FR2854896A1 - New surfactants used for preparation of liposomes and cosmetic and/or dermatological compositions comprise polar saccharidal heads, spacer group and lipophilic residue - Google Patents

Abstract

New surfactants (I) comprise a polar saccharidal head, a spacer group comprising an ethylene glycol and/or propylene glycol polymer and a lipophilic residue. Surfactants of formula [Su-A ]n-X (I) are new. Su : a L-rhamnoside or L-fucoside group; A : a spacer group comprising a polymer of ethylene glycol and/or propylene glycol comprising 1-10 polyalkylene glycol residues, 1-10C amide, ester or polyhydroxyacid groups, 1-6C hydroxy groups or 1-6C carboxylic acid groups; n : 1-5; X : Lip comprising a lipophilic group comprising sterol, cannabinoid, retinoid, fatty acid, fat soluble vitamin or polyisoprenic hydrocarbon, or a group of formula (i), and at least one of R1-R6optionally aromatic 6-30C alkyl or cycloalkyl optionally including at least one ether, ester, amide, thioether, carbamate or thiocarbamate group and the others are H, and R1-R6 bond with Su-A. [Image] An independent claim is also included for cosmetic and/or dermatological compositions containing (I). ACTIVITY : Dermatological. No biological data is given. MECHANISM OF ACTION : None given.

Description

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 The present invention relates to novel surfactants with a saccharide polar head, liposomes prepared from these surfactants and cosmetic and / or dermatological compositions comprising them.

 In the field of skin care, we seek to provide skin cells with the elements (nutrients, active ingredients) that these cells need.

 In this regard, it is sought that the transfer of nutrients or active ingredient is done with the greatest possible efficiency, that is to say with the greatest possible specificity for the targeted cells, and with the greatest affinity possible for these same cells.

 In order to facilitate the penetration of active principles and / or nutrients into skin cells, the cosmetic and pharmaceutical industry has developed for many years particular formulations, such as liposomes, microemulsions, phase emulsions multi-lamellar solubilizers based on glycol ethers (transcutol).

 However, the effectiveness of the transfer of active ingredients to the skin cells by these formulations was limited and above all, these formulations were not specific for a given cell type, which further limited their effectiveness.

 Knowing the mechanism of action of certain active principles, we want to be able to convey them to their target cells so as to give their action a greater efficiency.

 This is particularly the case for skin epithelial cells, or keratinocytes, which it is desired to be able to target directly using specific formulations.

 For example, the Mannose-6phosphonate / cholesterylamine conjugate document is known to specify molecular adhesive linking cancer cells with vesicles. V. BARRAGAN, F. M. MENGER, K. L. CARAN, C.

VIDIL, A. MORERE and J. L. MONTERO, Chemical Communication, 1, 85-86, 2001, the use of certain particular surfactants in liposomes to target RM6P membrane receptors.

 However, it was not known to prepare liposome compositions for specific targeting of keratinocytes.

 For this purpose, the invention provides novel surfactants that can be incorporated into liposomal compositions that specifically target keratinocytes and transfer nutrients or active principles of these liposomes to the keratinocytes.

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O HO =-0\ L-rhamnoside HO OH et le H3C OH HO L-fucoside oh - A représente un bras espaceur sélectionné parmi les polymères d'éthylène glycol et/ou de propylène glycol comprenant de 1 à 10 résidus polyalkylène glycol, préférentiellement de 2 à 6 résidus polyalkylèneglycol ; A peut également représenter un groupement amide ou ester ou un polyhydroxyacide comprenant de 1 à 10 atomes de carbone, de 1 à 6 fonctions hydroxyle et de 1 à 6 fonctions acide carboxylique ;
Préférentiellement A représente un polymère d'éthylène glycol et/ou de propylèneglycol ; - n représente un entier allant de 1 à 5 ; - X représente un groupement choisi parmi * les composés désignés Lip choisis parmi les stérols, les cannabinoïdes, les rétinoïdes, les acides gras, les vitamines lipo-solubles et les hydrocarbures polyisopréniques ; * des molécules répondant à la formule (II) ci-dessous :

A first subject of the invention therefore consists of new surfactants defined by formula (I) below: [Su-A] nX (I) in which: - Su represents a group chosen from

And a H 3 OH OH L-fucoside oh-A represents a spacer arm selected from the ethylene glycol and / or propylene glycol polymers comprising from 1 to 10 polyalkylene glycol residues, preferentially from 2 to 6 polyalkylene glycol residues; A may also represent an amide or ester group or a polyhydroxy acid comprising from 1 to 10 carbon atoms, from 1 to 6 hydroxyl functions and from 1 to 6 carboxylic acid functions;
Preferably, A represents a polymer of ethylene glycol and / or of propylene glycol; n represents an integer ranging from 1 to 5; X represents a group chosen from the compounds designated Lip chosen from sterols, cannabinoids, retinoids, fatty acids, liposoluble vitamins and polyisoprenic hydrocarbons; molecules corresponding to formula (II) below:

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 wherein one or more of R, R2, R3, R4, R5 and R6 are a bond with a group Su-A-, and n is that number of bonds, one or more of R1, R2, R3, R4, R5 and R6, designated Y, are chosen from C6-C30 alkyls, linear, branched or cyclic, saturated or unsaturated, optionally aromatic, optionally comprising one or more functions ether, ester, amide, thio ether in the alkyl chain, several substituents R1, R2, R3, R4, R5 and R6 can be linked to form a single group, the other substituents R1, R2, R3, R4, R5 and R6 represent the hydrogen atom.

A first family of preferred surfactants object of the present invention consists of molecules corresponding to the formula (III) below:
Su-A-Lip (III) wherein Su, A and Lip have the same definition as above
Lip represents a lipophilic residue selected from sterols, cannabinoids, retinoids, fatty acids, fat-soluble vitamins and polyisoprenic hydrocarbons.

 Among the sterol type derivatives that may be used in the present invention, mention may be made of: cholesterol, animal and plant sterols, steroid hormones and bile acids.

 Among the cannabinoid-type derivatives that can be used in the present invention, mention may be made of: tetrahydrocannabinols, iso-tetrahydrocannabinols, brucéol, flémengine, rubranine.

Among the retinoid-type derivatives that may be used in the present invention, mention may be made of: retinol, retinoic acid, carotenoids
Among the fatty acids that can be used in the present invention, mention may be made of: palmitic acid, oleic acid, and all linear or branched, saturated or unsaturated, linear or branched C 1 -C 3 fatty acids with an even or odd number of carbons, functionalized or nonfunctionalized.

 Among the liposoluble vitamins that can be used in the present invention, mention may be made of: vitamins D, E, and K.

 Among the polyisoprenic hydrocarbons that may be used in the present invention, mention may be made of: terpene alcohols.

 The link between the spacer arm (A) and the lipophilic residue (Lip) is

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 advantageously by means of an ether, ester, amide, thioether, thioester, carbamate or ureido bond.

