have the same meaning as in formula (VII);

- all R ⁴ represent either a hydroxyl group or R ² except when R ² is a hydroxypropyl group, or one or more R ⁴ represent a group -NH ₂ and the other R or R ⁴ represent either a hydroxyl group , or R ² except when R ² is a hydroxypropyl group; with a group E 'precursor compound which comprises a free functional group capable of reacting with the amino group of the cyclodextrin derivative of formula (IX), this precursor compound becoming group E 'during the reaction. The precursor compound of group E ′ can in particular be a carboxylic acid group, a group derived from carboxylic acid or a leaving group. The monoamine cyclodextrin derivative of formula (IX) can itself be prepared by subjecting the monoazide derivative of cyclodextrin corresponding to a Staudinger reaction, using triphosphine and ammonia, as described in reference [1]. For the preparation of the compound of formula (VIII), the process according to the invention provides for the following stages: reacting an amino acid, the functional group of which is intended to react with the free functional group of group E 'of the cyclodextrin derivative of formula (VII) has been previously protected with a precursor compound of group L ¹ and / or a precursor compound of group L ² , this or these precursor compounds comprising a free functional group capable of reacting with a hydroxyl, amino or carboxylic acid group or thiol of an amino acid to form a covalent bond, and becoming the group (s) L ¹ and / or L ² during the reaction; then - deprotect the protected functional group of the amino acid. Of course, in the case where it is desired to graft only one of the two groups L ¹ and L ² on

1 amino acid and where the latter has more than two functional groups, then it is necessary to protect all groups which are not intended to react with the precursor compound of group L ¹ or L ² before carrying out this reaction. Furthermore, in the case where it is desired to graft on the amino acid two identical groups L ¹ and L ² , this grafting is carried out in a single step by reacting the amino acid with a precursor compound which is the same for the two groups, while, in the case where it is desired to graft on the amino acid two different groups L ¹ and L ² , this grafting is carried out in two successive stages: a first stage in which the acid is reacted amine with one of the precursor compounds of groups L ¹ and L ² after having protected the functional group of the amino acid intended to react with the other of these compounds, and a second step in which, after deprotection of said functional group, the amino acid is reacted with the other of said precursor compounds. Here too, the free functional group of the precursor compounds of groups L ¹ and L ² may in particular be a carboxylic acid group, a group derived from carboxylic acid, a primary or secondary amino group or a leaving group, depending on the nature of the functional group. of the amino acid with which it must react. When it is desired to prepare one of the preferred cyclodextrin derivatives according to the invention, that is to say a derivative of formula (I) in which R ¹ corresponds to formula (VI) above, then: the group E 'precursor compound is preferably an acid anhydride of formula (X):

in which X has the same meaning as above, which is reacted with the monoamine derivative of cyclodextrin of formula (IX) in an anhydrous medium, for example in anhydrous dimethylformamide, and under an inert atmosphere; - the amino acid, after protection of the amino group intended to react with the carboxylic acid group of the cyclodextrin derivative of formula (XI), for example by an N- (9-fluorenylmethoxycarbonyloxy) (Fmoc) group, is reacted with : • either a single precursor compound of formula: NH ₂ -Y in which has the same meaning as above, or two different precursor compounds of formula: NH ₂ -Y in which Y has the same meaning as above, the reaction then being carried out in two stages with intermediate protection and deprotection operations; • or a precursor compound of formula: NH ₂ -Y and a precursor compound of formula -COOH-Y, in which Y has the same meaning as previously, this reaction also being carried out in two stages with intermediate operations of protection and deprotection ; - the reaction between the cyclodextrin derivative (VII) and the compound of formula (VIII) is preferably carried out in the presence of peptide coupling agents such as N, JV'-diisopropylcarbodiimide (DIC) and hydroxybenzotriazole (HOBT) to avoid racemization. The amphiphilic cyclodextrin derivatives according to the invention have many advantages, including in particular that of having both a very high affinity with respect to organized surfactant systems and a remarkable stability, which makes them very easy to handle. Thus, these compounds are stable in the solid state for several months at room temperature and in the light. They are also stable for several weeks in aqueous or organic solution, which is not the case for lipid derivatives of the phospholipid type which are only stable at -80 ° C. They are in _. furthermore, relatively simple to prepare, essentially because their synthesis can be carried out by conventional peptide coupling methods. Their affinity for organized surfactant systems and, therefore, their ability to be incorporated into such systems can be exploited to allow the transport, in particular by transmembrane route, of hydrophobic compounds. Also, the invention also relates to inclusion complexes of cyclodextrin derivatives of formula (I) with hydrophobic compounds. These can be of different types: thus, they can in particular be principles drug active ingredients (steroids, neurotropes, antivirals, bacteriostats, vitamins, etc.), molecules useful in cosmetology, contrast agents for medical imaging, or compounds useful in proteomics such as, for example, detergents suitable for destroy the lipid layers of cell membranes without affecting the membrane proteins. These inclusion complexes can be prepared by conventional methods, for example by adding to a solution or a suspension of a cyclodextrin derivative of formula (I), a solution of the hydrophobic compound in a suitable organic solvent, for example the acetone. The invention also relates to organized surfactant systems comprising a cyclodextrin derivative of formula (I) or an inclusion complex of this derivative. The surfactants capable of forming such organized systems can be of different types. By way of example, mention may be made of phospholipids corresponding to the general formula below:

in which R ³ represents CH ₃ - (CH ₂ ) p-CO, p being an integer from 6 to 18. These phospholipids are capable of forming small unilamellar vesicles. This is the case, in particular, of dimyristoylphosphatidylcholine which corresponds to the above formula with p = 12. The invention will be better understood in the light of the additional description, which refers to exemplary embodiments of amphiphilic cyclodextrin derivatives according to the invention and which is given by way of illustration and not by way of limitation.

DETAILED PRESENTATION OF PARTICULAR EMBODIMENTS

Example 1: N ', N "-d ± d decγl-Ncg- (6 ^τ -aιιι ± ά -svLCC ± Ω.yl-6 ^τ - deoxy-cyclomalto eptaose) -L-aspartamide: The title compound is obtained, or compound 23, of formula:

23

by coupling 6 ^I -amidosuccinyl-6 ^I -deoxy-cyclomalto-heptaose, or compound 5, with N ', N "-didodecyl-L- aspartamide, or compound 21. 1.1. Preparation of compound 5: a) Preparation of tosylimidazone, or compound 1, of formula:

1 Tosyl chloride (80.27 g; 0.421 mol; 1 eq.) Dissolved in 250 mL of dichloromethane is added to imidazole in a 1 liter three-necked flask equipped with a thermometer and under an inert atmosphere. (65.08 g; 0.956 mol; 2.27 eq.) Dissolved in 250 mL of dichloromethane. The reaction medium is left stirred overnight at room temperature then filtered through celite and washed with 500 ml of an ethyl acetate / cyclohexane mixture (1/1). The filtrate is concentrated on a rotary evaporator and then the solid residue is taken up in 50 ml of ethyl acetate and precipitated in 500 ml of cyclohexane. The precipitate formed is filtered, dried and taken up in a minimum of dichloromethane. The organic phase is washed with water and then with a saturated solution of sodium chloride. The aqueous phase is extracted with dichloromethane. The organic phases are combined, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, the residual solid is recrystallized from isopropyl ether. After filtration and washing with ether, compound 1 is obtained with a yield of 75%. TLC: R _f = 0.6 eluent: CH ₂ Cl ₂ / MeOH 98/2 (v / v) Pf: 78 ° C

H NMR ^X CDC1 ₃ δ (ppm): 8 (s, 1H, H _3); 7.82 (d, 2H, H _b / _b ', ³ J _a -b = 8 Hz); 7.34 (d, 2H, H _c / o ', ³ Jb-a = 8 Hz); 7.28 (dd, 1H, ³ J = 1.6 Hz, ³ J = 1.4 Hz, H ₂ ); 7.08 (m, 1H, H ₃ ); 2.42 (s, 3H, H _e ) b) Preparation of 6 ¹ - (Op-tolylsulf onyl) -6 ¹ deoxy-cyclomaltoheptaose, or compound 2, of formula:

In a 500 L erlenmeyer flask, 25 g (0.022 mol; 1 eq.) Of β-cyclodextrin (Roquette Frères SA) are suspended in 200 ml of distilled water and then sodium hydroxide pellets (8.8 g) is added in a single fraction. The reaction medium becomes clear. Compound 1 (5 g; 0.022 mol; 1 eq.) Is rapidly added to the reaction medium (the tosylimidazole remains in suspension). After one hour, the pH is acidified to pH 6 with concentrated HCl. The white precipitate formed is filtered then washed with hot distilled water (2 x 100 ml) and with acetone (3 X 100 ml), then recrystallized from water. After filtration and washing with acetone, compound 2 is obtained with a yield of 21%.

TLC: R _f ≈ 0.4 eluent: NH ₄ 0H 6% / EtOH / BuOH 5/5/4 (v / v / v) Pf: 180 ° C (decomposition point between 175 ° C and 210 ° C)

¹ H NMR DMSO-d6 δ (ppm): 7.75 (d, 2H, H _b / _b ', ³ Ja-b = 9 Hz); 7.4 (d, 2H, H _{c /} c ', ³ Jb-a = 9 Hz); 5.8-5.5 (m, OH); 4.8 (m, 7H, Hi-CD); 4.5-4.3 (m, 2H, ; (m, 14H, H ₂ -CD / H ₄ -CD); 2.4 (s, 3H, CH ₃ )

ESI-MS +: m / z measured at 1290.2 for [M + H] ⁺ , calculated at 1290.2 for C ₄₉ H ₇₇ 0 ₃₇ S c) Preparation of 6 ^I -azido-6 ^I -deoxy-cyclo- malto-heptao ^' se, or compound 3, of formula:

In a 1 liter flask, compound 2 (6.74 g; 0.0052 mol; 1 eq.) Is suspended in 550 ml of water with stirring. An aqueous solution (12.5 mL; 0.052 mol; 10 eq.) Of 20% (m / v) lithium azide (Acros Organics) is added and the reaction medium is brought to reflux for 4 hours and then left at temperature. room for 4 days. After filtration of the insolubles, the solution is concentrated on a rotary evaporator until a volume of 10 mL. The oily residue is taken up in 190 ml of ethanol and then left in the refrigerator overnight. The mixture obtained is brought to a boil and filtered hot. The solid is washed with boiling ethanol then with acetone and dried under vacuum. After lyophilization, compound 3 is obtained with an estimated yield of 60%.

TLC: R _f = 0.3 eluent: NH ₄ OH 6% / EtOH / BuOH 5/5/4 (v / v / v) Mp: 160 ° C (decomposition)

NMR ^X HD ₂ 0 δ (ppm): 5.2-5.1 (m, 7H, Hi-CD); 4.1-3.8 (m, 30H, H ₃ -CD / H ₅ -CD / Hg-CD / H ₆ -CD); 3.75-3.55 (m, 14H, H ₂ -CD / H ₄ -CD)

ESI-MS +: m / z measured at 1166.5 for [M + Li] ⁺ , calculated at 1166.4 for C ₄₂ H ₆₉ N ₃ θ ₄ Li d) Preparation of 6 ^I -amino-6 ^I -deoxy- cyclo-maltoheptaose, or compound 4, of formula:

In a 2 liter flask, compound 3

(12.53 g; 0.0108 mol; 1 eq.) Is dissolved in 800 L of DMF. A solution of triphenylphosphine (11.38 g; 0.043 mol; 4 eq.) Dissolved in 40 ml of DMF is added slowly. After 3 hours with stirring at room temperature, the reaction medium is cooled to 0 ° C and 410 ml of 20% ammonia are added, the reaction medium is stirred overnight at room temperature then concentrated in a rotary evaporator. The oily residue is taken up in 600 ml of water, the white precipitate formed is filtered and washed with water (2 x 80 ml). The filtrate is then concentrated in vacuo and the solid residue is taken up in a minimum of water and then brought to pH 4.5 (initial pH of 8.9), the insolubles are filtered and the filtrate is passed through resin. ^® SP 1080 (Merck) in batch. Compound 4 is removed with 6% ammonia then the filtrate is concentrated on a rotary evaporator and taken up in a minimum of water. The insolubles are filtered and the filtrate is precipitated in acetone. After drying under vacuum overnight, 7.25 g of crude oil is dissolved again in water. The insolubles are filtered on filter paper and the filtrate is brought to pH 4.5. Half is then passed over a column of Lewatit SP 1080 resin and the other in batch. The various fractions are evaporated to dryness then taken up in a minimum of water and finally lyophilized. Compound 4 is obtained with an overall yield over the 2 stages of 45%.

TLC: R _f = 0.2 eluent: NH ₄ OH 6% / EtOH / BuOH: 5/5/4 (v / v / v)

Mp : 160 ° C (decomposition)

NMR ^X HD ₂ 0 δ (ppm): 5, 2-5, 05 (m, 7H, Hi-CD); 4, 1-3, 75 (m, 28H, H ₃ -CD / H5-CD / H ₆ ^{II ~ VII} -CD / H6 ' ^{: ι: I "VII} -CD); 3, 75-3, 5 (m , 14H, H ₂ -CD / H ₄ -CD); 3.25 (d, 1H, H ₆ ^I -CD, ³ J ₆ - ₅ = 10 Hz); 3.05 (d, 1H, Hg ^ CD, ³ Jg- ₅ = 10 Hz) ESI-MS +: m / z measured at 1134.5 [M + H] ⁺ , calculated at 1134.4 for C ₄₂ H ₂ N0 ₃₄ e) Preparation of 6 ^I -amidosuccinyl-6 ^I -deoxy-cyclomaltoheptaose, or compound 5, of formula:

In a clean and dry 100 ml flask, compound 4 (1 g; 0.88 mmol; 1 eq.) Is dissolved in 20 ml of anhydrous DMF under an inert atmosphere. The succinic anhydride (0.135 g; 1.34 mmol; 1.5 eq.) Dissolved in 6 ml of anhydrous DMF is added. The reaction medium is left under an inert atmosphere for 18 hours at room temperature. The reaction is stopped with 120 μL of water then the solution is precipitated in 200 ml of acetone. The solid obtained is filtered and then dried in a desiccator. The solid is taken up in a minimum of water, the insolubles are filtered and the filtrate lyophilized. Compound 5 is obtained with a yield of 55%.

TLC: R _f = 0.6 eluent: DMF / BuOH / H ₂ 0 1/2/1 (v / v / v) Pf: 160 ° C (decomposition)

NMR 4l pyridine-d5 δ (ppm): 8.75 (s, 1H, NH-CD); 7.9-7.6 (140H); 5.8-5.55 (m, 7H, Hi-CD); 4.95 to 3.95 (m, H ₃ -CD / H ₆ -CD / Hg '-CD / H ₅ -CD / H ₄ -CD / H ₂ -CD); 3 (m, 4H, H _b / H _c )

ESI-MS +: m / z measured at 1234.5 [M + H] ⁺ , calculated at 1234.4 for C ₄₆ H ₇₆ N0 ₃ -7

1.2. Preparation of compound 21: a) Preparation of N _a - (9-fluorenylmethoxycarbonyl) -L-aspartic acid, or compound 17, of formula:

17 In a dry 250 mL flask, 3.03 g (22.8 mmol; 1.2 eq.) Of L-aspartic acid (Fluka) are dissolved in 54 mL (68.8 mmol; 3.6 eq. ) an aqueous sodium carbonate solution at 13.5% (m / v). The medium is cooled in an ice bath to 0 ° C., then a solution of 6.41 g (19.0 mmol; 1 eq.) Of N- (9-fluorenylmethoxycarbonyloxy) succinimide (N-Fmoc) dissolved in 44 ml DMF is added with vigorous stirring (a precipitate forms in the reaction medium). Stirring is continued for 1 hour at room temperature. The mixture is then diluted in 665 ml of water, extracted with ether (1 X 80 ml) and then with ethyl acetate (2 x 60 ml). The resulting aqueous phase is cooled in an ice bath and acidified to pH 2 with hydrochloric acid concentrated (6 N). The aqueous phase containing the precipitated product (in the form of an oil) is extracted with ethyl acetate (6 x 60 mL). The organic phase resulting from the extraction is washed with a saturated aqueous solution of sodium chloride (3 x 35 mL), then with water (2 x 35 mL), dried over sodium sulfate and concentrated in an evaporator. rotary (35 ° C) until a small residual volume is obtained. Compound 17 is recrystallized by adding petroleum ether (approximately 10 times the residual volume) with vigorous stirring. After having allowed to settle for 2 hours at 4 ° C., the precipitate is filtered and then dried for 24 hours in a vacuum oven. 6.22 g (17.5 mmol) of compound 17 are isolated in the form of a fine white powder.