 Preferably, an ether linkage or an ester link is chosen.

dans laquelle un ou plusieurs des groupements R1, R2, R3, R4, R5 et R6 sont choisis parmi les groupements répondant à la formule Su-A- dans laquelle Su et A ont la même définition que ci-dessus, un ou plusieurs groupements RI, R2, R3, R4, R5 et R6 désignés Y sont choisis parmi les alkyles en C6-C30, linéaires, ramifiés ou cycliques, saturés ou insaturés, éventuellement aromatiques, comprenant éventuellement une ou plusieurs fonctions éther, ester, amide, thio éther, carbamate, thiocarbamate dans la chaîne alkyle, plusieurs substituants RI, R2, R3, R4, R5 et R6 pouvant être liés pour former un seul groupement ;
Les autres substituants RI, R2, R3, R4, R5 et R6 représentent l'atome d'hydrogène. A second family of surfactants which is preferably subject of the invention consists of the molecules corresponding to formula (II) below:

wherein one or more of R1, R2, R3, R4, R5 and R6 are selected from the groups of the formula Su-A- wherein Su and A have the same definition as above, one or more R1 groups. , R2, R3, R4, R5 and R6 designated Y are chosen from linear or branched or cyclic, saturated or unsaturated, optionally aromatic, C6-C30 alkyls, optionally comprising one or more ether, ester, amide or thio ether functions; carbamate, thiocarbamate in the alkyl chain, a plurality of substituents R1, R2, R3, R4, R5 and R6 being bondable to form a single group;
The other substituents R 1, R 2, R 3, R 4, R 5 and R 6 represent the hydrogen atom.

 The compounds of the invention are prepared by coupling methods well known to those skilled in the art and which are illustrated in the examples.

dérivés du résorcinol dans lesquels RI=R3=R5=H. Among the compounds of formula (II), the preferred

resorcinol derivatives in which R1 = R3 = R5 = H.

 R2, R4, R6 are chosen from the derivatives of formula Su-A- and the alkyls C6-C30 designated Y, at least one of R2, R4, R6 being a derivative of formula Su-A- as defined herein above and at least one of R2, R4, R6 being a group Y, C6-C30 alkyl as defined above.

 The preferred surfactants according to the present invention are those belonging to the list below:

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The invention also relates to liposomes comprising at least one compound of formula (I) as defined above.

 Liposomes are vesicles prepared from natural or synthetic amphiphilic compounds in aqueous solution. These amphiphilic compounds are organized into lamellar bilayers superimposed on each other by enclosing an aqueous space. The hydrophilic parts are oriented on either side of the bimolecular sheet and are always in contact with the aqueous medium. The hydrophobic portions of the amphiphilic molecules form the bimolecular sheet (Micelles, Monolayers and Biomembranes Malcom Jones N. and Dennis Chapman 1995, WileyLiss Inc.).

 By liposome is meant vesicles or lipid spherules, that is to say particles formed of a membrane consisting of one or more concentric layers, these sheets comprising one or more bimolecular layers of amphiphilic lipids encapsulating an aqueous phase. The aqueous phase may contain one or more water-soluble active agents and the bimolecular layers of amphiphilic lipids may contain one or more lipophilic active substances.

 These spherules generally have a mean diameter of between 10 nm5000 nm.

 The invention also relates to cosmetic and / or dermatological and / or pharmaceutical compositions comprising at least one compound of formula (I) as defined above in a cosmetologically and / or dermatologically and / or pharmaceutically acceptable carrier.

 The subject of the invention is also cosmetic compositions

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 and / or dermatological and / or pharmaceutical comprising lipid vesicles or spherules as defined above in a cosmetologically and / or dermatologically and / or pharmaceutically acceptable carrier.

 These compositions have the advantage of conveying nutrients and / or active ingredients specifically intended for keratinocytes to their target with an efficiency and specificity superior to those of the cosmetic and / or dermatological vehicles of the prior art.

 Among the active principles and nutrients that can be used in the present invention, mention may be made in particular of: vitamins, hormones, plasmids, anti-cancer compounds, anti-inflammatory compounds, cicatrizing agents, antibacterials, anti-fungal compounds , vaccines, antioxidants, sunscreens.

 In order to demonstrate the effectiveness of the surfactants of the invention for the recognition and targeting of keratinocytes when these surfactants are incorporated into liposomes, fluorescent labeling of these liposomes has been carried out.

 The encapsulation of fluorescent molecules in the liposomes makes it possible to highlight the phenomenon of recognition between the receptor present on the surface of the cell (lectin) and the labeled liposomes and to transfer the fluorescence into the target cells. This system is applied to the transfer of active ingredients.

 In more detail the problem that has been sought to solve is the specific targeting of the outer cells of the skin (the epidermis) and the introduction into these cells of an active ingredient.

 The aim of the invention is to target the epithelial cells of the skin, the keratinocytes. These cells have specific membrane receptors called lectins that are capable of recognizing an osidic entity.

 The recognition between keratinocytes and liposomes comprising the surfactants of the invention carrying a polar head of Lrhamnose or L-fucose type has been demonstrated. It has also been shown that an active ingredient (fluorescent molecules, drugs, cosmetics, flavors, fragrances, genes ...), encapsulated in these liposomes, can be transferred into keratinocytes and on the outer part of the skin (epidermis). .

EXPERIMENTAL PART
The surfactants, once synthesized, have been used for the preparation of large liposomes in which molecules are encapsulated

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 fluorescences and bioactive molecules. The interactions of these liposomes with living tissue and with keratinocyte cultures were then studied.

phosphocholine (POPC), le 2-oléoyl-1-palmitoyl-sn-glycéro-3-phospho-rac-(1- glycérol) (POPG) et le sel de triéthylammonium de la N-(fluorescéine-5- thiocarbamoyl)-1,2-dihexadécanoyl-sn-glycérol-3-phosphoéthanolamine (DHPEfluorecéine) provenant des Sociétés Sigma ou Avanti Polar Lipids (US) pour les deux premiers et d'Interchim pour le dernier. I / Preparation of liposomes
1 / Liposome preparation protocol
The lipids used are 2-oleoyl-1-palmitoyl-sn-glycero-3-

phosphocholine (POPC), 2-oleoyl-1-palmitoyl-sn-glycero-3-phospho-rac- (1-glycerol) (POPG) and the triethylammonium salt of N- (fluorescein-5-thiocarbamoyl) -1 2-dihexadecanoyl-sn-glycerol-3-phosphoethanolamine (DHPEfluorecéine) from Sigma or Avanti Polar Lipids (US) for the first two and Interchim for the latter.

We also used two amphiphilic glycosides whose structure is described in the diagram below.

Surfactants used for biological studies
The fluorescent molecule which is encapsulated in liposomes for experiments with keratinocyte cultures is propidium iodide (PI) used at a concentration of 1 μmolar in Phosphate Buffer Saline or PBS and from the Fluka Company.

 In a first step, the lipid films are prepared by mixing the desired amounts of the lipids dissolved in a chloroform / methanol mixture and then by evaporation of the solvent under reduced pressure. The POPC / POPG / surfactant molar ratios are 8 / 0.5 / 1.5 for a total lipid content of 5.10-7 moles and are used for experiments with cell cultures. The POPC / POPG / DHPE-fluorescein / surfactant molar ratios are 7.5 / 0.5 to 0.5 1.5 for a total lipid content of 5.10-7 moles and are used for skin sample experiments. The various operating conditions are combined in the table presented below. The film then obtained is left under high vacuum for one day in order to eliminate all traces of solvent.

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<Tb>
<Tb>

Type <SEP> lipids <SEP>% <SEP> molar <SEP> Medium
<tb><SEP> hydration experiments <SEP>
<tb> POPC <SEP> 80
<tb> Tests <SEP> with <SEP> the <SEP> POPC <SEP> PBS <SEP> + <SEP> iodide <SEP> of
<tb> cell cultures <SEP><SEP> POPG <SEP> 5 <SEP> propidium
<tb> Surfactant <SEP> 4 <SEP> or <SEP> 18 <SEP> 15
<tb> POPC <SEP> 75
<tb> Tests <SEP> on <SEP><SEP> POPG <SEP> 5 <SEP> PBS
<tb> samples <SEP> of <SEP> skin <SEP> DHPE-fluorescein <SEP> 5
<tb> Surfactant <SEP> 4 <SEP> or <SEP> 18 <SEP> 15
<Tb>

2 / Operating conditions for the preparation of large liposomes
In a second step, 0.5 ml of the 1 molar propidium iodide solution or 0.5 ml of the PBS solution are respectively added to the films which do not have DHPE-fluorescein or to the films containing this material. lipid. The aqueous mixture is then stirred for one hour at room temperature. Then, this mixture is extruded 19 times through a 100 nm pore-size polycarbonate membrane (LiposoFastTM Avestin (Canada)). The solution is then centrifuged at 15,000 rpm (Eppendorf Centrifuge 5804 R) for one hour to allow precipitation of the liposomes. The supernatant containing the unincorporated material (lipids and fluorescent molecules) is then removed and the liposomes are resuspended by adding an identical volume of PBS and centrifuged again. After two further washes with a solution of PBS, the liposomes are stored at 4 ° C. in a final volume of PBS of 30 l.

He / Biological tests
1 / Protocol of cultures of keratinocytes and preparations of the cuts of skin.

 The primary keratinocyte cultures are made from isolated children's foreskin cells and cultured in serum-free medium (SFM, Invitrogen) consisting of MCDB153 supplemented with epidermal growth factor (EGF, 5 ng / ml), a pituitary extract of b # uf (70 mg / ml), penicillin (1000 u / ml), streptomycin (100 u / ml) and amphotericin B (100 u / ml) (Invitrogen).

 The keratinocyte cultures are carried out in a 97 C incubator with a 5% CO 2 atmosphere and saturated with H 2 O. The maintenance cell is performed after seeding at 4000 cells / cm 2 in SFM medium. From

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 these cultures, the cells are trypsinized and seeded on glass slides at the density of 1000 cells / cm 2 and cultured for 2 to 3 days before incubation with liposomes.

 Skin biopsies are obtained from prepuce of children or abdominoplasties, frozen in a coating tissue (OCT, Miles) and stored at -80 C. The cuts of 6 m thick cutaneous biopsies are obtained by cryotomy then incubated in PBS / 0.1% gelatin for 2 hours at room temperature to allow blocking of nonspecific sites.

2 / Incubation Protocols
For incubation of the liposomes with the cell cultures in a four-well dish, 20 μl of the liposomal solution in PBS are added to the cells after removal of the culture medium.The incubation is maintained at 37 ° C. for 10 minutes. then after observation, the culture dish is incubated for an additional 30 minutes for a total of 40 minutes at 37 ° C. For each of these times, the follow-up of the incubation of the liposomes with the cells is visualized by means of a microscope Inverted Nikon Eclipse TE 300 with Hoffman contrast and epifluorescence The images are recorded using a Nikon Digital Still DXM 1200. The images are then visualized on screen with the ACT-application program. 1.

 For tests with skin sections, 10 l of liposomes are deposited on the slides placed in a box in a humid atmosphere and incubated for 2 hours in the dark. Then the slide is washed twice with PBS / 0.1% gelatin, then 1 time with PBS / 0.1% gelatin containing Hoescht dye to mark the nuclei and finally 1 time with PBS / 0.1% gelatin. The slides are then mounted on Mowiol and placed at 4 C to allow good drying. The visualization under the microscope is carried out after 24 hours. In parallel, a competition with free L-rhamnose, dissolved in isopropanol at a concentration of 5.10-5 mol / l, is carried out according to two protocols: a) the sections are preincubated with a solution of PBS / 0.1% gelatin + rhamnose for 2 hours and the liposomes are deposited as previously described; b) free L-rhamnose is added to the liposomal solution prior to its deposition on the sections. The experiments are then continued as described above.

 3 / Test results

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a / In vitro tests
For the tests carried out in vitro with the keratinocyte cultures, we observed the incorporation of the dye by the cells after their incubation with the liposomes carrying the surfactants of the invention.

7,,ex = 540-580 nm et demi = 600-660 nm pour révéler l'iodure de propidium. L'iodure de propidium, présent initialement au c#ur des liposomes, ne donne une coloration rouge que s'il pénètre soit directement dans les cellules mortes soit dans les cellules saines, en s'intercalant dans l'ADN, via une interaction avec les liposomes. Keratinocyte cultures are observed by visualization by Hoffman contrast microscopy and epifluorescence at wavelengths

7,, ex = 540-580 nm and half = 600-660 nm to reveal propidium iodide. Propidium iodide, initially present in the heart of liposomes, gives a red color only if it penetrates either directly into dead cells or into healthy cells, interposed in the DNA, via an interaction with liposomes.

 These visualizations are done after 10 minutes and 40 minutes of incubation.

FIGURES:
FIG. 1A1 represents a microscopy of keratinocytes incubated with liposomes containing surfactant 4 after 10 minutes of Hoffmann contrast acquisition incubation.

que la figure 1 A1 par acquisition en fluorescence (Aexc = 540-580 nm et Àemj = 600-660 nm). Figure 1A2 represents a microscopy of the same keratinocytes

as FIG. 1 A1 by fluorescence acquisition (Aexc = 540-580 nm and Aemj = 600-660 nm).

 FIG. 1B1 shows a microscopy of keratinocytes incubated with liposomes containing surfactant 18 after 10 minutes of Hoffmann contrast acquisition incubation.

que la figure IBI par acquisition en fluorescence (1,,, = 540-580 nm et demi = 600-660 nm). Figure 1B2 shows a microscopy of the same keratinocytes

that the IBI figure by fluorescence acquisition (1 ,,, = 540-580 nm and half = 600-660 nm).

 FIG. 2Ci shows a microscopy of keratinocytes incubated with liposomes containing surfactant 4 after 40 minutes of Hoffmann contrast acquisition incubation.

que la figure 1 Ci par acquisition en fluorescence (Aexc = 540-580 nm et Àemi = 600-660 nm). Figure 2C2 shows a microscopy of the same keratinocytes

that Figure 1 Ci by fluorescence acquisition (Aexc = 540-580 nm and Aemi = 600-660 nm).

 FIG. 2Di represents a microscopy of keratinocytes incubated with liposomes containing surfactant 18 after 40 minutes of Hoffmann contrast acquisition incubation.

que la figure ID, par acquisition en fluorescence (,,c = 540-580 nm et 1,,,i = 600-660 Figure 2D2 shows a microscopy of the same keratinocytes

that Figure ID, by fluorescence acquisition (,, c = 540-580 nm and 1 ,,, i = 600-660

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 nm).

These figures show a penetration of the fluorescent molecules into the keratinocytes. Since the passive passage of propidium iodide from the liposomes to the cells can not take place, the fluorescence emitted by the propidium iodide contained in the cells could only be observed thanks to the targeting of the liposomes on the keratinocytes and the internalization of their content by the cells. b / Ex vivo tests
For tests carried out ex vivo with the skin sections, we observed the tissue distribution of the liposomes in the epidermis or the upper layer and the stratum corneum of the epidermis after their incubation with the liposomes carrying the surfactants of the skin. 'invention.

FIGURES:
Figure 3Ai shows fluorescence microscopy of a section of skin incubated for 2 hours with liposomes containing surfactant 4 and with #exc = 330-380 nm and #emi> 420 nm.

18 et avec 7,X = 330-380 nm et Xemi > 420 nm. Figure 3A2 shows fluorescence microscopy of a section of skin incubated for 2 hours with liposomes containing the surfactant

18 and with 7, X = 330-380 nm and Xemi> 420 nm.