Crude formula: Cι ₉ Hι ₇ N0 ₆ , M = 355.35 g.mol ^-1 Yield: 92% Pf: 181 ° C TLC: R _f = 0.8 eluent: AcOH 60% / BuOH 4/6 (v / v)

ESI-MS +: m / z measured at 378.1 [M + Na] ⁺ , calculated at 378.1 for CιgHιNOgNa

Η NMR (dmso-dtr, 500.13 MHz) δ (ppm): 12.60 (si, 2H, COOH); 7.89 (d, 2H, H-4 / H-4 ', ³ J ₄ ~ ₃ = ³ J _4' - _{3 '} = 7.5 Hz); 7.72 (d, 1H, N ""); 7.70 (d, 2H, Hl / H-1 ', ³ Jι_ ₂ = ³ ûV- _2' = 7.5 Hz); 7.42 (t, 2H, H-3 / H-3 ', ³ J ₃ - ₂ = ³ J ₃ - ₄ = ³ J _3' - _{2 '} = ³ J _3' - ₄ '= 7.5 Hz) ; 7.33 (t, 2H, H-2 / H-2 ', ³ J ₂ _ι = ³ J ₂ - ₃ = ³ J _2' -i _' = ³ J _2' - _{3 '} = 7.5 Hz); 4.34 (m, 1H, H-α); 4.29 (d, 2H, H-8); 4.22 (t, 1H, H-7); 2.73 (dd, 1H, H-β, ³ J _β _ _α = 5.5 Hz, ³ J _β _β, = 16.4 Hz); 2.58 (dd, 1H, H-β ', ³ Jβ' - _α = 8.3 Hz, ³ J _β _p, = 16.4 Hz)

13 C NMR (dmso-ds, 125.77 MHz) δ (ppm) 172.8, 171, (CαH-COOH, C _β H ₂ -COOH); 155.9 (C-9); 143.9 (C-5 / C-5 '); 140.8 (C-6 / C-6 '); 127.7 (C-3 / C-3 '); 127.2 (C-2 / C- 2 '); 125.4 (Cl / C-1 '); 120.2 (C-4 / C-4 '); 65.8 (C-8); 50.6 (C-α); 46.7 (C-7); 36.1 (C-β) b) Preparation of N ', JV "-didodecyl-Ng- (9- fluorenylmethoxycarbonyl) -L-aspartamide, or compound 19, of formula:

19 In a 500 mL dry flask, 5.03 g

(14.2 mmol; 1 eq.) Of compound 17 are dissolved in 30 L of anhydrous DMF with stirring and under an inert atmosphere. 6.6 mL (42.5 mmol; 3 eq.) Of N, N'-diisopropylcarbodiimide (DIC) then 5.74 g (42.5 mmol; 3 eq.) Of hydroxybenzotriazole (HOBT), in solution in 20 mL of anhydrous DMF, are successively added. The reaction is maintained for 2 hours with stirring and under an inert atmosphere at room temperature. 7.91 g (42.7 mmol; 3 eq.) Of dodecylamine, dissolved in 100 mL anhydrous chloroform

(freshly distilled on P ₂ 0 ₅ ), are finally added to the reaction medium and the whole is left for

24 hours, with stirring and under an inert atmosphere, at room temperature (an abundant precipitate forms quickly). The mixture is then concentrated to

1 rotary evaporator (40 ° C) and taken up in DMF. The pasty solid is filtered and washed, first with DMF, then with ether. After drying overnight in a vacuum oven, 6.95 g (10.1 mmol) of compound 19 are isolated in the form of a fine white powder.

Crude formula: C43H6.7 3O4, M = 690.02 g.mol ^-1 Yield: 71% mp: 174 ° C

TLC: R _f = 0.9 eluent: CHCl ₃ / MeOH 9/1 (v / v) ¹ H NMR (CDCI ₃ , 500.13 MHz) δ (ppm): 7.78 (d, 2H, H-4 / H- 4 ', ³ J ₄ -a = ³ J ₄ ' - ₃ '= 7.5 Hz); 7.61 (d, 2H, Hl / H-1 ', ³ Jι- ₂ = ³ Ji'- ₂ ' = 7.5 Hz); 7.41 (tt, 2H, H-3 / H-3 ', ³ J ₃ - ₂ = ³ J ₃ -4 = ³ J ₃ ' -2 '= ³ J ₃ ' - ₄ '= 7.5 Hz) ; 7.32 (tt, 2H, H-2 / H-2 ',

³ J ₂ _ι = ³ J ₂ -3 = ³ J ₂ <-i '= ³ J ₂ ' -3 '= 7.5 Hz); 7.00 (tl, 1H,

N'f); 6.55 (d, 1H, N _α iî); 5.85 (tl, 1H, N'Η); 4.48 (ml, 1H, H-α); 4.42 (d, 2H, H-8, ³ J ₈ _ ₇ = 7.2 Hz); 4.23 (t, 1H, H-7, ³ J ₇ _ ₈ = 7.2 Hz); 3.23 (m, 4H, H-1α / H-1β); 2.87 (d, 1H, H-β, ³ Jβ_ _β <= 14.8 Hz); 2.52 (dd, 1H, H-β ',

³ Jβ'-α = 6.8 Hz, ³ Jβ_β, = 14.8 Hz); 1.49 (m, 4H, H-2α / H-

2β); 1.25-1.32 (m, H-3α to H-11α / H-3β to H-11β); 0.89

(t, 6H, H-12α / H-12β)

¹³ C NMR (CDCI ₃ , 125.77 MHz) δ (pp): 170.9, 170.3 (-CO- N'H, -CO-N "H); 156.1 (C-9); 143 , 6 (C-5 / C-5 '); 141.2 (C-6 / C-6 '); 127.6 (C-3 / C-3 '); 127.0 (C-2 / C-2 '); 125.0 (Cl / C-1 '); 119.9 (C-4 / C-4 '); 67.1 (C-8); 51.6 (C-α); 47.0 (C-7); 39.6 (C-lα / C-lβ); 37.9 (C-β); 31.8 (C-10α / C-10β); 29.1-29.6 (C-2α, C-4α to C-9α / C-2β, C-4β to C-9β); 26.8 (C-3α / C-3β); 22.6 (C-11α / C-11β); 14.0 (C-12α / C-12β) c) Preparation of N ', Àf-didodécyl-L-aspartamide, or compound. 21, of formula:

21 In a 100 mL flask, 2.09 g (3.03 mmol; 1 eq.) Of compound 19 are dissolved in 40 mL of a 20% (v / v) solution of piperidine in chloroform. The solution is heated for a few minutes at 40 ° C. The reaction medium, initially heterogeneous because of the low solubility of the starting product in chloroform, quickly becomes clear. The solution is then evaporated to dryness, under primary vacuum (40 ° C), to eliminate the maximum of piperidine (bp 101-106 ° C). The solid residue is taken up in 10 ml of chloroform to then be precipitated in 200 ml of hexane with stirring. After leaving decant for 2 hours at 4 ° C, the precipitate is filtered and then dried. A final stage of recrystallization from methanol (dissolution in a minimum of boiling methanol, filtration of the insoluble matter while hot and recrystallization at 4 ° C.) allows isolation by filtration, and after one night of drying in a vacuum oven, 1 , 20 g (257 mmol) of compound 21 in the form of a white powder.

Crude formula: C ₂₈ H ₅₇ N ₃ θ ₂ , M = 467.78 g.mol ^"1

Efficiency: 85%

Mp : 121 ° C

TLC: R _f = 0.4 eluent: CHCl ₃ / MeOH 9/1 (v / v)

[o] _D ²⁰ + 5 ° (c 0.27, CHC1 ₃ ) IR: 3311 cm ^-1 (wide) V (NH ₂ ); 1630 cm ^"1 V (C = 0 amides)

ESI-MS +: m / z measured at 468.5 [M + H] ⁺ , calculated at 468.5 for C ₂₈ H _5S N ₃ O ₂ ; m / z measured at 490.5 [M + Na] ⁺ , calculated at

490.4 for C ₂₈ H ₅₇ N ₃ θ ₂ Na.

NMR ^X IL (CDCI3, 500.13 MHz) δ (ppm): 7.51 (t, 1H, N 'H, ³ J _N Ή-ICX = 5.7 Hz); 6.26 (t, 1H, N "fl, ³ JιrΗ-ιβ = 5.5 Hz);

3.65 (dd, 1H, H-α, ³ J _α -β = 4.5 Hz, ³ J _α -β '= 7.1 Hz); 3.21 (m, 4H, H-lα / H-lβ); 2.61 (dd, 1H, H-β, ³ Jβ- _α = 4.5 Hz,

³ Jβ_ _β , = 14.4 Hz); 2.54 (dd, 1H, H-β ', ³ Jβ <- _α = 7.1 Hz,

³ Jβ'-β = 14.4 Hz); 1.48 (m, 4H, H-2α / H-2β); 1.25-1.32 (m, H-3α to H-11α / H-3β to H-11β); 0.88 (t, 6H, H-12GC / H-

12β)

¹³ C NMR (CDCI ₃ , 125.77 MHz) δ (ppm): 173.7 (-CO-N'H);

170.8 (-CO-N "H); 52.7 (C-α); 40.9 (C-β); 39.4, 39.2

(C-lα, C-lβ); 31.8 (C-10α / C-10β); 29.1-29.6 (C-2α, C-4α to C-9α / C-2β, C-4β to C-9β); 26.8 (C-3α / C-3β); 22, 6 (C-11α / C-11β); 14.0 (C-12α / C-12β)

1.3. Preparation of compound 23: In a dry 100 ml flask, 407.7 mg (0.33 mmol; 1 eq.) Of compound 5, previously lyophilized, are dissolved in 10 ml of anhydrous DMF with stirring and under an inert atmosphere. 205 μL (1.32 mmol; 4 eq.) Of DIC then 179.3 mg (1.33 mmol; 4 eq.) Of HOBT, in solution in 5 ml of anhydrous DMF, are successively added. The reaction is maintained for 2 hours with stirring and under an inert atmosphere at room temperature. 185.3 mg (0.40 mmol; 1.2 eq.) Of compound 21, dissolved in 15 ml of anhydrous chloroform (freshly distilled over P2O5), are added to the reaction medium. After 24 hours of stirring at room temperature and under an inert atmosphere, the reaction is. stopped by adding 100 μL of water. The solution is concentrated on a rotary evaporator (40 ° C) until an oily residue is obtained, which is then precipitated in 100 ml of acetone with stirring. The precipitate is recovered by centrifugation (10,000 rpm;

15 min), washed with clean acetone and dried overnight in a hood. 486.8 mg of crude product are thus isolated and are purified by HPLC with normal phase polarity

(μPorasil ^® ; A / B 20/80 (v / v) with A: CH3OH and

B: CHCI3 / CH3OH / NH3 20% (80 / 19.5 / 0.5) (v / v / v) in

20 min). 465.9 mg (0.28 mmol) of compound 23 are isolated in the form of a fine white powder after lyophilization. Crude formula: C7 ₄ H ₁ 30N4O38, M = 1683.85 g. mol ^-1 Yield: 85%

Mp: 160 ° C (dec.) TLC: R _f = 0.2 eluent: CHCl ₃ / MeOH / H ₂ 0 6/3 / 0.5 (v / v / v) [α] _D ²⁰ + 83 ° ( c 0.26, DMF)

ESI-HRMS (high resolution with detection in positive mode): m / z measured at 1683.8441 [M + H] ⁺ , calculated at 1683, 8441 for C ₇₄ Hi ₃ iN ₄ θ ₃₈ (deviation: 0 ppm); m / z measured at 1705.8169 [M + Na] ⁺ , calculated at 1705.8261 for C ₇₄ Hi ₃ cιN ₄ 0 ₃₈ Na (deviation: 5.4 ppm)

¹ H NMR (pyridine-ds, 500.13 MHz) δ (ppm): 9.14 (d, 1H, NαH); 8.80 (t, 1H, NHCD); 8.68 (t, 1H, N "H); 8.51 (t, 1H, WH); 5.38 (m, 1H, H-α); 5.42-5.61 (m, 6H, H -1 ^{II_ VII} _C D); 5.43 (d, 1H, Hl ¹ ^); 4.62-4.75 (m, H-3 ^II-VII _C D), 4.62 (H ^ _CD ) 4 , from 55 to 4.64 (m, 6H ^VII _CD ^I3); 4.31 to 4.52 (m, _{5 H} _ ^II - II _CD ^V _{/ H} _ ₆ II I ^{I V} _{CD) 4} ^. ₄₂ (H-Ô ^ D); 4.15-4.29 (m,

H-4 ^II_VII CD); 4.19 (H- ^β 'cD); 4.06 (H-β ^ co); 3.99-4.14 (m, H-2 ^{II "VII} _CD ); 3.91 (dd, 1H, H-2 ^I _CD ); 3.81 (t, 1H, H-4 ^I _CD ); 3 , 36, 3.31 (2m, 4H, H-lα, H-lβ); 3.12 (d, 1H, H-β); 3.07 (d, 1H, H-β '); 2.5 -3.0 (m, 4H, Hb / Hc); 1.53, 1.46 (2m, 4H, H-2α, H-2β); 1.20, 1.18 (H-30C, H-3β ); 1.13 (H-llα / H-llβ); 1.05-1.25 (m,

H-4α to H-10α / H-4β to H-10β); 0.75 (t, 6H, H-12α / H-12β) ¹³ C NMR (pyridine-ds, 125.77 MHz) δ (ppm): 173.6 (Ca); 173.4 (Cd); 172.3 (-CO-N'H); 171.5 (-CO-

N "H-); 104.1-104.6 (C-1 ^I_VII _C D); 85.8 (C-4 ^I _CD ); 83.7-

84.3 (C-4 ^II_VII _C D); 74.1-75.4 (C-3 ^I ~ ^VII CD / C-5 ^{II "VII} CD / C-2 ^1-

^VII CD); 72.3 (CS ¹ ^); 62.6 (C- ^β1 ^); 61.9-62.3 (C-6 ^{II_ VII} _CD ); 52.0 (C-α); 40.3, 40.5 (C-1α, C-1β); 39.1 (C-β); 32.6 (C-10α / C-10β); 32.1, 32.4 (Cb, Cc); 30.5 (C-2α / C-2β); 30.1 (C-4α / C-4β); 30.1 to 30.6

(C-5α to C-9α / C-5β to C-9β); 27.8, 27.9 (C-3α, C-3β); 23.4 (C-11α / C-11β); 14.8 (C-12α / C-12β)

Example 2: Preparation of N ^ -W'-didodecyl-N _α - ^ - amidosuccinyl-6 ^I- deoxy-cyclomalto eptaose) -L-glutamide: The title compound, or compound 24, of formula:

by coupling the compound 5 synthesized in example 1 above, with the N ′,. N "-didodecyl-L-glutamide, or compound 22.