4 et avec ,eX = 465-495 nm et ,em; = 515-555 nm. Figure 3Bi shows fluorescence microscopy of a section of skin incubated for 2 hours with liposomes containing the surfactant

4 and with, eX = 465-495 nm and, em; = 515-555 nm.

 Figure 3B1 shows fluorescence microscopy of a section of skin incubated for 2 hours with liposomes containing surfactant 18 and with #exc = 465-495 nm and #emi = 515-555 nm.

liposomes contenant le tensioactif 4 et avec Àexc = 330-380 nm et 7,em; > 420 nm. FIG. 3A3 shows a fluorescence microscopy of a section of skin pre-incubated with free L-rhamnose and then incubated for 2 hours with the

liposomes containing surfactant 4 and with λex = 330-380 nm and 7, em; > 420 nm.

 Figure 3B3 shows the microscopy of a section of skin identical to that of Figure 3A3 but with #exc = 465-495 nm and #emi = 515-555 nm.

liposomes contenant le tensioactif 4 avec Xexc = 330-380 nm et 7,e",; > 420 nm. Figure 4A4 shows the fluorescence microscopy of a section of skin incubated for 2 hours with a mixture of free L-rhamnose and

liposomes containing surfactant 4 with Xexc = 330-380 nm and 7, e ",> 420 nm.

liposomes contenant le tensioactif 4 avec Àexc = 465-495 nm et demi = 515-555 nm. Figure 4B4 shows the fluorescence microscopy of a section of skin incubated for 2 hours with a mixture of free L-rhamnose and

liposomes containing surfactant 4 with λc = 465-495 nm and half = 515-555 nm.

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section de peau incubée sans le liposome avec Aexc = 330-380 nm et 1,,,,i > 420 nm. La figure 5B5 représente une microscopie de fluorescence d'une

section de peau incubée sans le liposome avec .ex = 465-495 nm et À.:mi = 515-555 nm. Figure 5As shows a fluorescence microscopy of a

section of skin incubated without the liposome with Aexc = 330-380 nm and 1 ,,,, i> 420 nm. Figure 5B5 shows a fluorescence microscopy of a

section of skin incubated without the liposome with .ex = 465-495 nm and AT: mi = 515-555 nm.

7v,exc = 330-380 nm et Aemi > 420 nm. FIG. 6A6 shows fluorescence microscopy of a section of skin incubated with liposomes containing no surfactant and with

7v, exc = 330-380 nm and Aemi> 420 nm.

 Figure 6B6 shows fluorescence microscopy of a skin section incubated with liposomes not containing surfactant and with xc = 465-495 nm and #emi = 515-555 nm.

 The skin sections were visualized in epifluorescence at two different wavelengths according to the fluorescent marker that we could observe. Indeed, the Hoescht 33258 dye, introduced during the washings, marks the nuclei by intercalating in the DNA of all the cells. It gives information to help discern the dermis of the epidermis. To visualize them, we subjected the sample to #exc 330-380 nm and we observed at #emi> 420 nm a blue color (Figures 3A1 and 3A2). On the other hand, the DHPEfluorescein, used for the preparation of liposomes, makes it possible to account for the tissue distribution of the liposomes on the skin sample that we submit at a wavelength #exc = 465-495 nm and we observe at #emi = 515-555 nm a green color (Figures 3Bi and 3B2).

 Preincubation of the skin samples with free L-rhamnose allowing the saturation of the specific sites, the addition of the liposomes makes it possible to note the displacement of the marking of the sites and to highlight the competition between the free sugar and the sugar constituting the head polar compounds of the invention.

 When the skin sections are pre-incubated for 2 hours with free lrhamnose and then incubated with the liposomes, an absence of fluorescence of the epidermis and the stratum corneum has been observed (FIGS. 3A3 and 3B3).

 For the skin section incubated simultaneously with the free L-rhamnose and the liposomal solution, a strong fluorescence is observed at the level of the upper part of the epidermis and the stratum corneum (FIGS. 4A4 and 4B4).

 On skin sections incubated either without liposomes (FIGS. 5A and 5B5) or with control liposomes not containing the surfactant (FIGS. 6A6 and 6B6), no fluorescence was observed.

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c / Conclusion of test results
The biological tests carried out with the invention indicate that it fully fulfilled the purpose that was sought. Indeed, the various results show that an interaction occurred between the liposomes carrying the compounds of the invention and the keratinocytes which were the target cells. And the active ingredient (fluorescent probe) has been selectively incorporated within the target cells.

III / Summary
Thin layer chromatography (TLC) was performed on Merck 60 F354 aluminum silica plate (article 5554). Depending on their nature, the products were revealed either in the UV light (254nm) for the compounds having a chromophore, or with anisaldehyde solution and then heating for the glycosylated and sterol-type compounds, or with a solution of vanillin and then heating for retinoid or cannabinoid compounds.

 Purification of the compounds by chromatography was carried out either on silica gel with Carlo Erba silica (Silica Gel 60Â, particle size: 35-70 m) or on Florisil Fluka gel (100-200 mesh).

 The uncorrected melting points were determined in capillary on a Büchi 530 apparatus.

 The rotational powers were determined using a Perkin-Elmer 241 polarimeter set on the sodium D line.

 The mass spectra were recorded either on a Jeol JMS-DX300 apparatus by the positive FAB ionization method with 3-nitrobenzyl alcohol (NOBA) used as a template, or on a Waters 2615 micromass / zq apparatus by the method. Electro-Spray in positive mode (ESI +) and / or in negative mode (ESI-).

 The proton NMR spectra were recorded at room temperature on a Brüker DPX 200 (at a frequency of 200MHz) or Brüker DRX 400 (at a frequency of 400MHz). The chemical shifts (8) are expressed in ppm relative to the signal of CHCl3 fixed at 7.24ppm or methanol fixed at 3.30ppm taken as internal reference. The multiplicity of signals is indicated by one (or more) lowercase letter (s): (s) singlet, (d) doublet, (t) triplet, (q) quadruplet, (qt) quintet, (m) massive or multiplet. The coupling constants (J) are expressed in Hertz.

 The carbon 13 NMR spectra were recorded either on a Brüker DRX 400 (at a frequency of 100.6 MHz) or on a Brüker 200 (at a frequency of 50.32 MHz). The chemical shifts (#) are expressed in ppm relative to the tetramethylsilane signal taken as internal reference.

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 The solvents used were distilled and rendered anhydrous before use according to the procedures reported by Perrin, D.D .; W. L. Purification of Laboratory Chemicals, 3rd Ed., Pergamon Press, 1988.

 The different commercial reagents used come from Aldrich, Fluka or Avocado companies.

 The numbering used for the description of the surfactants and for the different lipophilic parts is given directly on the molecules. For the description of the amphiphilic glycosides, the polar part is always numbered first and the ethylene glycol part is not numbered.

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A / Synthesis of 4,5 and 8 Amphiphilic Glycosides with Cholesterol as Lipophilic Part

p-toluènesulfonate de choles-5-en-3p-ol 1
Une solution de cholest-5-en-3p-ol (5 g, 12,9 mmoles) et de chlorure de p-toluènesulfonyle (2,7 g, 14,2 mmoles) dans de la pyridine (12 ml) est agitée pendant 12 heures. Après addition d'eau, le mélange est extrait avec de l'éther éthylique. Les phases organiques réunies sont lavées avec de l'eau, séchées sur du sulfate de sodium anhydre et enfin concentrées sous vide. Le résidu obtenu est précipité dans un mélange dichlorométhane / méthanol pour conduire au p-

toluènesulfonate de cholest-5-èn-3(3-0l 1 qui est recristallisé dans de l'éther de pétrole et obtenu sous forme de cristaux blancs (Rdt=90%).
Rf 0,80 (CH2C12)
Pf 130-132 C

RMN IH (ceci3,250 MHz) # (ppm) : 7,82 (2H, d, Jo-H-m-H=8,3 Hz, o-H-Ar) ; (2H, d, Jm-H-o-H=8,6 Hz, m-H-Ar) ; 5,32(1H, d, J6-7=5,3 Hz, H-6) ; 4,29-4,40(1H, m, H-3) ; 1,62 (3H, s, H-CH3-Ar) ; 0,99 (3H, s, H-19) ; 0,92 (3H, d, J2i-2o=7,5 Hz ; H-21) ; 0,89 (6H, d, J26-25=6,6 Hz, H-26, H-27) ; 0,68 (3H, s, H-18).

p-toluenesulfonate of choles-5-en-3p-ol 1
A solution of cholest-5-en-3p-ol (5 g, 12.9 mmol) and p-toluenesulfonyl chloride (2.7 g, 14.2 mmol) in pyridine (12 ml) is stirred for 12 hours. After addition of water, the mixture is extracted with ethyl ether. The combined organic phases are washed with water, dried over anhydrous sodium sulfate and finally concentrated under vacuum. The residue obtained is precipitated in a dichloromethane / methanol mixture to give the p-

cholest-5-en-3-toluenesulfonate (3-011) which is recrystallized from petroleum ether and obtained in the form of white crystals (yield = 90%).
Rf 0.80 (CH2Cl2)
Mp 130-132 ° C

1 H NMR (this3,250 MHz) # (ppm): 7.82 (2H, d, Jo-HmH = 8.3 Hz, oH-Ar); (2H, d, Jm-HoH = 8.6 Hz, mH-Ar); 5.32 (1H, d, J6-7 = 5.3 Hz, H-6); 4.29-4.40 (1H, m, H-3); 1.62 (3H, s, H-CH3-Ar); 0.99 (3H, s, H-19); 0.92 (3H, d, J 21 -20 = 7.5 Hz, H-21); 0.89 (6H, d, J26-25 = 6.6 Hz, H-26, H-27); 0.68 (3H, s, H-18).

13C NMR SCDCl3, 50MHz) # (ppm): 44.4 (C-5); 138.9 (o-C-Ar); 134.8 (o-C-Ar); 129.7 (m-C-Ar); 127.6 (m-C-Ar); 123.5 (C-6); 82.3 (C-3); 56.6 (C-14); 56.1 (C-17); 49.9 (C-9); 42.3 (C-13); 39.7 (C-16); 39.5 (C-24); 38.9 (C-4); 36.9 (C-1); 36.3 (C-10); 36.2 (C-22); 35.8 (C-20); 31.9 (C-7); 31.8 (C-8); 27.7 (C-12); 28.2 (C-2); 28 (C-25); 24.2 (C-15); 23.8 (C-23); 22.8 (C-27); 22.6 (C-26); 21.6 (C-11); 21 (CCH3-Ar); 19.2 (C-19); 18.7 (C-21), 11.8 (C-18).

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 MS (FAB + / NOBA) m / z: 369 [M-tosyl + H] +.

Une solution de p-toluènesulfonate de choles-5-èn-3(3-0l 1 (1 mmole) et de tri(éthylèneglycol) ou d'hexa (éthylèneglycol) mmoles) dans du dioxane anhydre (20 ml) est portée à reflux pendant 5 heures. Après addition d'eau, la solution est extraite avec de l'acétate d'éthyle puis la phase organique est lavée avec une solution aqueuse d'hydrogénocarbonate de sodium à 5% puis avec de l'eau. Elle est ensuite séchée sur du sulfate de sodium anhydre et concentrée sous pression réduite. Le résidu obtenu est à chaque fois purifié par chromatographie sur colonne de gel de silice. Les conditions d'élution et le rendement de chaque composé sont donnés ciaprès.

General procedure for synthesis of the cholesterol spacer moiety

A solution of p-toluenesulfonate of choles-5-en-3 (3-011 (1 mmol) and tri (ethylene glycol) or hexa (ethylene glycol) mmol) in anhydrous dioxane (20 ml) is refluxed. for 5 hours. After addition of water, the solution is extracted with ethyl acetate and then the organic phase is washed with a 5% aqueous solution of sodium hydrogencarbonate and then with water. It is then dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue obtained is each time purified by column chromatography on silica gel. The elution conditions and the yield of each compound are given below.

8- (cholest-5-en-3p-yloxy) -3,6-dioxaoctan-1-ol 2 Elution with a gradient of ethyl acetate (2-8%) in petroleum ether leads to 8- (cholest-5-en-33-yloxy) -3,6-dioxaoctan-1-ol 2 in the form of a white paste (yield = 78%).

 Rf 0.17 (EP / AcOEt 6/4).

8 (ppnri : 5,34 (1H, d, J6-7=5,2 Hz, H-6) ; 3,73-3,59 (12H, m, H-CH20) ; 3,21-3,17 (1H, m, H-3) ; 2,79(1H, m, OH) ; 1,02 (3H, s, H-19) ; 0,91 (3H,

d, J2,-2o=6,5 Hz ; H-21) ; 0,87 (6H, d, J26-25=6,6 Hz, H-26, H-27) ; 0,68 (3H, s, H-18). 1H NMR (CDCl3, 250 MHz)

8 (ppn: 5.34 (1H, d, J6-7 = 5.2 Hz, H-6); 3.73-3.59 (12H, m, H-CH2O); 3.21-3.17 (1H, m, H-3); 2.79 (1H, m, OH); 1.02 (3H, s, H-19); 0.91 (3H,

d, J2, -2o = 6.5 Hz; H-21); 0.87 (6H, d, J26-25 = 6.6 Hz, H-26, H-27); 0.68 (3H, s, H-18).

 13 C NMR (CDCl 3, 50 MHz) δ (ppm): 141.3 (C-5); 122 (C-6); 80 (C-3); 73-67.5 (5 * CCH2O); 62.2 (C-CH 2 OH); 57.2 (C-14); 56.6 (C-17); 50 (C-9); 42.7 (C-13); 40.2 (C-16); 39.9 (C-24); 39.4 (C-4); 37.6 (C-1); 37.3 (C-10); 36.6 (C-22); 36.2 (C-20); 32.3 (C-7, C-8); 28.7 (C-2, C-12); 28.4 (C-25), 24.7 (C-15); 24.3 (C-23); 23.2 (C-27); 23 (C-26); 21.5 (C-11); 19.8 (C-19); 19.1 (C-21); 12.3 (C-18).

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MS (FAB + / NOBA) m / z: 541 [M + Na] +; 369 [M-TEG + H] +.

17- (cholest-5-en-3-yloxy) -3,6,9,12,15-pentaoxaheptadecan-1-ol 3 Elution with a gradient of ethyl acetate (2-8%) in the petroleum ether gives 1 7- (cholest-5-en-3 (3-yloxy) -3,6,9,12,15-pentaoxaheptadecan-1-ol 3 in the form of a white paste (yield = 67%). ).