2.1. Preparation of compound 22: a) Preparation of N _a - (9-fluorenylmethoxycarbonyl) -L-glutamic acid, or compound 18, of formula:

18 Compound 18 is prepared by following the same experimental protocol as that described for the preparation of compound 17 in Example 1 above, but using: - 3.40 g (23.1 mmol; 1.2 eq. ) L-glutamic acid (Fluka) - 54.5 mL (69.3 mmol; 3.6 eq.) 13.5% (m / v) aqueous sodium carbonate solution, and - 6.50 g (19.3 mmol; 1 eq.) of N- (fluorenylmethoxycarbonyloxy) succinimide. 6.07 g (16.4 mmol) of compound 18 are thus obtained.

Crude formula: C ₂ oHι ₉ N0 ₆ , M = 369.37 g.mol ^-1 Yield: 85%

Mp : 197 ° C

TLC: R _f = 0.9 eluent: AcOH 60% / BuOH 4/6 (v / v) ESI-MS +: m / z measured at 392.2 [M + Na] ⁺ , calculated at 392.1 for C ₂ oHι N0 ₆ Na; m / z measured at 408.2 [M + K] ⁺ , calculated at 408.1 for C ₂₀ HιsNO ₆ K

^X H NMR (DMSO-d _6, 500.13 MHz) δ (ppm) 12.42 (bs, 2H, COOiî); 7.89 (d, 2H, H-4 / H-4 ', ³ J ₄ _ ₃ = ³ J ₄ <- ₃ ' = 7.5 Hz); 7.72 (d, 2H, Hl / H-1 ', ³ Jι-- ₂ = ³ Jι-- ₂ ' = 7.5 Hz); 7.67 (d, 1H, N _α H, ³ J _NC .HH = 8.2 Hz); 7.42 (t, 2H, H-3 / H-3 ', ³ J ₃ - ₂ = ³ J ₃ -4 = ³ J ₃ ' -2 '= ³ J ₃ ' -4- = 7.5 Hz) ; 7.33 (t, 2H, H-2 / H- 2 ', ³ J ₂ _ι = ³ J ₂ - ₃ = ³ J ₂ ' -ι- = ³ J ₂ '-3' = 7.5 Hz); 4.28 (d, 2H, H-8); 4.23 (t, 1H, H-7); 4.00 (ddd, 1H, H-α, ³ J _α -β = 5.0 Hz, ³ J _α _β, ≈ 1.6 Hz, ³ Jα-N _H = 8.2 Hz); 2.32 (m, 1H, Hγ); 1.99 (m, 1H, H-β); 1.79 (m, 1H, H-β ') b) Preparation of N', N "-d ± dodecyl-Ng- (9-fluorenyl-methoxycarbonyl) -L-glutamide, or compound 20, of formula:

Compound 20 is prepared by following the same experimental protocol as that described for the preparation of compound 19 in Example 1 above, but using: - 5.89 g (16.0 mmol; 1 eq.) Of compound 18 - 7.4 mL (47.8 mmol; 3 eq.) of DIC - 6.47 g (47.9 mmol; 3 eq.) Of HOBT - 8.87 g (47.9 mmol; 3 eq.) Of dodecylamine. 9.29 g (13.2 mmol) of compound 20 are thus obtained.

Crude formula: C ₄₄ H ₆₉ N ₃ θ ₄ , M = 704.05 g. soft ^"1

Efficiency: 83%

Mp : 165 ° C

TLC: R _f = 0.9 eluent: CHCl ₃ / MeOH 9/1 (v / v) ¹ H NMR (CDC1 ₃ , 500.13 MHz) δ (ppm): 7.77 (d, 2H, H-4 / H- 4 ', ³ J ₄ -3 = ³ J ₄ ' -3 '= 7.5 Hz); 7.61 (d, 2H, Hl / H-1 ', ³ Jι_ ₂ = ³ Ji'- ₂ ' = 7.5 Hz); 7.41 (t, 2H, H-3 / H-3 ', ³ J ₃ - ₂ = ³ J ₃ -4 = ³ J ₃ , _ ₂ , = ³ J ₃ -_ ₄ , = 7.5 Hz) ; 7.32 (t, 2H, H-2 / H-2 ', ³ J ₂ -ι = ³ J ₂ - ₃ = ³ J ₂ ' -ι- = ³ J ₂ '-3' = 7.5 Hz) ; 6.69 (bt, 1H, N'H); 6.24 (dl, 1H, NαH, ³ J _NαH -H = 6.8 Hz); 5.81 (tl, 1H, N "H); 4.37 (d, 2H, H-8, ³ J ₈ - ₇ = 7.2 Hz); 4.22 (t, 1H, H-7, ³ J ₇ - ₈ = 7.2 Hz); 4.17 (m, 1H, H-α); 3.26 (q, 4H, H-lα / H-lγ); 2.40 (m, 1H, H -γ); .2.31 (m, 1H, H-γ '); .2.11 (m, 1H, H-β); 2.00 (m, 1H, H-β'); 1.51 (m, 4H, H-2α / H-2γ); 1.23-1.33 (m, H-3α to H-llα / H- 3γ to H-llγ); 0.89 (t, 6H, H -12α / H-12γ)

c) Preparation of N ", A-didodecyl-L-glutamide, or compound 22, of formula:

22 Compound 22 is prepared by following the same operating protocol as that described for the preparation of compound 21 in Example 1 above, but using 9.29 g (13.2 mmol; 1 eq.) Of compound 20 5.01 g (10.4 mmol) of compound 22 are thus obtained.

Crude formula: C ₂₉ H ₅₉ N ₃ 0 ₂ , M = 481.81 g. ol ^-1 Yield: 79%

Mp : 118 ° C

TLC: R _f = 0.4 eluent: CHCl ₃ / MeOH 9/1 (v / v)

[α] _D ²⁰ + 45 ° (c 0.25, CHC1 ₃ )

IR: 3324 cm ^-1 V (NH ₂ ); 1633 cm ^-1 V (C = 0 amides) ESI-MS +: m / z measured at 504.6 [M + Na] ⁺ , calculated at 504.5 for C ₂₉ H ₅₉ N ₃ 0 ₂ Na

NMR * Η (CDC1 ₃ , 500.13 MHz) δ (ppm): 7.37 (tl, 1H,

N'iï); 6.27 (tl, 1H, N "H); 3.40 (t, 1H, H-α, ³ J _α " _β = 6.8

Hz); 3.21 (m, 4H, H-lα / H-lγ); 2.30 (m, 2H, H-γ); 1.93 (m, 2H, H-β); 1.48 (m, 4H, H-2α / H-2γ); 1.22-1.33 (m, H-3α to H-llα / H-3γ to H-llγ); 0.87 (t, 6H, H-12α / H-12γ, Jιια "i2α = Jιιγ" i2γ = 7.0 Hz)

¹³ C NMR (CDCI3, 125.77 MHz) δ (ppm): 174.6 (-CO-N'H);

172.5 (-CO-N "H); 54.1 (C-α); 39.5, 38.9 (C-lα, C-lγ); 33.1 (C-γ); 31.8 (C-10α / C-10γ), - 31.6 (C-β);

29.1-29.6 (C-2α, C-4α to C-9α / C-2β, C-4γ to C-9γ); 26.8 (C-3α / C-3γ); 22.5 (C-llα / C-llγ); 14.0 (C-12α / C-12γ)

2.2. Preparation of compound 24: The coupling of compounds 5 and 22 is carried out by following the same operating protocol as that described for the preparation of compound 23 in Example 1 above, but using: - 1.04 g (0, 84 mmol; 1 eq.) Of compound 5 - 525 μL (3.39 mmol; 4 eq.) Of DIC - 456.5 mg (3.38 mmol; 4 eq.) Of HOBT - 610.2 mg (1, 27 mmol; 1.5 eq.) Of compound 22. This gives 1.10 g (0.65 mmol) of compound 24.

Crude formula: C75H132N4O38, M = 1697.88 g. soft ^"1

Yield: 77%

Mp : 160 ° C (dec.)

TLC: R _f = 0.2 eluent: CHCl ₃ / MeOH / H ₂ 0 6/3 / 0.5 (v / v / v)) [] _D ²⁰ + 69 ° (c 0.27, DMF)

ES-HRMS (high resolution with detection in positive mode): m / z measured at 1697.8624 [M + H] ⁺ , calculated at 1697.8598 for C ₅ H ₁ 33N ₄ O38 (deviation: 1.6 ppm) NMR R (pyridine-ds, 500.13 MHz) δ (ppm): 9.17 (d, 1H, N _α iï); 8.82 (t, 1H, NH _CD ); 8.56 (t, 1H, N "tf); 8.37 (t, 1H, N'H); 4.94 (m, 1H, H-α); 5.56-5.60 (m), 5.55

(d), 5.46 (d) (6H, H-1 ^II_VII CD); 5.43 (d, 1H, H-1 ^X _C D)}

4.62-4.76 (m, ; 4.56-4.64 (m,

_H _ ₆ II- ^V H _CD) . 4.28-4.53 (m, ^II-VII _C D); 4.41 (H-5 ^J CD); 4.14-4.27 (m, H-4 ^II-VII _CD ); 4.19 (H-β ^); 4.06 (H-6 ^,]: _C D); 3.98-4.13 (m, H-2 ^{II "V1I} _CD ); 3.92 (dd, 1H, H-2 ^Σ CD); 3.80 (t, 1H, H-4 ^I CD); 3 , 35, 3.30 (m, 4H, H-lα, H-lγ); 2.6-3.0 (m, Hb / Hc); 2.61 (m, H-γ / H-γ ') ; 2.61 (m, H-β); 2.34 (m, 1H, H-β '); 1.50, 1.47 (m, 4H, H-2α, H-2γ); 1.18 (H-3α / H-3γ); 1.05-1.25 (m,

H-4α to H-llα / H-4γ to H-llγ); 0.75 (t, 6H, H-12α / H-12γ) ¹³ C NMR (pyridine-d ₅ , 125.77 MHz) δ (ppm): 173.7 (Ca); 173.6 (Cd); 173.2 (-CO-N'H); 172.9 (-CO- N "H); 104.1-104.6 (C-1 ^I_VII _C D); 85.8 (C-4 ^I _CD ); 83.8- 84.2 (C-4 ^{II "VII} _CD ), * 74.1-75.4 (C-3 ^{I" VII} _CD / C-5 ^{II "V:!: I} _C D / C-2 ^{: I:" VII} _CD ); 72.3 (C-Ô ^ D); 62.7 (C-6 ^X _CD ); 62.0-62.3 (C-6 ^{II_ VII} _CD ); 41.6 (C-α); 40.3 (C- lα / C-lγ); 33.8 (C-γ); 32.6 (C-10α / C-10γ); 32.1, 32.3 (Cb, Cc); 30.5 (C-2α / C-2γ); 30.1 (C-4α / C-4γ); 30.1-30.7 (C-5α to C-9α / C-5γ to C-9γ); 30.0 (C-β ); 27.8, 27.9 (C-3α, C-3γ); 23.4 (C-llα / C-llγ); 14.8 (C-12α / C-12γ)

Example 3: Preparation of N ', W'-didodecyl-WOr (6 ^I -amidosuccinyl-6 ^I -deoxy-2 ^I -0-met yl- exakis (2 II-VII, 6-II-VII -di- O- methyl) cyclomaltoheptaose) -L-aspartamide: The title compound, or compound 25, of formula:

25 by coupling the 6 ^I -amidosuccinyl-6 ^I -deoxy-per (2,6-di-O-methyl) cyclomaltoheptaose, or compound 9, with the compound 21 synthesized in Example 1 above.

3.1. Preparation of compound 9 a) Preparation of 6 ^I -azido-6 ^I -deoxy-2 ^I -0- methyl-hexakis {2 ^{ll "vττ} , 6 ^{ι: E" v]: ι} -di-0-methyl) cyclomalto- heptaose, or compound 7, of formula:

In a dry 250 mL bicol, 4.45 g (3.84 mmol; 1 eq.) Of compound 3 synthesized in Example 1 above, previously dried in a vacuum oven, are dissolved in 55.7 ml of anhydrous DMF with stirring and under an inert atmosphere. After placing the reaction medium in a bath at 8 ° C., 55.7 ml of anhydrous DMSO are introduced, then 8.25 g (53.8 mmol; 14 eq.) Of barium oxide and 8.50 g ( 26.9 mmol; 7 eq.) Of barium hydroxide octahydrate are successively added. Finally, 6 ml (63.0 mmol) of methyl sulfate are added, and the whole is maintained for 72 hours at 8 ° C., with stirring and under an inert atmosphere. 27.5 ml of ammonia (20% v / v solution) are then added slowly to the greyish suspension obtained. The mixture is then kept stirring for 3 hours and at room temperature. After allowing the suspension to settle for 2 hours at 4 ° C, the supernatant is isolated in a 500 ml flask, concentrated in a rotary evaporator (50 ° C) until an oily residue is obtained, then taken up in 300 ml of dichloromethane. The residual solid from the decantation is taken up with dichloromethane (3 X 100 mL) and then filtered. The organic phases are combined, washed with a saturated aqueous sodium chloride solution (3 X 130 mL), then with water (3 x 130 mL), dried over sodium sulfate and concentrated in a rotary evaporator (40 ° C) until a residual oil is obtained. This residue is precipitated in 250 ml of hexane with stirring. The precipitate is filtered, washed with hexane and dried in a vacuum oven. 3.59 g (2.67 mmol) of a fine white powder, corresponding to compound 7, and per (2,6-di-0-methyl) cyclomaltoheptaose (DIMEB), formed from the β-CD regenerated during the synthesis of compound 3. This mixture will be purified during the next step (preparation of compound 8).

Crude formula: C ₅ 5H ₉ 5N ₃ θ34, - = 1342.36 g.mol ^"1

Yield: 70%

TLC: R _f = 0.9 eluent: CHCl ₃ / MeOH 9/1 (v / v)

Mp : 160 ° C (dec.)

IR: 2101 cm ^"1 V (N ₃ ) ESI-MS +: m / z measured at 1364.5 [M + Na] ⁺ , calculated at 1364.6 for C ₅₅ Hg ₅ N ₃ 0 ₃₄ a

H NMR (CDC1 _3, 500.13 MHz) δ (ppm) 5.25 to 5.32 (H-1 _CD); 3.99-4.05 (H-3 _CD ); 3.88-3.98 (H-5 _CD ); 3.70-3.85 (H-6 _C D / H-6'CD); 3.60 (OCH ₃ -6 _CΏ ); 3.53-3.68 (H-4 _CD ); 3.43 (OCH ₃ -2 _CΌ ); 3.40-3.46 (H-2 _CD ) b) Preparation of 6 ^I -amino-6 ^I -deoxy-2 ^I -Q- heptaose, or compound 8, of formula:

8 In a 500 mL flask, 3.51 g (2.61 mmol; 1 eq.) Of compound 7 are dissolved in 200 L of DMF with stirring. A solution of 2.74 g (10.46 mmol; 4 eq.) Of triphenylphosphine (freshly recrystallized from boiling ethanol) dissolved in 10 ml of DMF is added. After 2 hours with stirring at room temperature, the reaction medium is cooled to 0 ° C. in an ice bath and 99 ml of ammonia (20% v / v solution) are slowly added. The reaction is maintained for 18 hours with stirring at room temperature. The solution is then concentrated on a rotary evaporator (40 ° C) and the oily residue is taken up in 150 ml of water. The white precipitate formed (mixture of triphenylphosphine and triphenylphosphine oxide) is filtered and washed (2 x 20 mL of water). The filtrate is concentrated under vacuum at 40 ° C, then taken up in a minimum of water and adjusted to pH = 4.5 by adding a few drops of 1N HCl. This solution is passed through a column of resin exchanger of ions (V = 160 cm ³ ), filled with Lewatit SP 1080 anionic resin, previously regenerated by three successive washing cycles alternating 10% ammonia, water, and 0.1 M HC1. Compound 8 is strongly retained on the column, while that the DIMEB present is eluted with water (5 column volumes). Compound 8 is in turn eluted with a 10% ammonia solution (3 column volumes). The basic eluate is evaporated to dryness on a rotary evaporator (40 ° C); the residue is taken up in a minimum of water and then lyophilized. 1.68 g (1.28 mmol) of compound 8 are thus isolated, in the form of a white powder.

Crude formula: Cs ₅ H ₉₇ 0 ₃₄ , M = 1316.36 g.mol -1 Estimated yield: 75% Pf: 160 ° C (dec.)

TLC: R _f = 0.4 eluent: CHCl ₃ / MeOH 9/1 (v / v) IR: absence of V band (N3)

ESI-MS +: m / z measured at 1316.8 [M + H] ⁺ , calculated at

1316.6 for C ₅₅ H ₉ 1 ₃ NO ₃ 4

NMR ^ Η (D ₂ 0, 500.13 MHz) δ (ppm) 5.24-5.30 (7H, Hl ^1-

VII -II-VII CD); 3.92-3.98 (H-3; 3.80-3.90 (H-5 ¹ ~ ^{V ^} _CD ), I-VII 3.72-3.80 (H-6 ^{I: "VII} CD, H- 6, I; 3.71 (H-5 ^X CD); 3.61 (0C # ₃ -6CD) ' ^* 3.58-3.65 (H-4 ^{I]: "VII} CCDD) /; 3 , 55 ((HH - 44 ^II _CCDD ));; 3.43 (OCH ₃ -2 _CD ); 3.38-3.44 (H-2 I-VII _CD ); 3.06 (dd, 1H,

H-6 ^X c _D ); 2.92 (dd, 1H, H-6 ' ^X CD)

13 C NMR (D ₂ 0, 125.77 MHz) δ (ppm) 99.3-99.9 (C-1 I-VII CD il, 5-82, 2 (C-4 I-VII -VII CD / C-2 I CD / 72,4-72,7 (C-3 I-VII CDJ

70.4 to 72.7 ; 59.6-59.8 (0CH ₃ -6 _C D) 58.8-59.0 (OCH ₃ -2 _C D); 41.5 (C- ^β1 ^) c) Preparation of 6 ^I -amidosuccinyl-6 ^I -deoxy-

2 ^I -Q-methyl-hexakis (2 ^X I ^I I ^" - ^V V ^I I ¹ I, 6 (-II-VII di-O-methyl) cyclomaltoheptaose, or compound 9, of formula

In a 100 ml flask, 1.093 g (0.83 mmol; 1.1 eq.) Of compound 8, previously lyophilized, are dissolved in 20 ml of anhydrous DMF with stirring and under an inert atmosphere. 75.7 mg (0.76 mmol; 1 eq.) Of succinic anhydride dissolved in 5 ml of anhydrous DMF are then added. The the reaction medium is maintained, with stirring and under an inert atmosphere, for 18 hours at room temperature. The reaction is stopped by adding 100 μL of water. The solvent is evaporated to dryness under vacuum (40 ° C) then the residue is taken up in a minimum of water until complete dissolution. This acid solution is passed over a column of ion exchange resin (V = 10 cm ³ ), filled with anionic resin Lewatit SP 1080, previously regenerated by three successive washing cycles alternating 10% ammonia, water, and HCl 0.1 M. Compound 9 is eluted with water while compound 8 in excess (in the form of an ammonium ion) is strongly retained in the column. The eluate is concentrated in a rotary evaporator (40 ° C) and then lyophilized. 821 mg (0.58 mmol) of compound 9 are obtained in the form of a white powder.

Crude formula: C59H101NO37, M = 1416.44 g.mol ^-1 Yield: 77% mp: 160 ° C (dec.)

TLC: R _f = 0.2, eluent: CHCl ₃ / MeOH 9/1 (v / v)

ESI-MS -: m / z measured at 1414.5 for [MH] ^~ , calculated at

1414, 6 for C59H100NO37 3.2. Preparation of compound 25: In a dry 50 ml flask, 338.9 mg (0.24 mmol; 1 eq.) Of compound 9, previously lyophilized, are dissolved in 10 ml of anhydrous DMF with stirring and under an inert atmosphere. 149 μL (0.96 mmol; 4 eq.) Of DIC then 129.3 mg (0.96 mmol; 4 eq.) Of HOBT, in solution in 5 ml of anhydrous DMF, are successively added. The reaction is then maintained for 2 hours with stirring and under an inert atmosphere at room temperature. 169.6 mg (0.36 mmol; 1.5 eq.) Of compound 21, dissolved in 15 ml of anhydrous chloroform (freshly distilled over P2O5), are finally added to the reaction medium. After 24 hours of stirring at room temperature and under an inert atmosphere, the reaction is stopped by adding 100 μL of water. The solution is evaporated to dryness under primary vacuum (40 ° C), the residue is taken up in 20 ml of chloroform and the insolubles are filtered. The filtrate is concentrated on a rotary evaporator (30 ° C) and purified using a chromatographic column on silica gel 60 Fluka (elution with CHC1 ₃ / CH ₃ 0H 98/2 then 95/5 (v / v)). 267.0 mg (0.14 mmol) of compound 25 are thus isolated in the form of a white powder after lyophilization.

Crude formula: C ₈ 7Hι ₅ gN4θ ₃ 8, M = 1866.20 g.mol ^-1 Yield: 60%

Mp : 160 ° C (dec.)

TLC: R _f = 0.3 eluent: CHCl ₃ / MeOH 8/2 (v / v)

[α] _D ²⁰ + 84 ° (c 0.25, CHC1 ₃ )

IR: 3300-3500 cm ^-1 (wide) v (OH); 1655 cm ^-1 v (C≈O amides)

ES-HRMS (high resolution with detection in positive mode): m / z measured at 1866, 0394 [M + H] ⁺ , calculated at 1866, 0476 for C87Hι ₅ 7 θ ₃₈ (deviation: 4.4 ppm); m / z measured at 1888, 0214 [M + Na] ⁺ , calculated at 1888, 0295 for C ₈₇ Hi ₅ N ₄ θ ₃₈ Na (deviation: 4.3 ppm) ^X NMR (CDCl3, 500.13 MHz) δ (ppm): 7.50 (7.58 *) (t, 1H, N N'H or "fl); 7.44 (7.38 *) (d , 1H, N "χf0; 6.27 (6.21 *) (t, 1H, N'H or N"H); 6.11 (t, 1H, NH _CD ); 4.93-5.10 ( m, ; 4.64 (m, 1H, H-α); 3.88- 3.96 (m, HS ^{1 "11} - ^) 3.63 (m, OCH ₃ -6 _CD ); 3.55-3.77 (m, ; 3.40 (m, 0Ci? ₃ -2 _C D); 3.38-3.50 (m, H-4 ^{I "VII} _CD ); 3.22-3.32 (m, H-2 ^{I" VII} _CD ); 3.19 (m, H-lα / H-lβ); 2.88 (dd, 1H, H-β); 2.4-2.7 (m, 4H, Hb / Hc); 2.42 (dd, 1H, H-β '); 1.47 (m, H-2α / H-2β); 1.24-1.31 (m, H-3α to H-11α / H-3β to H-11β); 0.87 (t, 6H, H-12α / H-12β) * conformers

¹³ C NMR (CDCI ₃ , 125.77 MHz) δ (ppm): 171.9, 171.8,

171.2, 170.2 (4s, -CO-NH); 100.8-101.5 (Cl ¹ ^ ¹³ ^); 83.0-83.7, 84.9 (C-4 ^{I "VII} _C D); 81.7-82.3 (C-2 ^{X" VI: E} CD);

73.0-73.3 (C-3 ^I_VII CD); 69.6-71.6 (C-5 ^{I_ II} _C D); 70.6-71.0 (C-6 ^I_VII CD); 60.2-60.5 (OCH ₃ -6 _C D); 58.9-59.1, 59.5 (OCH ₃ - 2 _C D); 50.0 (C-α); 39.7 (C-lα / C-lβ); 37.4 (C-β); 31.9 (C-10α / C-10β); 31.1, 31.4 (Cb, Cc); 29.6 (C-2GC / C- 2β); 29.2-29.7 (C-4α to C-9α / C-4β to C-9β); 26.9 (C-3α / C-3β); 22.6 (C-11α / C-11β); 14.0 (C-12α / C-12β)

Example 4: Preparation of N ', W'-didodécy 1-N _α - (6 ^I -amidosuccinyl-6 ^I -deoxy-2 ^I -0-methyl-hexakis (2 ^{xτ ~ vττ} , 6 ^{ττ ~ vxz} -d ± -0- met yl) cyclomaltoheptaose) -L-glutamide: The title compound, or compound 26, of formula:

26 by coupling the compound 9 synthesized in Example 3 above, with the compound 22 synthesized in Example 2 above. For this coupling, the same protocol _t is followed. as described for the preparation of compound 25 in Example 3 above, but using: - 804 mg (0.57 mmol; 1 eq.) of compound 9 - 355 μL (2.29 mmol; 4 eq .) of DIC - 313.4 mg (2.32 mmol; 4 eq.) of HOBT - 411.8 mg (0.855 mmol; 1.5 eq.) of compound 22. This gives 672.6 g (0, 36 mmol) of compound 26. Crude formula: C ₈ βHi5βN ₄ 0 ₃ 8, M = 1880, 23 g. mol ^-1 Yield: 63% P. f. : 160 ° C (dec.) TLC: R _f = 0.3, eluent: CHCl ₃ / MeOH 8/2 (v / v) [α] _D ²⁰ + 98 ° (c 0.26, CHC1 ₃ )

IR: 3300-3500 cm ^"1 (wide) v (OH); 1655 cm ^-1 v (C = 0 friend of s)

ES-HRMS (high resolution with detection in positive mode): m / z measured at 1902.0529 [M + Na] ⁺ , calculated at 1902.0452 for (deviation: 4.0 ppm) H NMR ^X (CDCl _3, 500.13 MHz) δ (ppm): 7.29 (d, 1H, N H _α); 7.04 (tl, 1H, N'H or N "H); 6.31 (tl, 1H, NH _CD ); 6.05 (t, 1H, N'H or N"H); 4.94-5.06 (m, 7H, H-1 ^I-VII CD); 4.31 (m, 1H, H-CC); 3.82-4.01 (m, H-3 ^I-VII CD); 3.63 (m,

OCH ₃ -6 _CD ); 3.55-3.80 (m, i

3.39-3.52 (m, H-4 ^{I "VII} _CD ); 3.40 (m, OCH ₃ -2 _C D); 3.15-3.33 (m, H-2 ^{I" VII} _CD ); 3.21 (m, H-lα / H-lγ); 2.5-2.6 (m, 4H,

H-b / H-c); 2.46 (m, 1H, H-γ); 2.29 (m, 1H, H-γ '); 2.08 (m, 1H, H-β); 1.99 (m, 1H, H-β '); 1.49 (m, 4H,

H-2α / H-2γ); 1.24-1.32 _% (m, H-3 to H-11α / H-3γ to H-llγ);

0.88 (t, 6H, H-12α / H-12γ)

¹³ C NMR (CDCI ₃ , 125.77 MHz) δ (ppm) 172.9, 172.1, 172.0,

170.9 (4s, -CO-NH); 100.8-101.5 (Cl ^τ'V11 _CD ); 83.0- 83.7, 85.0 (C-4 ^{I "VII} _CD ); 81.7-82.4 (C-2 ^{I" VII} _CD ); 73.0-73.4 _(C _ ₃ I- H _CD) . 69.7-71.7 (C-5 ^{1 "} ^^); 70.5-71.4 (C-6 ^{1" VXI} _C D); 60.1-60.5 (OCH ₃ -6 _CD ); 58.9-59.2, 59.4 (OCH ₃ - 2 _CD ); 52.8 (C-α); 39.7, 39.8 (2s, C-lOC, C-lγ); 32.9 (C-γ); 31.9 (C-10α / C-10γ); 31.4 (Cb / Cc); 29.4 (C-2α / C-2γ); 29.2-29.7 (C-4CX to C-9α / C-4γ to C-9γ); 29.1 (C-β); 27.0, 26.9 (2s, C-30C, C-3γ); 22.6 (C-11α / C-llγ); 14.0 (C-12α / C-12γ) Example 5: Preparation of N ', W "-didodecyl-W _{Q ^} (6 ^I -amidosuccinyl-6 ^I -deoxy-2 ^I , 3 ^I -di-0-methyl-hexakis (2 ^X ~ ^VXX , 3 ^{11 - VI1} , 6 ^{II_VI: ι:} -tri-0-methyl) cyclomaltoheptaose) -L- aspartamide: The title compound, or compound 27, of formula:

27 by coupling 6 ^I -amidosuccinyl-6 ^I -deoxy-2 ¹ , 3 ^x -di-0- methyl-hexakis (2 ^{XI "VI1} , 3 ^{τι ~ VIÏ} , 6 ^II-VII -tri-0-methyl) cyclomaltoheptaose , or compound 13, with compound 21 synthesized in Example 1 above.

5.1. Preparation of compound 13: a) Preparation of 6 ^I -azido-6 ^I -deoxy-2 ^{: ι} :, 3 ¹ -di-

O-methyl-hexakis (2 ^{ιτ ~ vιτ} , 3 ^τι'vτι , 6 ^{ι: E "vι: ι} -tri-0-methyl) cyclomaltoheptaose, or compound 11, of formula:

11 In a dry 500 ml bicol, 6.2 g (0.26 mol; ~ 100 eq.) Of sodium hydride (coated with oil at 60% m / m, ie 10 g of coated material) are introduced. The product is placed under an inert atmosphere, washed with anhydrous hexane (2 x 50 mL) to remove the coating and then dried under a stream of nitrogen. The sodium hydride is then suspended in 130 ml of anhydrous DMF with stirring. 3.01 g (2.60 mmol; 1 eq.) Of compound 3 synthesized in Example 1 above, previously dried in a vacuum oven, are dissolved in 200 ml of anhydrous DMF with stirring and under an inert atmosphere , then added to the reaction medium. The mixture is cooled to 0 ° C. in an ice bath and then 30 mL (0.48 mol; ~ 185 eq.) Of methyl iodide are added. The reaction is stirred for 24 hours at room temperature. The reaction medium is then filtered and the filtrate is concentrated in a rotary evaporator (40 ° C). The oily residue is taken up in a minimum of water and then extracted with chloroform (4 x 40 mL). The organic phase is washed with water (2 x 50 mL), dried over sodium sulfate, filtered, and concentrated in a rotary evaporator (40 ° C). The oily residue is taken up in a minimum of water, the insolubles are filtered and the solution is lyophilized. 3.38 g (2.35 mmol) of a white powder, corresponding to compound 11, and per (2, 3, 6-tri-O-methyl) cyclomaltoheptaose (TRIMEB), formed from the β-CD regenerated during the synthesis of compound 3. This mixture will be purified during the next step (preparation of compound 12). Crude formula: C ₂ Hιo9 ₃ θ34 M = 1440.55 g.mol ^"1

Efficiency: 90%

Mp : 160 ° C (dec.)