 Rf 0.12 (EP / AcOEt 6/4).

d, J21-20=6,4 Hz ; H-21) ; 0 84 (6H, d, J26-25=6,6 Hz, H-26, H-27) ; 0,65 (3H, s, H-18). NMR (CDC13.200 MHz) # (ppm): 5.32 (1H, d, J6-7 = 4.8 Hz, H-6); 3.73-3.58 (24H, m, H-CH 2 O); 3.22-3.10 (1H, m, H-3); 2.86 (1H, m, OH); (3H, s, H-19); 0.89 (3H,

d, J21-20 = 6.4 Hz; H-21); 84 (6H, d, J26-25 = 6.6 Hz, H-26, H-27); 0.65 (3H, s, H-18).

22,7 (C-27); 22,5 (C-26) ; 21 (C-ll); 19,2 (C-19); 18,6 (C-21); 11,7 (C-18). 13C NMR (CDCl3, 50MHz) # (ppm): 140.6 (C-5); 121.3 (C-6); 79.3 (C-3); 72.6-67.1 (11 ° C-CH 2 O); 61.3 (C-CH 2 OH); 56.6 (C-14); 56 (C-17); 50 (C-9); 42.1 (C-13); 39.7 (C-16); 39.4 (C-24); 38.9 (C-4); 37.1 (C-1); 36.7 (C-10); 36.1 (C-22); 35.7 (C-20); 31.7 (C-7, C8); 28.2 (C-2, Cl 2); 27.8 (C-25); 24.1 (Cl 5); 23.8 (C-23);

22.7 (C-27); 22.5 (C-26); 21 (C-11); 19.2 (C-19); 18.6 (C-21); 11.7 (C-18).

 MS (FAB + / NOBA) m / z: 689 [M + K] +; 673 [M + Na] +; 651 [M + H] +; 369 [MTEG + H] +.

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a-L-rhamnopyranoside de 8-(cholest-5-èn-3p-yloxy)-3,6-dioxaoctanyle 4
A une solution de L-(+)-rhamnose (61 mg, 0.33 mmole) et du composé 2 (85 mg, 0.17 mmole) dans du tétrahydrofurane (4 ml) est additionné de l'acide p-toluènesulfonique (72,4 mg, 0.38mmole). Le mélange réactionnel est laissé sous agitation à 60 C pendant 3 jours. Après addition de carbonate de sodium anhydre en poudre, le mélange est filtré sur célite et le filtrat concentré sous pression réduite. Synthesis of amphiphilic glycosides 4,5 and 8

α-Rhamnopyranoside of 8- (cholest-5-en-3β-yloxy) -3,6-dioxaoctanyl 4
To a solution of L - (+) - rhamnose (61 mg, 0.33 mmol) and Compound 2 (85 mg, 0.17 mmol) in tetrahydrofuran (4 ml) was added p-toluenesulfonic acid (72.4 mg). 0.38mmol). The reaction mixture is stirred at 60 ° C. for 3 days. After adding anhydrous sodium carbonate to powder, the mixture is filtered on celite and the filtrate concentrated under reduced pressure.

The crude residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (1-5%) in dichloromethane] to give surfactant 4 in the form of a tacky white foam (yield = 30%).

Rf 0.47 (CH 2 Cl 2 / MeOH 9/1).

[?] D -33.3 (c = 1, CHCl3).

ô (ppm) : 5,36 (1H, d, J6'-7,=5,1 Hz, H-6') ; 4,87 (1H, d, J1-2=1,3 Hz, H-1) ; 3,99 (1H, m, H-2) ; 3,84-3,64 (14H, m, H-CH20, H-3, H-5) ; 3,46 (1H, m, H-4) ; 3,24-2,95 (2H, m, H-3', OH) ; 1,34 (3H, d, J6-5=6,2 Hz, H-6) ;

1,02 (3H, s, H-19') ; 0,93 (3H, d, J2r-20-=6,5 Hz, H-21') ; 0 89 (6H, d, J26'-25,=6,5 Hz, H-26', H-27') ; 0 69 (3H, s, H-18'). 1 H NMR (CDCl 3, 250 MHz)

δ (ppm): 5.36 (1H, d, J6-7, = 5.1 Hz, H-6 '); 4.87 (1H, d, J1-2 = 1.3 Hz, H-1); 3.99 (1H, m, H-2); 3.84-3.64 (14H, m, H-CH 2 O, H-3, H-5); 3.46 (1H, m, H-4); 3.24-2.95 (2H, m, H-3 ', OH); 1.34 (3H, d, J6-5 = 6.2 Hz, H-6);

1.02 (3H, s, H-19 '); 0.93 (3H, d, J2r-20- = 6.5 Hz, H-21 '); 0 89 (6H, d, J26'-25, = 6.5 Hz, H-26 ', H-27'); 0 69 (3H, s, H-18 ').

 13C NMR (CDCl3, 100MHz) # (ppm): 141.2 (C-5 '); 122 (C-6 '); 100.3 (C-1); 80 (C-3 '); 73.5 (C-4); 72.1 (C-3); 71.1 (C-CH 2 O); 71.1 (C-2); 71 (C-CH 2 O); 70.7 (C-CH 2 O); 68.7 (C-5); 67.6 (C-CH 2 O); 66.9 (C-CH 2 O); 57.2 (C-14 '); 56.6 (C-17 '); 50.6 (C-9 '); 42.7 (C-13 '); 40.2 (C-16 '); 39.9 (C-24 '); 39.4 (C-4 '); 37.3 (C-10 '); 36.6 (C-22 '); 36.2 (C-20 '); 32.4 (C-7 '); 32.3 (C-8 '); 28.7 (C-2 '); 28.6 (C-12 '); 28.4 (C-25 '); 4.7 (C-15 '); 24.3 (C-23 '); 23.2 (C-27 '); 23 (C-26 '); 21.5 (C-11 '); 19.8 (C-19 '); 19.1 (C-21 '); 18.0 (C-6); 12.3 (C-18 ').

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MS (FAB + / NOBA) m / z: 687 [M + Na] +; 665 [M + H] +.

L-fucopyranoside of 8- (cholest-5-en-3β-yloxy) -3,6-dioxaoctanyl
To a solution of L - (+) - fucose (200 mg, 1.22 mmol) and compound 2 (1.3 g, 366 mmol) in tetrahydrofuran (4 ml) was added p-toluenesulfonic acid. (419 mg, 2.44 mmol). The reaction mixture is stirred at 55 ° C. for 1 day. After adding anhydrous sodium carbonate to powder, the mixture is filtered on celite and the filtrate concentrated under reduced pressure. The crude residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (1-5%) in dichloromethane] to give the surfactant 5 in the form of a sticky white foam (Yield = 40%, anomers [alpha] / ss 77/23).

 Rf 0.41 (CH 2 Cl 2 / MeOH 95/5).

[?] D29.5 (c = 1.01, CHCl3).

J6-5=6,6Hz, H-6 anomère a) ; 0,99 (3H, s, H-19') ; 0,91 (3H, d, J2r.20'=6,4Hz; H-21') ; 0,86 (6H, d, J26-.25'=6,6Hz, H-26', H-27') ; 0,67 (3H, s, H-18'). TH NMR (CD Ch = 200 MHz) δ (ppm): 5.34 (1H, d, J6 = 4.4Hz, H-6 '); 4.9 (1H, d, JI-2 = 3.3Hz, H1 anomeric a); 4.27 (1H, d, JI-2 = 6.6 Hz, H-1 anomeric ss); 4.06- 3.59 (16H, m, H-2, H-3, H-4, H-5, H-CH 2 O); 3.24-3.11 (1H, m, H-3 '); 2.66 (1H, m, OH); (3H, d, J6-5 = 6.4Hz, H-6 anomeric ss); 1.29 (3H, d,

J6-5 = 6.6 Hz, H-6 anomer a); 0.99 (3H, s, H-19 '); 0.91 (3H, d, J20.20 '= 6.4Hz, H-21'); 0.86 (6H, d, J 26 -25 '= 6.6 Hz, H-26', H-27 '); 0.67 (3H, s, H-18 ').