TLC: R _f = 0.9 eluent: CHCl ₃ / MeOH 9/1 (v / v)

IR: 2096 cm ^"1 v (N ₃ )

ES-MS +: m / z measured at 1462.8 [M + Na] ⁺ , calculated at 1462.7

^X NMR (CDC1 _3, 500.13 MHz) δ (ppm): 5.31 to 5.36 (H-1 _CD)

3.88-3.96 (H-5CD / H-6 _CD ); 3.69-3.84 (H-4 _CD / H-6 'CD / H-3 _C D)

3.65 (0C £. ₃ -6CD); 3.56 (OCff ₃ -3 _CD ) / ' ³ , 43 (OC. ₃ -2 _CD )

3.38-3.42 (H-2 _CD ) b) Preparation of 6 ^I -amino-6 ^I -deoxy-2 ¹ , 3 ^I -di- O-methyl-hexakis (2 ^{I: L ~ vιτ} , 3 ^{τι ~ vτx} , 6 " ^{~ V]: ι} -tri-0-methyl) cyclomaltoheptaose, or compound 12, of formula:

12 In a 500 mL flask, 3.37 g (2.34 mmol; 1 eq.) Of compound 11 are dissolved in 180 mL of DMF with stirring. A solution of 2.46 g (9.38 mmol; 4 eq.) Of triphenylphosphine (freshly recrystallized from boiling ethanol) dissolved in 10 ml of DMF is added. After 2 hours with stirring at room temperature, the reaction medium is cooled to 0 ° C. in an ice bath and 88.5 ml of ammonia (20% v / v solution) are slowly added. The reaction is maintained for 18 hours with stirring at room temperature. The solution is then concentrated on a rotary evaporator (40 ° C) and the oily residue is taken up in 140 ml of water. The white precipitate formed (mixture of triphenylphosphine and triphenylphosphine oxide) is filtered and washed (2 x 20 ml of water). The filtrate is concentrated under vacuum at 40 ° C, then taken up in a minimum of water and adjusted to pH = 4.5 by addition of a few drops of 1N HCl. This solution is passed over a column of resin exchanger of ions (V = 160 cm ³ ), filled with Lewatit SP 1080 anionic resin, previously regenerated by three successive washing cycles alternating 10% ammonia, water, and 0.1 M HC1. Compound 12 is strongly retained on the column, while that the TRIMEB present is eluted with water (5 column volumes). Compound 12 is in turn eluted with a 10% ammonia solution (3 column volumes). The basic eluate is evaporated to dryness under vacuum (40 ° C); the residue is taken up in a minimum of water and then lyophilized. 1.85 g (1.31 mmol) of compound 12 are thus isolated, in the form of a white powder.

Crude formula: Cg ₂ HmN0 ₃₄ , M = 1414.55 g.mol ^"1 Estimated yield: 86%

Mp : 160 ° C (dec.)

TLC: R _f = 0.7, eluent: CHCl ₃ / MeOH 8/2 (v / v)

IR: Absence of the v band (N ₃ )

ES-MS +: m / z measured at 1414.8 [M + H] ⁺ , calculated at 1414.7 NMR ^X H (D ₂ 0, 500.13 MHz) δ (ppm) 5.36 (d, IH, ^Hl: CD, -2 Ji = 3.6 Hz); 5.30-5.35 (m, 6H, Hl II-VII CD 3.86-

3.96 (m, I H- 5 II-VI CD 3.87-3.92 (m, H- 6 II-VII 3.83

(H-5 ^X CD) 3.75-3.83 (m, H-4 "- ^VII _CD ) 3.76

3.69-3.79 (m, H-3 II-VII CD / 3.71 (H-4 ^I _CD ); 3.65-3.73 (m,

H-ι -, II-VII CDJ 3.64-3.66 (m, OC £. ₃ -6 _C D) 3.55-3.57 (m,

0CH-3 _CD ) 3.43 (H-2 ^I _CD ); 3.42-3.43 (m, 0CH ₃ -2 _CD )

3.36-3.44 (m, H-2 II-VII CD); 3.05 (dd, IH, H-β ¹ ™, e -5 =

5.5 Hz, J ₆ 14.2 Hz); 2.96 (dd, 1H, ³ J _E

= 3.0 Hz, ³ Jgr ^I _ ₆ ^I = 14.2 Hz) 13,

^IJ C NMR (D ₂ 0, 125.77 MHz) δ (ppm) 97.1-97.8 I-VII (CI ^^ _CD ) 10.9-81.6 (C-3 ^I_VII CD); 80.2-80.6 (C-2 ^{I "VII} _CD ); 76.7-78.6 (C-4 ™ _CD ) 71.0-71.4 ; 70.7-71.7 (C-5 ^{1 "}

VII _C D); 59.8-60.4 (OCH ₃ -6 _CD ); 58.3-59.0 (OCH ₃ -3 _CD / OCH ₃ - 2 _CD ); 41.6 (C-6 ^τ _cτ >) c) Preparation of 6 ^I -amidosuccinyl-6 ^I -deoxy- 2 ¹ , S ^ di-Q-methyl-hexakis (2 ^{ττ ~ ylτ} , 3 ^{IX "VI1} , 6 ^{II "VII} -tri-0- methyl) cyclomaltoheptaose, or compound 13, of formula:

13 In a 100 ml flask, 996.7 mg (0.70 mmol; 1 eq.) Of compound 12, previously lyophilized, are dissolved in 20 ml of anhydrous DMF with stirring and under an inert atmosphere. 105.7 mg (1.06 mmol; 1.5 eq.) Of succinic anhydride as solution in 5 ml of anhydrous DMF are then added. The reaction medium is maintained for 18 hours with stirring, under an inert atmosphere and at room temperature. The reaction is stopped by adding 100 μL of water. The solvent is removed using a rotary evaporator (40 ° C), then the residue is taken up in 50 ml of chloroform. The insolubles (succinic acid) are filtered on a 0.22 μm Teflon filter and the chloroform is evaporated to dryness under vacuum (40 ° C). The residue is taken up in a minimum of water and lyophilized. 1.03 g (0.68 mmol) of compound 13 is obtained, in the form of a white powder.

Crude formula: C ₆ gHιι ₅ N0 ₃ 7, M = 1514.62 g.mol ^"1 Yield: 96%

Mp : 160 ° C (dec.)

TLC: R _f = 0.6 eluent: CH ₂ Cl ₂ / MeOH 9/1 (v / v)

IR: 1733 cm ^-1 V (C = 0 acid); 1676 cm ^"1 v (C = 0 amide)

ES-MS +: m / z measured at 1536.9 [M + Na] ⁺ , calculated at 1536.7 for CggHn ₅ 0 ₃₇ Na

RMN ^X R (CDC1 ₃ , 500.13 MHz) δ (ppm) 6.40 (t, 1H, NH _CD ,

³ J _N H-6 ^I = 5.6 Hz); 5.24, 5.22, 5.14, 5.11, 5.07, 5.07 (6d, H-1 ^II ~ ^VII CD, ³ Jι-2 = 3.7 Hz); 5.08 (d, ³ JI ^I - ₂ ^I =

3.7 Hz); 3.85 - 3.95 (m, H-6 ^II-VII _CD ); 3.87 (HS ¹ ^); 3.86, 3.73, 3.78, 3.87, 3.82, 3.79 (H-5 ^II-VII _CD ); 3.77 (H-6 ^X CD); 3.62-3.68 (m, OCH ₃ -6 _C D); 3.63, 3.63, 3.63, 3.60, 3.62, 3.70 (H-4 ^II_VII CD); 3.55-3.65 (H-6 ' ^II_VII _C D); 3.57 (H ^ _C D) 3.46, 3.57, 3.56, 3.50, 3.50, 3.44 (H-3 ^II-VII CD); 3.49-3.53 (m, OCH ₃ -3 _C D); 3.38-3.42 (m, 0Cff ₃ -2c _D ) 3.36 (H-4 ^I _CD ); 3.35 (H-6 ' ^X _C D); 3,20, 3.19, 3.18, 3.18, 3.18, 3.18 (H-2 ^II_VII _CD ); 3.18 (H-2 ^I _CD ); 2.74, 2.65, 2.49 (4H, Hb / Hc, AA'B system)

¹³ C NMR (CDCl ₃ , 125.77 MHz) δ (ppm) 174.5 (Cd); 172.7 (Ca); 98.7-99.9 (7s, C-1 ^{I ~ "VII} _CD ); 82.0-82.9 (C-3 ^1"

^VII CD / C-2 ^{I "VII} CD); 79.6-81.4 (C-4 ^I - ^VII _CD ); 71.5-72.2 (C-6 ^11"

^VII CD); 70.7-71.9 (C-5 ^I_VII CD); 61.7-62.3 (OCH ₃ -6 _CD );

58.9-60.1 (0CH ₃ -3CD / 0CH ₃ -2 _C D); 42.0 (C-6 ^I _C D); 31.5, 30.5 (Cb, Cc) 5.2. Preparation of compound 27: In a dry 100 ml three-necked flask, 1.01 g (0.67 mmol; 1 eq.) Of compound 13, previously lyophilized, are dissolved in 15 ml of anhydrous DMF with stirring and under an inert atmosphere. 415 μL (2.68 mmol; 4 eq.) Of DIC then 361.4 mg (2.68 mmol; 4 eq.) Of HOBT, in solution in 5 ml of anhydrous DMF, are successively added. The reaction is then maintained for 2 hours with stirring and under an inert atmosphere at room temperature. 376.1 mg (0.80 mmol; 1.2 eq.) Of the compound

21, dissolved in 20 ml of anhydrous chloroform (freshly distilled on P2O ₅ ), are added to the reaction medium. After 24 hours of stirring at room temperature and under an inert atmosphere, the reaction is stopped by adding 100 μL of water. The solution is evaporated to dryness under primary vacuum (40 ° C), the residue is taken up in 20 ml of chloroform and the insolubles are filtered. The filtrate is concentrated on a rotary evaporator (30 ° C) and purified using a chromatographic column on silica gel 60 Fluka (elution with CHC1 ₃ / CH ₃ 0H 99/1 then 98/2 then 95/5 (v / v)). We thus isolates 605 mg (0.31 mmol) of compound 27 in the form of a white powder after lyophilization.

Crude formula: C ₉₄ Hi7oN4θ ₃₈ , M = 1964.39 g.mol ^"1 Yield: 46%

Mp : 160 ° C (dec.)

TLC: R _f = 0.4 eluent: CHCl ₃ / MeOH 95/5 (v / v)

[α] _D ²⁰ + 107 ° (c 0.27, CHC1 ₃ )

IR: / Absence of v (OH) band; 1651 cm ^"1 (C = 0 amides) ES-HRMS (high resolution with detection in positive mode): m / z measured at 1986.1432 [M + Na] ⁺ , calculated at 1986.1391 for C ₉₄ Hι ₇₀ N ₄ θ ₃₈ Na (deviation 2.1 ppm) ΕL NMR (CDC1 _3, 500.13 MHz) δ (ppm): 7.56 (t, IH, N H or N "H); 7.45 (d, 1H, N _α iî); 6.37 (t, 1H, N'H or N "H); 6.16 (t, 1H, NH _C D); 5.08-5.17 (m, Hl ^1" ^^); 4.65 (m,

H-); 3.70 to 3.90 ; 3.4-3.7 (H-4 ^{11 "} ; 3.63 (m, OCH ₃ -6 _CD); 3.42-3.56 (H-3 ^{1 "}

^VII CD); 3.50 (m, 0Ci? 3-3 _CD ); 3.38 (m, 0CH ₃ -2 _CD ); 3.36 (H-4 ^I _CD ); 3.12-3.24 (H-2 ^I-VII CD); 3.18 (m, H-lα / H-lβ); 2.87 (dd, 1H, H-β); 2.4-2.7 (m, 4H, Hb / Hc); 2.43 (dd, 1H, H-β '); 1.47 (m, H-2α / H-2β); 1.23-1.31 (m,

H-3α to H-11α / H-3β to H-11β); 0.87 (t, 6H, H-120C / H-12β)

¹³ C NMR (CDCI ₃ , 125.77 MHz) δ (ppm): 170.3, 171.1,

171.8, 171.9 (4s, -CO-NH); 98.0-99.2 (C-1 ^I-VII _C D); 79.1-82.3 (C-3 ^{I "VII} CD / C-2 ^{I" VII} _C D / C-4 ^{I "VII} CD); 70.5-71.5 _(C _ ₆ II-VII _{CD / C} _ ₅ II-VII _CD) . ₇₀ ^ _{0 {c} _ ₅ i _CD ) _; 61.0-61.6 (OCH ₃ -

6CD); 58.0-59.5 (0CH ₃ -2 _C D / 0CH ₃ -3CD); 49.9 (C-α); 40.1 (C-6 ^∑ _C D); 39.6 (C-lα / C-lβ); 37.3 (C-β); 31.8 (C-10α / C-10β); 31.0, 31.4 (Cb, Cc); 29.0-29.7 (C-4α àC-9α / C-4β to C-9β); 26.8 (C-3α / C-3β); 22.5

(C-11α / C-11β); 14.0 (C-12α / C-12β)

Example 6 Preparation of W-dodecyl-W'-hexadecyl-WOr (6 ^I -amidosuccinyl-6 ^I -deoxy-cyclomaltoheptaose) -L- aspartamide: The title compound, or compound 33, of formula:

33 by coupling the compound 5 'synthesized in Example 1 above with the'-dodecyl-W'-hexadecyl-L-aspartamide, or compound 32.

6.1. Preparation of compound 32: a) Preparation of AT'-dodecyl-Zv ^" " - (tert-butyl-oxycarbonyl) -N _a - (9-fluorenylmethoxycarbonyl) -L- aspartamide, or compound 29, of formula:

29 In a dry 100 mL flask, 504.7 mg (1.23 mmol; 1 eq.) Of N "- (tert-butyloxycarbonyl) - JV _α - (9-fluorenylmethoxycarbonyl) -L-Aspartic acid (Fluka) are dissolved in 5 ml of anhydrous DMF with stirring and under an inert atmosphere 285 μL (1.84 mmol; 1.5 eq.) of DIC then 249.5 mg (1.85 mmol; 1.5 eq.) of HOBT dissolved in 1 ml of anhydrous DMF, are successively added.The reaction is then maintained for 2 hours with stirring and under an inert atmosphere at room temperature 344.2 mg (1.86 mmol; 1.5 eq.) Of dodecyla ine , in solution in 20 mL of anhydrous chloroform, are finally added to the reaction medium After 18 hours of stirring at room temperature and under an inert atmosphere, the reaction is stopped by adding 100 μL of water. The solution is evaporated to dryness under primary vacuum (40 ° C.), the residue is taken up in 20 ml of chloroform and the insolubles are filtered, the filtrate is concentrated in a rotary evaporator (30 ° C.) and purified using a chromatographic column on silica gel 60 Fluka (elution with CHC1 ₃ + AcOH (0.2%)). The eluate is evaporated to dryness and the residue taken up in a minimum of methanol. Compound 29 is then precipitated by adding 50 ml of water. The solid is filtered on sintered glass and washed with water. After drying overnight in a vacuum oven, 619.4 mg (1.07 mmol) of compound 29 are isolated, in the form of a white powder.

Crude formula: C ₃₅ H ₅ oN ₂ 0 ₅ , M = 578.79 g. mol ^"1 Yield: 87%

IR: 3349 cm ^"1 (wide) v (NH-amide); 1744 cm ^{" 1} V (C = 0 ester); 1701 cm ^-1 V (C = 0 carbamate); 1646 cm ^"1 V (C = 0 amide) ESI-MS +: m / z measured at 601.5 [M + Na] ⁺ , calculated at 601.4 for C ₃₅ H ₅ oN ₂ 0 ₅ Na

NMR ^X R (CDC1 ₃ , 500.13 MHz) δ (ppm): 7.77 (d, 2H, H-4 / H- 4 ', ³ J ₄ -3 = ³ J4 <-3 <= 7.5 , Hz); 7.62 (d, Hl, ³ Jι_ ₂ = 7.5 Hz); 7.61 (d, H-l ', ³ ϋ - ₂ ' = 7.5 Hz); 7.41 (t, 2H, H-3 / H-3 ', ³ J ₃ - ₂ = ³ J ₃ _ ₄ = ³ J _3' - ₂ '= ³ J _3' -4 '= 7.5 Hz) ; 7.32 (t, 2H, H-2 / H-2 ', ³ J ₂ -ι = ³ J ₂ -3 = ³ J _2' -ι <= ³ J _{2 '} -3' = 7.5

Hz); 6.09 (d, 1H, N _α H, ³ J _NαH - = 8.3 Hz); 5.62 (tl, 1H,

If); 4.48 (m, 1H, H-α); 4.40 (dd, 1H, H-8); 4.32 (dd, 1H, H-8 '); 4.23 (t, 1H, H-7); 3.24 (m, 2H, H-1α); 2.87 (dd, 1H, H-β, ³ J _β - _β > = 15.5 Hz, ³ Jβ- "= 5.1 Hz); 2.71 (dd, 1H, H-β ', ³ Jβ'-β = 15.5 Hz, ³ Jβ <- _α = 4.3 Hz); 1.49 (s, 3 ^χ CE ₃ tBu); 1.47 (m, H-2α); 1.24-1.32 (m, 18H, H-3α to H-11α); 0.89 (t, 3H, H-12α, ³ Jι _2α -ιι = 6.8 Hz) ¹³ C NMR (CHC1 ₃ , 125.77 MHz) δ (ppm): 170.7 (-CO-N'H); 170.3 (-CO-OtBu); 156.9 (C-10); 144.6, 144.5 (C-5, C-5 '); 141.9 (C-6 / C-6 '); 128.4 (C-3 / C-3 '); 127.7 (C-2 / C-2 '); 125.9 (Cl / C-1 '); 120.6 (C-4 / C-4 '); 83.0 (-C-tBu); 67.9 (C-8); 52.1 (C-α); 47.8 (C-7); 40.3 (C-1α); 38.8 (C-β); 32.6 (C-10α); 29.9-30.4, C-4α to C-9α); 30.0 (C-2α); 28.6 (3xCH3 tBu); 27.6 (C-3α); 23.4 (C-11α); 14.8 (C-12α) b) Preparation of N '-dodecyl-Ng- (9-fluorenylmethoxycarbonyl) -L-aspartamide, or compound 30, of formula:

In a 50 mL flask, 542.6 mg (0.94 mmol; 1 eq.) Of compound 29 is dissolved in 10 mL of a 20% (v / v) solution of trifluoroacetic acid in the dichloromethane. The reaction medium is kept stirring for 3 hours at room temperature. The solution is then evaporated to dryness under primary vacuum (30 ° C). The residue is taken up in a minimum of ethyl acetate and precipitated by adding 40 ml of petroleum ether. After having allowed to settle for 2 hours at 4 ° C., the precipitate is filtered through sintered glass and then dried overnight in a vacuum oven. We obtains 461.7 mg (0.88 mmol) of compound 30 in the form of a white powder.

Crude formula: C ₃ ιH ₂ N ₂ 0 ₅ , M = 522.68 g.mol ^-1 Yield: 94%

Mp : 155 ° C

TLC: R _f = 0.1 eluent: CHCl ₃ / MeOH 9/1 (v / v)

IR: 3306 cm ^"1 (wide) V (NH-amide); 1703 cm ^-1 (2s)

V (C = 0 acid) and v (C = 0 carbamate); 1645 cm ^-1 V (C = 0 amide)

ESI-MS +: m / z measured at 545.5 [M + Na] ⁺ , calculated at 545.3

NMR ^ Η (DMSO-d6, 500.13 MHz) δ (ppm): 12.8 (if,

-COOfl); 7.99 (d, 2H, H-4 / H-4 ', ³ J ₄ - ₃ = ³ J ₄ ' -3 '= 7.5 Hz); 7.92 (bt, 1H, N'H); 7.80 (d, 2H, Hl / H-1 ', ³ Jι- ₂

= ³ Ji'_ ₂ '= 7.5 Hz); 7.64 (d, 1H, N "H, ³ J _N αH-α = 8.3 Hz);

7.51 (t, 2H, H-3 / H-3 ', ³ J ₃ - ₂ = ³ J ₃ - ₄ = ³ J ₃ ' -2 '= ³ J ₃ ' -4 '= 7.5

Hz) 7.42 (t, 2H, H-2 / H-2 'J2-1 - J2-3 - J2' - J2'-3

= 7.5 Hz); 4.46 (dt, 1H, H-α, ^J _α - _NH = J -β '= 8.3 Hz, ³ J _α -β = 5.2 Hz); 4.34 (H-8); 4.31 (H-7); 3.12 (m, 2H,

H-1α); 2.67 (dd, IH, H-β, ³ Jβ-β> = 15 Hz, ³ Jβ_ _α = 5.2

Hz); 2.57 (dd, IH, H-β ', ³ Jβ'-β = 15 Hz, ³ Jβ'_ _α = 8.3

Hz); 1.45 (m, 2H, H-2α); 1.28-1.36 (m, 18H,

H-3α to H-11α); 0.94 (t, 3H, H-12α, ³ Jι ₂ α-uα = 6.8 Hz) ¹³ C NMR (DMSO-d6, 125.77 MHz) δ (ppm): 173.1 (-COOH);

168.8 (-CO-N'H); 155.7 (C-10); 143.7 (C-5 / C-5 ');

140.7 (C-6 / C-6 '); 127, 6 (C-3 / C-3 '); 127.0 (C-2 / C-

2 '); 125.2 (Cl / C-1 '); 120.1 (C-4 / C-4 '); 65.7 (C-8); 50.7 (C-α); 46.6 (C-7); 38.6 (C-1α); 37.0 (C-β); 31, 3 (C-10G6); 28, 6-29, 1 (C-2CC, C-4α to C-9α); 26, 3 (C-3α); 22, 1 (C-11α); 13, 9 (C-12α) c) Preparation of N -dodecyl-N "-hexadecyl-N - (9-fluorenylmethoxycarbonyl) -L-aspartamide, or compound 31, of formula:

31 In a dry 50 mL flask, 396.0 mg (0.76 mmol; 1 eq.) Of compound 30 is dissolved in

5 mL of anhydrous DMF with stirring and under an inert atmosphere. 176 μL (1.14 mmol; 1.5 eq.) Of DIC then

155.2 mg (1.15 mmol; 1.5 eq.) Of HOBT dissolved in 1 ml of anhydrous DMF are successively added. The reaction is then maintained for 2 hours with stirring and under an inert atmosphere at room temperature. 276.9 mg (1.15 mmol; 1.5 eq.) Of hexadecylamine, dissolved in 20 ml of anhydrous chloroform, are added to the reaction medium and the whole is left for 24 hours, with stirring and under atmosphere inert, at room temperature (an abundant precipitate forms quickly). The mixture is then concentrated in a rotary evaporator (40 ° C) and taken up in DMF. The pasty solid is filtered through a sintered glass and washed, first with DMF, then with ether. After overnight drying in a vacuum oven, 335.7 mg (0.46 mmol) of compound 31 is isolated, in the form of a fine white powder.

Crude formula: C ₄₇ H _{75 3} 0 ₄ , M = 746.13 g.mol ^"1 Yield: 61%

TLC: R _f = 0.85 eluent: CHCl ₃ / MeOH 95/5 (v / v) d) Preparation of '-dodecyl-W'-hexadecyl-L- aspartamide, or compound 32, of formula:

32 In a 50 mL flask, 330 mg (0.44 mmol; 1 eq.) Of compound 31 are dissolved in 10 mL of a 20% (v / v) solution of piperidine in chloroform. The solution is heated for a few minutes at 40 ° C. The reaction medium, initially heterogeneous because of the low solubility of the starting product in chloroform, quickly becomes clear. The solution is then evaporated to dryness, under primary vacuum (40 ° C), to eliminate the maximum of piperidine (bp 101-106 ° C). The solid residue is taken up in 1 L of chloroform to then be precipitated in 100 mL of hexane with stirring. After having allowed to settle for 2 hours at 4 ° C., the precipitate is recovered by centrifugation (10,000 rpm, 20 min). The solid is dried, then a final stage of recrystallization from methanol (dissolution in a minimum of boiling methanol, filtration of the insoluble materials in the hot state and recrystallization at 4 ° C.) makes it possible to isolate by filtration, and after drying overnight at l vacuum oven, 196 mg (0.37 mmol) of compound 32 in the form of a white powdery powder.

Crude formula: C ₃ 2H ₅ N3θ ₂ , M = 523.89 g.mol ^-1 Yield: 84% mp: 104 ° C

TLC: R _f = 0.5 eluent: CHCl ₃ / MeOH 9/1 (v / v)

IR: 3315 cm ^-1 (wide) V (NH-amide) and v (NH ₂ );

1631 cm ^"1 V (C = 0 amide)

ESI-MS +: / z measured at 524.6 [M + Na] ⁺ , calculated at 524.5 for C ₃₂ Hg ₃ 0 ₂

RMN ^X R (CDC1 ₃ , 500.13 MHz) δ (ppm): 7.50 (tl, 1H,

N'H); 6.23 (tl, 1H, N "H); 3.65 (m, 1H, H-α); 3.21 (m, 4H, H-1α / H-1β); 2.61 (dd, 1H , H-β); 2.55 (dd, 1H,

H-β '); 1.48 (m, 4H, H-2α / H-2β); 1.24-1.32 (m, 44 H, H-3α to H-11α / H-3β to H-15β); 0.88 (t, 6H, H-12α / H-16β)

¹³ C NMR (CDCI ₃ , 125.77 MHz) δ (ppm): 174.4 (CO-N'H);

171.6 (C0 ~ N "H); 53.5 (C-0C); 41.7 (C-β); 40.2, 40.0 (C-lα, C-lβ); 32.6 ( C-10α / C-14β); 30.2-30.4

(C-40C to C-9α, C-4β to C-13β); 30.0 (2s, C-2α / C-2β); 27.6 (2s, C-3α / C-3β); 23.4 (C-11α / C-15β); 14.8 (C-12α / C-16β)

6.2. Preparation of compound 33: The coupling of compounds 5 and 32 is carried out by following the same experimental protocol as that described for the preparation of compound 23 in Example 1 above, but using: - 191.6 mg (0, 16 mmol; 1 eq.) Of compound 5 - 96 μL (0.62 mmol; 4 eq.) Of DIC - 86.0 mg (0.64 mmol; 4 eq.) Of HOBT - 122.9 mg (0, 23 mmol; 1.5 eq.) Of compound 32. This gives 178 mg (0.10 mmol) of compound 33.

Crude formula: C ₇₈ Hι ₃₈ N ₄ 0 ₃ s, M = 1739.96 g. mol ^-1

Yield: 66%

Mp : 160 ° C (dec.)

TLC: R _f = 0.2 eluent: CHCl ₃ / MeOH / H ₂ 0 6/3 / 0.5 (v / v / v) [α] _D ²⁰ + 80 ° (c 0.26, DMF)

IR: 3000-3500 cm ^"1 (wide) V (OH); 1652 cm ^{" 1} v (C = 0 friend of s)

ES-HRMS (high resolution with detection in positive mode): m / z measured at [M + H] ⁺ , calculated at 1739.9067

NMR ^X R (pyridine-ds, 500.13 MHz) δ (ppm): 9.17 (d, 1H,

N _D H); 8.82 (t, 1H, Nf. _CD ); 8.56 (t, 1H, N "fl); 8.37 (t,

IH, N'A); 4.94 (m, 1H, H-α); 5.56-5.60 (m), 5.55 (d), 5.46 (d) (6H, H-1 ^II_VII CD); 5.43 (d, 1H, HI ^ _D ); 4.62-4.76 (m, H-3 ^II-VII CD); 4.62 (H-3 ^∑ C _D ); 4.56-4.64 (m, _H _ ₆ "- II _CD) . 4.28-4.53 (m, H-5 ^XI - ^VII _C D / H-6 ' ^II_VII _C D); 4.41 -5 ^τ _CO ); 4.14- 4.27 (m, H-4 ^{II "VII} _CD ); 4.19 (H-6 ^X _C D); 4.06

(H-6 ^rI cD); 3.98-4.13 (m, H-2 ^II'_VII CD); 3.92 (dd, 1H,

H-2 ^r _CD ); 3.80 (t, 1H, H-4 ^I _CD ); 3.35, 3.30 (m, 4H, H-lα, H-lγ); 2.6-3.0 (m, Hb / Hc); 2.61 (m, H-γ / H-γ '); 2.61 (m, H-β); 2.34 (m, 1H, H-β '); 1.50, 1.47 (m, 4H,

H-2α, H-2γ); 1.18 (H-3α / H-3γ); 1.05-1.25 (m,

H-4α to H-llα / H-4γ to H-llγ); 0.75 (t, 6H, H-12α / H-12γ)

¹³ C NMR (pyridine-ds, 125.77 MHz) δ (ppm): 173.7 (Ca); 173.6 (Cd); 173.2 (-CO-N'H); 172.9 (-CO-

N "H); 104.1-104.6 (C-1 ^1-VII _C D); 85.8 (C-4 ^I _CD ); 83.8-

84.2 (C-4 ^II_VII _CD ); 74.1-75.4 (C-3 ^I ~ ^VII _CD / C-5 ^{II "V1I} _CD / C-2 ^I"

^VII _C D); 72.3 (C-δ ^ o); 62.7 (C-6 ^X CD); 62.0-62.3 (C-6 ^11-

^VII _C D); 41.6 (C-α); 40.3 (C-lα / C-lγ); 33.8 (C-γ); 32.6 (C-10α / C-10γ); 32.1, 32.3 (Cb, Cc); 30.5 (C-2α / C-2γ); 30.1 (C-4α / C-4γ); 30.1-30.7 (C-5α to C-9α / C-5γ to C-9γ); 30.0 (C- ^); 27.8, 27.9 (C-3α, C-3γ); 23.4 (C-llα / C-llγ); 14.8 (C-12α / C-12γ)

Example 7: Preparation of N ', N "-didodecyl-N _a r (6 ^I -amidosuccinyl-6 ^I -deoxy-2 ^I , 3 ^I -di-0-methyl-hexakis (2 ^{XX ~ VXX} , 3 ^{XX ~ VI1} , 6 ^II_VII -tri-0-methyl) cyclomaltoheptaose) -L-glutamide: The title compound, or compound 9a, of formula is obtained

9a by coupling 6 ^I -amidosuccinyl-6 ^I -deoxy-2 ¹ , 3 ^I -di-0- methyl-hexakis (2 ^II_VI1 , 3 ^II_VI1 , 6 ^II_VII -tri-0-methyl) cyclo-maltoheptaose, or compound 13 synthesized in Example 5 above, with W ', Zv ^" " -didodecyl-L-glutamide, or compound 22 synthesized in Example 2 above, but using: - 1.01 g (0, 67 mmol; 1 eq.) Of compound 13 - 415 μl (2.68 mmol, 4 eq.) Of DIC - 361.4 mg (2.68 mmol; 4 eq.) Of HOBT - 376.1 mg (0.80 mmol; 1.2 eq.) of compound 22. This gives 605 mg (0.31 mmol, 46% yield) of compound 9a. Example 8: Preparation of N ', N "-dihexadecyl-.N _Q r (6 ¹ - amidosuccinyl-6 ^I -deoxy-2 ^:!: , 3 ^I -di-0-methyl-hexakis (2 ^{II_ ra} , 3 ^II_VI1 , 6 ^II_VII -tri-0-methyl) cyclomaltoheptaose) -L- aspartamide: The title compound, or compound 9b, of formula:

9b by coupling the compound 13 synthesized in Example 5 above with N ', W-dihexadecyl-L-aspartamide, or compound 8b. ..