13 C NMR (CDCl 3, 100MHz) δ (ppm): 141.3 (C-5 '); 122.1 (C-6 '); 103.6 (C-1 p-anomer); 99.5 (C-1 anomer a); (C-3 '); 72.1 (C-4); 71.5 (C-3); 71.2, 70.9, 70.6 (4 * C-CH 2 O); 69.7 (C-2); 67.7 (C-CH 2 O); 67.6 (C-CH 2 O); 66.5 (C-5); 57.2 (C-14 '); 56.5 (C-17 '); 50.6 (C-9 '); 42.7 (C-13 '); 40.2 (C-16 '); 39.9 (C-24 '); 39.3 (C-4 '); 37.6 (C-1 '); 37.3 (C-10 '); 36.6 (C-22 '); 36.2 (C-20 '); 32.4 (C-7 '); 32.3 (C-8 '); 28.7 (C-2 '); 28.6 (C-12 '); 28.4 (C-25 '); 24.7 (C-15 '); 24.2

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SM (ESI+ /30e V) m/z : 687 [M+Na]+.

(C-23 '); 23.2 (C-27 '); 23 (C-26 '); 21.5 (C-1 1); 19.8 (C-19 '); 19.1 (C-21 '); 16.8 (C-6 P-anomer); 16.7 (C-6 anomeric a); 12.3 (C-18 ').

MS (ESI + / 30th V) m / z: 687 [M + Na] +.

1,2,3,4-tétra-O-acétyl-L-rhamnopyranoside 6
Du L-(+)-rhamnose (5g, 27,4 mmoles) est dissous dans de la pyridine (21 ml). De l'anhydride acétique (42 ml) est alors additionné goutte à goutte et le mélange réactionnel est laissé sous agitation à température ambiante pendant une nuit. Celui-ci est alors repris par de l'acétate d'éthyle et lavé 6 fois avec une solution aqueuse saturée de sulfate de cuivre puis avec de l'eau. Les phases organiques sont alors séchées sur du sulfate de sodium anhydre et concentrées sous pression réduite.

1,2,3,4-tetra-O-acetyl-L-rhamnopyranoside 6
L - (+) - rhamnose (5g, 27.4 mmol) is dissolved in pyridine (21 ml). Acetic anhydride (42 ml) is then added dropwise and the reaction mixture is stirred at room temperature overnight. This is then taken up in ethyl acetate and washed 6 times with a saturated aqueous solution of copper sulfate and then with water. The organic phases are then dried over anhydrous sodium sulphate and concentrated under reduced pressure.

The residue obtained is chromatographed on a column of silica gel [eluent: dichloromethane] to give compound 6 in the form of a colorless gum (Yield = 96%, anomers [alpha] / ss 70/30).

 Rf 0.53 (EP / Et20 3/7).

 [a] D 43.6 (c = 1.01, CHCl3).

anomère a : 8 (ppm) : 6,02 (1H, d, JI-2=1,8Hz; H-1) ; 5,3 (1H, dd, J3-4=9,9Hz, J3-2=3,5Hz, H-3) ; 5,24 (1H, dd, J2-3=3,5Hz, J2-i=l,9Hz, H-2) ; 5,11(1H, dd, J4-5=9,7Hz, J4-3=9,9Hz, H-4) ; 3,93 (1H, dd, J5-4=9,7Hz, J5-6=6,2Hz, H-5)

; 2,22-2,19 (12H, s, H-COCH3) ; 1,23 (3H, d, J6-5=6,2Hz, H-6). anomère (3 : S (ppm) : 5,84 (1H, d, JI-2=1 2Hz; H-1) ; 5,3 (1H, dd, J3.4=9,9Hz, J3-2=3,5Hz, H-3) ; 5,24 (1H, dd, J2-3=3,5Hz, J2-i=l,2Hz, H-2) ; 5,11( 1 H, dd, J4-5=9,7Hz, J4-3=9,9Hz, H-4) ; 3,93 ( 1 H, dd, J5-4=9,7Hz, J5-6=6,2Hz, H-5)

; 2,22-2,19 (12H, s, H-COCHI) ; 1,28 (3H, d, J6-5=6,2Hz, H-6). 1H NMR (CDCl3, 250MHz)

anomer a: 8 (ppm): 6.02 (1H, d, JI-2 = 1.8 Hz, H-1); 5.3 (1H, dd, J3-4 = 9.9Hz, J3-2 = 3.5Hz, H-3); 5.24 (1H, dd, J2-3 = 3.5Hz, J2-i = 1.9Hz, H-2); 5.11 (1H, dd, J4-5 = 9.7 Hz, J4-3 = 9.9Hz, H-4); 3.93 (1H, dd, J5-4 = 9.7 Hz, J5-6 = 6.2 Hz, H-5)

; 2.22-2.19 (12H, s, H-COCH3); 1.23 (3H, d, J6-5 = 6.2 Hz, H-6). anomeric (3: S (ppm): 5.84 (1H, d, JI-2 = 12Hz, H-1); 5.3 (1H, dd, J3.4 = 9.9Hz, J3-2 = 3 , 5Hz, H-3); 5.24 (1H, dd, J2-3 = 3.5Hz, J2-i = 1.2Hz, H-2); 5.11 (1H, dd, J4-5 = 9.7 Hz, J4-3 = 9.9Hz, H-4) 3.93 (1H, dd, J5-4 = 9.7Hz, J5-6 = 6.2Hz, H-5)

; 2.22-2.19 (12H, s, H-COCHI); 1.28 (3H, d, J6-5 = 6.2 Hz, H-6).

 13 C NMR (CDCl 3, 50MHz) δ (ppm): 170.2, 169.9, 169.8, 169.7 (6 ° C-COCH 3); 168.4 (C-COCH3 on C-1 anomeric ss); 168.3 (C-COCH3 on C-1 anomer a); 90.5 (C-1 anomer a); 90.2 (C-1 anomer a); 71.3, 70.6, 70.4, 70, 68.7, 68.6, 68.5, 68.4 (C-2 a,

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(3, C-3 a,(3, C-4 a,(3, C-5 a,/3); 20,8, 20,7, 20,6, 20,5 (8*C-COÇH3); 17,3 (C-6 anomère a); 17,2 (C-6 anomère P).

(3, C-3a, (3, C-4a, (3, C-5a, / 3), 20.8, 20.7, 20.6, 20.5 (8 * C-CHCH3) 17.3 (C-6 anomer a); 17.2 (C-6 P-anomer).

MS (ESI + / 30eV) m / z: 371 [M + K] +; 355 [M + Na] +; 296 [M-OAc + Na] +.

2,3,4-tri-O-acetyl-α-rhamnopyranoside of 17- (cholest-5-en-3-yloxy) -
3,6,9,12,15-pentaoxaheptadecyl 7
To a solution of 1,2,3,4-tetra-O-acetyl-L-rhamnopyranoside 6 (96 mg, 0.29 mmol) and 17- (cholest-5-en-3β-yloxy) -3,6,9 12.15-pentaoxaheptadecan-1-ol (245 mg, 0.38 mmol) dissolved in anhydrous dichloromethane (2 ml) is added dropwise boron trifluoride etherate (0.3 ml, 1.94 mmol). The reaction mixture is stirred at room temperature for 3 hours. It is then washed with a saturated aqueous solution of sodium hydrogencarbonate and then with water. The organic phase is dried over anhydrous sodium sulphate and then concentrated in vacuo. The residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (0-5%) in dichloromethane] to yield the acetylated surfactant 7 in the form of a colorless oil (Yield = 25%).