8.1. Preparation of compound 8b: a) Preparation of N ', Àr'-dihexadecyl-Ng- (9-fluorenylmethoxycarbonyl) -L-aspartamide, or compound 7b, of formula:

7b In a 250 ml flask, the compound 17 synthesized in Example 1 above (1.5 g, 4.22 mmol, 1 eq.) Is dissolved in 10 ml of DMF, 2 ml (3 eq.) of DIC then 1.71 g of hydrated HOBT (3 eq.) dissolved in 8 ml of DMF are successively added. The reaction medium is kept stirring for 3 hours 30 minutes. A solution of hexadecylamine (3.06 g, 12.6 mmol, 3 eq.) In 70 ml of CHC1 ₃ is then added and the reaction medium is left at room temperature for 48 hours. The mixture is concentrated in vacuo, taken up in DMF. The precipitate is filtered, washed with DMF and then with ether. Finally, the solid is dried under vacuum. Compound 7b is obtained with a yield of 81%.

TLC: R _f ≈ 0.9 eluent: CHCl ₃ / MeOH 95/5 (v / v)

Mp : 189 ° C

NMR ^X R CDC1 ₃ δ (ppm): 7.78 (d, 2H, H ₄ / H ₄ <, ³ J ₄ -3 = ³ J4'-3 '= 7.5 Hz); 7.60 (d, 2H, Hι / H, ³ Jι- ₂ = ³ Jι-- '= 7.5

Hz); 7.35 (m, 4H, H ₂ / H ₂ "/ H ₃ / H3 '); 6.98 (bt, 1H, N'H);

6.5 (d, 1H, N _α H); 5.75 (tl, 1H, N "H); 4.4-4.3 (m,

H _α / H ₈ ); 4.21 (t, 1H, H ₇ , ³ J ₇ -s = 7.2 Hz); 3.23 (m, 4H,

Hiα / Hiβ); 2.75 (d, 1H, Hβ, ³ Jβ-β- = 15 Hz); 2.5 (dd, 1H, Hβ., ³ Jβ-β '= 15 Hz, ³ J _α _ _β , = 7 Hz); 1.5 (m, 4H, H _2α / H ₂ β);

1.4-1.1 (m, H _3α to Hι _5α / H ₃ β to Hisβ); 0.9 (t, 6H, Hι _6α / Hι ₆ β) b) Preparation of compound 8b

8b In a 250 mL flask, compound 7b (1.42 g, 3.02 mmol, 1 eq.) Is dissolved in 93 mL of 20% piperidine in chloroform. The reaction medium is maintained at 40 ° C for 3 hours then evaporated to dryness and finally taken up in 120 ml of chloroform. 300 mL of hexane are added and the precipitate formed placed in the refrigerator overnight then filtered. An ethanol wash is carried out in order to remove the traces of piperidine. After drying in a desiccator, compound 8b is obtained with 86% yield.

TLC: R _f = 0.45 eluent: CHCl ₃ / MeOH 95/5 (v / v)

Mp : 120 ° C

NMR R CDC1 ₃ δ (ppm): 7.5 (tl, 1H, N'H); 6.15 (tl, 1H,

N "H); 3.65 (t, H _α , ³ J -β = ³ J -β '= 7 Hz ^' ); 3.2 (m, 4H,

Hio / Hiβ); 2.6 (m, 2H, H _β , Hβ; 1.6-1.1 (m, H _2α to Hι _6α / H ₂ β to Higβ); 0.87 (t, 6H, Hιg _α / Hιgβ)

NMR 13, C CDCI3 δ (ppm): 174.6 (-CO-N'H); 171.7 (-CO-

N "H); 53.8 (c-α) 42.03 (C-β) 40.4-40.2 (C-lα, C-lβ); 32, 7 (C-140C / C-14β); 30, 5-30, 2 (C-20C, C-4α to C-13α / C-2β, C-4β to C-13β); 27.8 (C-3CC / C-3β); 23.5 (C-15α / C-15β); 14, 95 (C-16α / C-16β) 8.2. Preparation of compound 9b: In a 100 mL flask, compound 13 (500 mg, 0.33 mmol, 1 eq.) Is dissolved in 15 ml of DMF, 90 μL (2 eq.) Of DIC then 50 mg (2 eq.) of HOBT dissolved in 4 mL of chloroform are successively added. After 2 hours 30 minutes at room temperature, ii of equivalent of each of the reactants is added so that all of the compound 13 is consumed. After 1 hour, compound 8b (287 mg, 0.5 mmol, 1.2 eq.), Dissolved in 40 ml of chloroform, is added. After 24 hours at room temperature, the reaction is stopped with 100 μL of water and the reaction medium is concentrated to dryness on a rotary evaporator. The crude product obtained is passed through a column of chromatography on silica gel 60 Fluka (eluent gradient: CHCl ₃ / MeOH: 99/1, 97/3 and 95/5). After evaporation of all the pure fractions, compound 9b is obtained with 30% yield.

Example 9 Preparation of N'-dodecyl-Nor (6 ¹ -amidosuccinyl-6 ^I -deoxy-2 ^I , 3 ^I -di-0-methyl-hexakis (2 ^{II_ TO} , 3 ^II_VI1 , 6 ^II_VII -tri- -methyl ) cyclomaltoheptaose) -L- leucina ide: The title compound, or compound 9c, of formula:

9c by coupling the compound 13 synthesized in Example 5 above with N'-dodecyl-L-Leucinamide, or compound 21a.

9.1. Preparation of compound 21a: a) Preparation of N - (9-fluorenylmethoxycarbonyl) -L-Leucine, or compound 17a, of formula:

17a Compound 17a is prepared by following the same experimental protocol as that described for the preparation of 17 in Example 1 but using: - 3.64 g (35 mmol, 1 eq.) Of L-leucine - 83 mL (105 mmol, 3.6 eq.) of an aqueous sodium carbonate solution at 13% (m / v), and - 9.84 g (29.16 mmol, 1 eq) of N-Finoc. 8.9 g (27.30 mmol, 93% yield) are thus obtained of compound 17a. b) Preparation of N ^f -dodecyl-N _α - (9-fluorenylmethoxycarbonyl) -L-leucinamide, or compound 19a, of formula:

19a Compound 19a is prepared by following the same experimental protocol as that described for the preparation of compound 19 in example 1 but using: - 6.84 g (21 mmol, 1 eq.) Of compound 17a - 9.8 mL (63 mmol, 3 eq.) DIC - 8.5 g (63 mmol, 3 eq.) HOBT - 11.67 (63 mmol, 3 eq.) dodecylamine. 7.25 g (14.70 mmol, yield of 70%) of compound 19a are thus obtained. c) Preparation of '-dodecyl-L-leucinamide, or compound 21a, of formula:

21a The compound 21a is prepared by following the same experimental protocol as that described for the preparation of 21 in Example 1 above but using 8.2 g (16.6 mmol, 1 eq.) Of the compound 19a. 3.6 g (13.3 mmol, 80% yield) of compound 21a are thus obtained.

9.2. Preparation of compound 9c: In a 50 ml flask, compound 13 (427 mg, 0.28 mmol, 1 eq.) Is dissolved in 15 ml of

DMF, 108 μL (2.5 eq.) Of DIC then 70 mg (2.5 eq.) Of

HOBT dissolved in 1 mL of DMF are successively added. After 2 hours at room temperature, 0.25 equivalent of each of the reactants is added so that all of the compound 13 is consumed. After 1 hour, compound 21a (100 mg, 0.33 mmol, 1.2 eq.), Dissolved in

7 ml of chloroform is added. After 18 hours at room temperature, the reaction is stopped with

100 μL of water and the reaction medium is concentrated to dryness on a rotary evaporator. The crude product obtained is passed through a gel chromatography column. silica 60 Fluka (elution gradient: CHCl ₃ / MeOH: 99/1 (v / v) then 97/3 (v / v)).

Example 10: Preparation of N ^r , N "~ dodecyl-N _a - (6 ¹ - amidosuccinyl-6 ^I- deoxy-per (2, 3, 6-di-O-methyl) cyclomaltoheptaose) -β-alanine: On obtains the title compound, or compound 9d, of formula:

9d by coupling 6 ^I -amidosuccinyl-6 ^I -deoxy-per (2, 3, 6-tri- O-methyl) cyclomaltoheptaose, or compound 5a, with N-dodecyl-jNO- (9-f luorenylmethoxycarbonyl) -β -alanine, or compound 7c.

10.1. Preparation of compound 5a: a) Preparation of 6 ^I -azido-6 ^I -deoxy- per (2, 3, 6-tri-Q-methyl) cyclomaltoheptaose, or compound 3a, of formula:

3a In a clean, dry bicol, sodium hydride (coated at 60% m / m) (11.01 g, 0.46 mol, 88 eq.) Is suspended in 150 ml of anhydrous DMF and under inert atmosphere. A solution obtained by dissolving compound 3 (3.64 g, 0.0031 mol, 1 eq.) Synthesized in example 1 in 240 ml of anhydrous DMF, is added under an inert atmosphere and at room temperature. After 1 hour 30 minutes, the reaction medium is cooled to 0 ° C. and methyl iodide (38 mL, 0.6 mol, 190 eq.) Is added dropwise. The reaction medium is left at room temperature for 72 hours then the reaction is stopped with 6 ml of water. The precipitate formed is filtered and washed with DMF. The filtrate is concentrated on a rotary evaporator. The pasty residue is taken up in water and extracted with chloroform (5 x 50 mL). The organic phase is washed with water (3 x 100 mL). The organic phases are combined, dried over Na ₂ Sθ4, filtered and then evaporated. The residue is taken up a last time in water and left to settle overnight to remove the fat containing sodium hydride. After evaporation and lyophilization, compound 3a is obtained with a quantitative yield.

TLC: R _f = 0.9 eluent: CHCl ₃ / MeOH 9/1 (v / v) Mp: 80 ° C (decomposition)

RMN R CDC1 ₃ δ (ppm): 5.2-5 (m. 7H, Hi-CD); 4-3.25 (m,

H ₃ -CD / H ₄ -CD / H5-CD / Hg-CD / Hg _' -CD / OCH ₃ -CD) 3.25-3.1 (dd, 7H, H ₂ -CD, ³ Jι_ ₂ = 10 Hz / ³ J ₂ - ₃ = 4 Hz) b) Preparation of 6 ^I -amino-6 ^I -deoxy- per (2, 3, 6-tri-O-methyl) cyclomaltoheptaose, or compound

4a, of formula

4a In a 1 liter flask, compound 3a (4.33 g, 3mmol, 1 eq.) Is dissolved in 220 ml of DMF. A solution of triphenylphosphine (3.15 g, 0.012 mol, 4 eq.) Dissolved in 13 ml of DMF is added slowly. After 3 hours with stirring at room temperature, the reaction medium is cooled to 0 ° C and 115 ml of 20% ammonia are added. This is stirred overnight at room temperature and then concentrated in a rotary evaporator. The oily residue is taken up in 250 ml of water, the white precipitate formed is filtered, washed with 2 x 40 ml of water. The filtrate is then concentrated in vacuo, the solid residue is taken up in a minimum of water and then brought to a pH of 4.5 (initial pH = 8.2), the insolubles are filtered and the filtrate is passed through a column of Lewatit SP 1080 resin Compound 4a is removed with 6% ammonia then the filtrate is concentrated with a rotary evaporator, taken up in a minimum of water and then lyophilized. Compound 4a is obtained with an overall yield of 60%.

TLC: R _f = 0.25 eluent: CHCl ₃ / MeOH 95/5 (v / v)

Mp : 80 ° C (decomposition)

RMN ^X R (CDC1 ₃ , 500.13 MHz) δ (ppm): 5.36 (d, IH, HI ^ D,

³ Jι ^I _2 ^I = 3.6 Hz); 5.30-5.35 (m, 6H, H-1 ^II_VII CD); 3.86- 3.96 (m, H-5 ^{XI ~ VXX} _C D); 3.87-3.92 (m, H-6 ^II_V1I CD); 3.83 (H-5 ^∑ CD); 3.75-3.83 (m, H-4 ^{XI "VXI} _C D); 3.76 (H-3 ^X _C D);

3.69-3.79 (m, H-3 ^{XI "VII} _CD ); 3.71 (H-4 ^X _C D); 3.65-3.73 (m,

_H _ ₆ , ^I I- ^V II _CD) . 3.64-3.66 (m, OCi? ₃ -6 _CD ); 3.55-3.57 (m,

0CH ₃ -3 _C D); 3.43 (H-2 ^I CD); 3.42-3.43 (m, 0Ctf ₃ -2 _CD ); 3.36-3.44 (m, H-2 ^{XI "VX: I:} CD); 3.05 (dd, IH, H-6 ^X _C D, WS ¹ = 5.5 Hz, ³ J ₆ ^I - ₆ ' ¹ = 14.2 Hz); 2.96 (dd, IH, H-6' ^X _C D, ³ Jg ' ^I -s ^I = 3.0 Hz, ³ Jg, ¹ _g ¹ = 14.2 Hz )

c) Preparation of 6 ^I -amidosuccinyl-6 ^{: ι:} -deoxy- per (2, 3, 6-tri-O-methyl) cyclomaltoheptaose, or compound

5a, of formula

5a In a clean and dry 100 ml flask, compound 4a (1.5 g, 1.08 mmol, 1 eq.) Is dissolved in 30 ml of anhydrous DMF under an inert atmosphere. The succinic anhydride (0.170 g, 1.7 mmol, 1.6 eq.) Dissolved in 8 ml of anhydrous DMF is added. The reaction medium is left under an inert atmosphere for 20 hours at room temperature. The reaction is stopped with 170 μL of water then the insolubles are filtered on paper. The filtrate is concentrated on a rotary evaporator then the residue is taken up in a minimum of water and lyophilized. Compound 5a is obtained with a yield of 76%.

TLC: R _f = 0.5 eluent: CHCl ₃ / MeOH 9/1 (v / v) Mp: 80 ° C (decomposition)

NMR ^X R CDC1 ₃ δ (ppm): 6.4 (t, 1H, NH-CD, ³ J _NH -H6 = 6 HZ); 5.25-5 (m, 7H, Hi-CD); 3.95-3.25 (m, H3-CD / H ₄ -CD / H ₅ - CD / H ₆ -CD / Hg _' -CD / 0CH ₃ -CD) 3.25-3.15 (m, H ₂ -CD); 2.75-2.4 (m, 4H, H / H _c )

10.2. Preparation of W-dodecyl-Jff _κ - (9-fluorenyl- methoxycarbonyl) -β-alanine, or compound 7c, of formula:

7c In a 100 mL flask, the N _α - (9-fluorenylmethoxycarbonyl) -L-β-alanine (commercial product) (2 g, 6.42 mmol, 1 eq.) Is dissolved in 12 mL of DMF, 3 mL (3 eq.) Of DIC then 1.93 g of hydrated HOBT (3 eq.) Dissolved in 7 ml of DMF are successively added. The reaction medium is kept under stirring for 2 hours. A solution of dodecylamine (1.75 g, 9.46 mmol, 1.5 eq.) In 40 ml of chloroform is then added and the reaction medium is left at room temperature 18 hours. The mixture is concentrated under vacuum taken up in DMF. After 3 hours in the refrigerator, the precipitate is filtered, washed with DMF and then dried with ether. The filtrate is collected and reprecipitated in the refrigerator. The precipitate obtained is filtered and dried with ether. Finally, the solid is dried under vacuum. Compound 7c is obtained with a yield of 47%. TLC: R _f = 0.8 eluent: CHCl ₃ / MeOH 95/5 (v / v) Mp: 143 ° C

^X R NMR (CDC1 _3, 500.13 MHz) δ (ppm): 7.78 (d, 2H, H ₄ / H ^{_4, 3} J _4-3 = ³ J _{4 '- 3'} = 7.5 Hz ); 7.60 (d, 2H, Hι / H, ³ Jι- ₂ = ³ Ji _' - _2' = 7.5 Hz); 7.35 (m, 4H, H ₂ / H ₂ - / H3 / H3; 5.55 (tl, 1H, NH); 5.52 (tl, 1H, NH); 4.36 (d, 2H, H _8, ³ Js = 2.8 Hz); 4.21 (t, IH, H _7, ³ J _7-8 = 2.8Hz); 3.5 (m, 2H, H _"); 3.23 ( q, 2H, H _lα ); 2.4 (t, 2H, Hβ, ³ J _α _ _β = 2.2 Hz) 1.6 (m, 2H, H _2α ); 1.4-1.1 (m , H _3α to H _llα ); 0.89 (t,

10.3. Preparation of compound 9d: In a 100 mL flask, compound 5a (780 mg, 0.51 mmol, 1 eq) is dissolved in 30 ml of DMF, 220 μL (2.75 eq) of DIC then 142 mg (2 , 75 eq) of HOBT dissolved in 2 ml of DMF are successively added. After 3.30 hours, compound 7c (160 mg, 0.62 mmol, ⁴ 1.2 eq.) Dissolved in 6 ml of chloroform is added. After 24 hours at room temperature, the reaction is stopped with 100 μL of water and the reaction medium is concentrated to dryness on a rotary evaporator. The crude product obtained is passed through a column of chromatography on silica gel (eluent gradient: CHCl ₃ / MeOH).

In the above examples, the thin layer chromatographies (TLC) were carried out on aluminum plates (5 × 7.5 cm) coated with silica gel 60 F ₂₅₄ (Merck). The compounds were revealed under UV light (λ = 254 nm), by spraying with an aqueous solution of H ₂ SO ₄ at 10% followed by a heating step for all the cyclodextrin derivatives, or by spraying a solution of ninhydrin at 0.2% in ethanol followed by a heating step for compounds having a primary amine function. The melting points were determined using a δfler bench requiring calibration with reference products from Merck Eurolab. The proton and carbon NMR experiments were recorded routinely at the frequency of 200.13 MHz and 50.32 MHz respectively on a Brucker AC 200 device equipped with a multi-core probe ( ¹ H, ¹³ C, ¹⁵ N, ³¹ P). The chemical shifts are given relative to an external reference, tetramethylsilane (δ = 0 ppm), and the internal calibrations were carried out using the residual solvent signal, with a possible correction for the water signal in temperature function. The deuterated solvents used (D ₂ 0, DMSO-c, CDC1 ₃ , Pyr-d ₅ ) came from Eurisotop. The measurements were made using a rigorous temperature control (+/- 0.1 K) at 298 K unless otherwise specified. The 90 ° dipstick values were ca. 10 μs for ^X H (0 dB attenuation), and ca. 20 μs for ¹³ C (2 dB attenuation). The one-dimensional spectra were acquired on 16 K points, and transformed on 32 K points (zero-filling). A possible correction of the baseline was made on the spectra. In order to facilitate the allocation of the signals, mono and two-dimensional spectra were carried out. They were recorded respectively at the frequency of 500.13 MHz and 125.77 MHz on a Brucker DRX 500 device equipped with a Broad Band Inverse probe

(bbi) 3 axes at 5 mm and acquired on 2048 points in F2 with 256 time increments in FI, the recycling time for each scan being approximately 1.5 seconds. The phased experiments were acquired in TPPI mode, and transformed into a matrix of IK x IK points (real-real matrix). The spectra were processed by a sine wave apodization function offset by π / 2 in the two dimensions, with a correction of the baseline. All spectra were processed using Mestrec or UXNMR (Brucker Analytische Messtechnik) software on the INDY (Silicon Graphics) workstation or on a PC. To facilitate the analysis of the spectra, the following abbreviations have been adopted: s, singlet, d, doublet, dd, doublet doublet, t, triplet, tl, wide triplet, q, quadruplet, and m, multiplet.

BIBLIOGRAPHY

[1] FR-A-2 792 942.

[2] Auzély-Velty et al. , Carbohydrate Research, 1999, 318, 82-90.

Claims

1. Cyclodextrin derivative corresponding to formula (I):

in which :

- R ¹ corresponds to formula (II)

-NH-E-AA- (L ¹ ) _p (L ² ) _q (II) in which: • E represents a hydrocarbon group, linear or branched, saturated or unsaturated, comprising from 1 to 15 carbon atoms and optionally comprising a or several heteroatoms, • AA represents the remainder of an amino acid, • L ¹ and L ² , identical or different, represent a hydrocarbon group, linear, branched and / or cyclic, saturated or unsaturated, comprising from 6 to 24 carbon atoms and optionally comprising one or more heteroatoms; • p and q, identical or different, are integers equal to 0 or 1, provided however that at least one of these integers is different from 0;

- R ² represents a hydrogen atom, a methyl group, an isopropyl group, a hydroxypropyl group or a sulfobutyl ether group; - R ³ represents a hydrogen atom or is identical to R ² except when R ² is a hydroxypropyl group;

All the R ⁴ represent either a hydroxyl group or R ² except when R ² is a hydroxypropyl group, or else one or more R ⁴ are identical to R ¹ and the other R ^{4 (s)} represent either a hydroxyl group, either R ² except when R ² is a hydroxypropyl group;

- n is an integer equal to 5, 6 or 7.

2. A derivative according to claim 1, in which, in formula (II), E corresponds to formula (III): -CO-XG ¹ -, in which X represents an alkylene group forming a bridge and comprising from 1 to 8 atoms carbon, while G ¹ represents a group -C0-, -NH- or -NR- in which R is a C1-C8 alkyl group.

3. A derivative according to claim 2, in which, in formula (III), X represents an alkylene group forming a bridge and comprising from 1 to 4 carbon atoms and, preferably, 2 carbon atoms.

4. Derivative according to any one of claims 1 to 3, in which, in formula (II), AA represents the remainder of an amino acid chosen from aspartic acid, glutamic acid, alanine, l arginine, asparagine, cysteine, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, tryptophan and valine.

5. A derivative according to claim 4, in which, in formula (II), AA represents the remainder of an amino acid chosen from aspartic acid, glutamic acid, isoleucine, leucine and phenylalanine, and , preferably, among aspartic acid and glutamic acid.

6. Derivative according to any one of the preceding claims, in which, in formula (II), AA represents the remainder of an amino acid belonging to the L series.

7. Derivative according to any one of the preceding claims, in which, in formula (II), L ¹ and L ² correspond to formula (IV): -G ² -Y, in which G ² represents a group -CO -, -NH- or -NR- where R is alkyl to C _s, while Y represents a linear alkyl chain C ₈ Cι ₈ or a cyclic lipophilic group or polycyclic.

8. A derivative according to claim 7, in which, in formula (IV), Y represents a C ₁₂ -C ₁₂ alkyl chain.

9. A derivative according to any one of the preceding claims, in which, in formula (II), E is linked by an amide bond to the residue AA, this residue itself being linked by an amide bond to the group (s) ( s) L ¹ and / or L ² .

10. Derivative according to one of the preceding claims, in which, in formula (II), E corresponds to the formula: -CO-X-CO- in which X has the same meaning as above, while L ¹ and L ² correspond to the formula: -NH-Y in which Y has the same meaning as above.

11. Derivative according to any one of the preceding claims, in which, in formula (I), R ¹ corresponds to the particular formula (VI):

in which: - X and Y have the same meaning as before; while - Z represents: either a covalent bond, in which case R ⁵ represents a hydrogen atom, a methyl group, the side chain of an amino acid or a group of formula: - (CH ₂ ) _t -CO-NH-Y in which t is 1 or 2 and Y has the same meaning as above, • or a hydrocarbon group forming a bridge, comprising from 1 to 4 carbon atoms and comprising one or more heteroatoms chosen from O and N, in which case R ⁵ represents a primary amino group or a group of formula: -NH-CO-Y in which Y has the same meaning as above.

12. The derivative according to claim 11, in which, in formula (VI):

- Z represents a covalent bond;

- Y is preferably a linear alkyl chain C ₈ Cι ₈ and more preferably in ₂ to Cι Cig; while

- R ⁵ represents a branched alkyl group with 4 carbon atoms, a benzyl group or a group of formula: - (CH ₂ ) t-CO-NH-Y, in which t is equal to 1 or 2 and Y represents, preferably, a linear alkyl chain C ₈ Cι ₈ and, more preferably, C _i2 Cι _6.

13. A derivative according to claim 11 or claim 12, in which, in formula (VI): - Z represents a covalent bond; - Y preferably represents a linear C ₈ to Cι ₈ and, better still, C ₁₂ to Cι ₆ alkyl chain; while

- R ⁵ represents a group of formula: - (CH _{2) t} -C0-NH-Y, wherein t is 1 or 2 and Y is preferably a linear alkyl chain C ₈ Cι ₈ and, better still, in Cι ₂ to Cι ₆ .

14. Derivative according to any one of the preceding claims, which comprises only one substituent R ¹ per molecule of derivative.

15. Derivative according to any one of the preceding claims, in which, in formula (I), n is equal to 6.

16. Derivative according to any one of the preceding claims, which is chosen from: ...

• N ', N "-didodecyl-.Z7ar- (6 ^I -amido-succinyl-6 ^x -deoxycyclomaltoheptaose) -L-aspartamide;

• 2v ^" ', iV" -didodecyl-N- (6 ^I -amido-succinyl-6 ^I -deoxycyclomaltoheptaose) -L-glutamide;

»IV ^r , N" -didodecyl-Nor- (6 ^I -amido-succinyl-6 ^I -deoxy- 2 ^x -0-methyl-hexakis (2 ^XX_VIX , 6 ^{IX "VII} -di-0-methyl) cyclo- maltoheptaose) -L-aspartamide; le ', N "-didodécyl-N _α - (6 ^x -amido-succinyl-6 ^x -deoxy- 2 ^x -0-methyl-hexakis (2 ^{IX" VIX} , 6 ^II_VII -di-0-methyl) cyclomaltoheptaose) - L-glutamide;

• TV '/ TV-didodecyl-Nα- (6 ^I -amido-succinyl-6 ^I -deoxy- 2 ^X , 3 ^x -di-0-methyl-hexakis (2 ^II_VI1 , 3 ^XI_VI1 , 6 ^{xx "VIX} -tri -0- methyl) cyclomaltoheptaose) -L-aspartamide; N '-dodecyl-iV'-hexadecyl-Nor (6 ^I -amidosuccinyl-6 ^I - deoxy-cyclomaltoheptaose) -L-aspartamide; N ', 77 "-didodecyl-N _α - (6 ^I -amido-succinyl-6 ^I -deoxy- 2 ^X , 3 ^x -di-0-methyl-hexakis (2 ^XI_VIX , 3 ^{XI" VXI} , 6 ^II_VII - tri-O-methyl) cyclomaltoheptaose) -L-glutamide; N ', W-dihexadecyl-ΛT _o r- (6 ^I -amidosuccinyl-6 ^I -deoxy- 2 ¹ , 3 -di-O-methyl-hexakis (2 ^J II-VII ^L , 3II-VII, / 6- I ^J I-VII ^r -tri-0- methyl) cyclomaltoheptaose) -L-aspartamide; and N'-dodecyl-Ttar- (6 ^I -amidosuccinyl-6 ^I -deoxy-2 ^I , 3 ^x -di- O-methyl-hexakis (2 ^II_VXI , 3 ^II_VI1 , 6 ^{IX "v: r: ι} -tri -0- methyl) cyclomaltoheptaose) -L-leucinamide.

17. A process for the preparation of a cyclodextrin derivative according to any one of claims 1 to 16, which comprises a step in which a cyclodextrin derivative of formula (VII) is reacted:

in which :

- E 'represents a hydrocarbon group, linear or branched, saturated or unsaturated, comprising from 1 to 15 carbon atoms, one or more heteroatoms and a free functional group capable of reacting with a hydroxyl, amino, carboxylic acid or thiol group of an amino acid to form a covalent bond; - R ² represents a hydrogen atom, a methyl group, an isopropyl group, a hydroxypropyl group or a sulfobutyl ether group;

- R ³ represents a hydrogen atom or is identical to R ² except when R ² is a hydroxypropyl group; - all R ⁴ represent either a hydroxyl group or R ² except when R ² is a hydroxypropyl group or one or more R ⁴ represent a group -NH-E 'and the other R or R ⁴ represent either a group hydroxyl, ie R ² except when R ² is a hydroxypropyl group;

- n is an integer equal to 5, 6 or 7;

with a compound of formula (VIII): -: \ AA '- (L ¹ ) _p (L ² ) _q (VIII)

in which :

• AA 'represents an amino acid comprising a hydroxyl, amino, carboxylic acid or free thiol group;

• L ¹ and L ² , identical or different, represent a hydrocarbon group, linear, branched and / or cyclic, saturated or unsaturated, comprising from 6 to 24 carbon atoms and optionally comprising one or more heteroatoms; • p and q, identical or different, are integers equal to 0 or 1, provided however that at least one of these integers is different from 0.

18. The method of claim 17, which further comprises a step consisting in reacting a monoamine derivative of cyclodextrin of formula (IX):

in which :

- R ² , R ³ and n have the same meaning as in formula (VII);

- all R ⁴ represent either a hydroxyl group or R ² except when R ² is a hydroxypropyl group, or one or more R ⁴ represent a group -NH ₂ and the other R or R ⁴ represent either a hydroxyl group , or R ² except when R ² is a hydroxypropyl group, with a precursor compound of group E 'comprising a free functional group capable of reacting with the amino group of the derivative of formula (IX), to obtain the cyclodextrin derivative of formula (VII).

19. The method of claim 17, which further comprises the steps of: reacting an amino acid, the functional group of which is intended to react with the free functional group of group E 'of the cyclodextrin derivative of formula (VII ) has been previously protected, with a precursor compound of group L ¹ and / or a precursor compound of group L ² , this precursor compound (s) comprising a free functional group capable of reacting with a hydroxyl group, amino, carboxylic acid or thiol of an amino acid to form a covalent bond; then - deprotect the protected functional group from the amino acid, to obtain the compound of formula (VIII).

20. The method of claim 18, wherein the group E 'precursor compound is an acid anhydride of formula (X):

in which X has the same meaning as above, which is reacted with the monoamine derivative of cyclodextrin of formula (IX) in an anhydrous medium and under an inert atmosphere.

21. Method according to any one of claims 17 to 20, in which the cyclodextrin derivative of formula (VII) and the compound of formula (VIII) are reacted in the presence of N, W'-diisopropylcarbodiimide (DIC) and hydroxybenzotriazole (HOBT).

22. Inclusion complex of a cyclodextrin derivative according to any one of claims

1 to 16, and a hydrophobic compound.

23. An inclusion complex according to claim 22, in which the hydrophobic compound is a medicinal active principle.

24. An inclusion complex according to claim 22, wherein the hydrophobic compound is a detergent for cell membranes.

25. An organized surfactant system comprising a cyclodextrin derivative according to any one of claims 1 to 16 or an inclusion complex according to any one of claims 22 to 24.

26. An organized surfactant system according to claim 25, wherein the surfactant is a phospholipid.