Rf 0.58 (CH 2 Cl 2 / MeOH 9/1). [[alpha]] D 40.6 (c = 1, CHCl3).

J2r-2o-=6,6Hz; H-21') ; 0,85 (6H, d, Jzb-2s=6,6Hz, H-26', H-27') ; 0,66 (3H, s, H-18'). RMN 13C (CDCl3, 50MHz) 1H NMR (CDCl3, 200MHz) δ (ppm): 5.29-5.23 (3H, m, H-2, H-3, H-6 '); 5.04 (1H, dd, J4-5 = 9.8Hz, J4-3 = 9.8Hz, H-4); 4.76 (1H, s, H1); 3.91 (1H, dd, Js = 9.9Hz, Js-6 = 6.1Hz, H-5); 3.84-3.51 (24H, m, H-CH 2 O); 3.22-3.11 (1H, m, H-3 '); (9H, s, H-COCH3); 1.2 (3H, d, J6-5 = 6.4Hz, H-6); 0.98 (3H, s, H-19 '); 0.9 (3H, d,

J2R-2O- = 6.6Hz; H-21 '); 0.85 (6H, d, Jzb-2s = 6.6 Hz, H-26 ', H-27'); 0.66 (3H, s, H-18 '). 13C NMR (CDCl3, 50MHz)

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(C-26') ; 21,1 (C-11') ; 20,8, 20,7, 20,6 (3*C-COCH3) ; 19,3 (C-19') ; 18,7 (C-21') ; 17,4 (C-6) ; 11,8 (C-18'). # (ppm): 170.169.9, 169.8 (3 ° C-COCH3); 141 (C-5 '); 121.5 (C-6 '); 97.6 (C-1); 79.5 (C-3 '); 71.2 (C-4); 70.9 (C-3); 70.8 (C-2); 70.6, 70.5, 70.1, 69.9 (4 ° C-CH 2 O); 69.2 (C-5); 67.3.67, 66.3 (3 ° C-CH 2 O); 56.8 (C-14 '); 56.2 (C-17 '); 50.2 (C-9 '); 42.3 (C-13 '); 39.8 (C-16 '); 39.5 (C-24 '); 39 (C-4 '); 37.3 (C-1 '); 36.9 (C-10 '); 36.2 (C-22 '); 35.8 (C-20 '); 32 (C-7 '); 31.9 (C-8 '); 28.4 (C-2 '); 28.2 (C-12 '); 28 (C-25 '); 24.3 (C-15 '); 23.8 (C-23 '); 22.8 (C-27 '); 22.5

(C-26 '); 21.1 (C-11 '); 20.8, 20.7, 20.6 (3 ° C-COCH3); 19.3 (C-19 '); 18.7 (C-21 '); 17.4 (C-6); 11.8 (C-18 ').

a-L-rhamnopyranoside de 17-(cholest-5-en-3p-yloxy)-3,6,9,12,15- pentaoxaheptadécyle 8

Le 2,3,4-tri-O-acétyl-a-L-rhamnopyranoside de 17-(cholest-5-èn-3p- yloxy)-3,6,9,12,15-pentaoxaheptadécyle 7 (lOOmg, 0. 12 mmole) et le méthanolate de sodium (24mg, 0,43 mmole) sont dissous dans du méthanol. Le mélange réactionnel est laissé sous agitation à température ambiante pendant 2 heures. Après l'ajout d'une solution aqueuse d'acide chlorhydrique 2N, le méthanol est évaporé sous pression réduite puis la solution est extraite au dichlorométhane puis lavée avec une solution aqueuse saturée de chlorure de sodium. La phase organique est séchée sur du sulfate de sodium anhydre puis concentrée sous vide. Le résidu obtenu est chromatographié sur colonne de gel de silice [éluant : gradient de méthanol (0-5%) dans du dichlorométhane] pour conduire au surfactant 8 sous forme de mousse blanche collante (Rdt=65%). MS (FAB + / NOBA) m / z: 945 [M + Na] +; 923 [M + H] +; 369 [M-HEG + H] +.

17- (cholest-5-en-3β-yloxy) -3,6,9,12,15-pentaoxaheptadecyl α-rhamnopyranoside 8

17- (Chlest-5-en-3p-yloxy) -3,6,9,12,15-pentaoxaheptadecyl 2,3,4-tri-O-acetyl-α-rhamnopyranoside 7 (100 mg, 0.12 mmol). ) and sodium methanolate (24 mg, 0.43 mmol) are dissolved in methanol. The reaction mixture is stirred at room temperature for 2 hours. After the addition of a 2N aqueous hydrochloric acid solution, the methanol is evaporated under reduced pressure and the solution is then extracted with dichloromethane and then washed with a saturated aqueous solution of sodium chloride. The organic phase is dried over anhydrous sodium sulphate and then concentrated in vacuo. The residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (0-5%) in dichloromethane] to give surfactant 8 in the form of a tacky white foam (yield = 65%).

Rf 0.25 (CH 2 Cl 2 / MeOH 95/5).

[UID -38 (c = 1.01, CHCl3).

1H NMR (CDCl3, 200MHz) δ (ppm): 5.33 (1H, d, J6 = S, 1Hz, H-6 '); 4.83 (1H, s, H-1); 3.95 (1H, m, H-5); (25H, m, H-CH 2 O, H-2); 3.52-3.38 (2H, m, H-3, H-4);

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d, J2l~Zp≥6,6Hz; H-21') ; 0,85 (6H, d, J26>~ZS=6,6Hz, H-26', H-27') ; 0,66 (3H, s, H- 18'). 3.29-3.12 (1H, m, H-3 '); (3H, d, J6-5 = 6.2 Hz, H-6); 0.98 (3H, s, H-19 '); 0.9 (3H,

d, J2l ~ Zp≥6.6Hz; H-21 '); 0.85 (6H, d, J26> ~ ZS = 6.6 Hz, H-26 ', H-27'); 0.66 (3H, s, H-18 ').

13C NMR (CDCl3, 50MHz)
8 (ppm): 140.9 (C-5 '); 121.6 (C-6 '); 99.9 (Cl); 79.6 (C-3 '); 73.4 (C-4); 71.7 (C-3); 70.9 (C-2); 70,8,70,6; 70,5,70,4; 70.2 (5 ° C-CH 2 O); 67.9 (C-5); 67.2 (C-CH 2 O); 66.6 (C-CH 2 O); 56.8 (C-14 '); 56.2 (C-17 '); 50.2 (C-9 '); 42.3 (C-13 '); 39.8 (C-16 '); 39.5 (C-24 '); 39 (C-4 '); 37.2 (C-1 '); 36.9 (C-10 '); 36.2 (C-22 '); 35.8 (C-20 '); 31.9 (C-7 ', C-8'); 28.3 (C-2 '); 28.2 (C-12 '); 28 (C-25 '); 24.3 (C-15 '); 23.8 (C-23 '); 22.8 (C-27 '); 22.6 (C-26 '); 21.1 (C-11 '); 19.4 (C-19 '); 18.7 (C-21 '); 17.6 (C-6); 11.9 (C-18 ').

 MS (FAB + / NOBA) m / z: 835 [M + K] +; 819 [M + Na] +; 369 [M-HEG + H] +.

B / Synthesis of Amphiphilic Glycosides 16, 17, 18 and 20 with a Lipophilic Part of Cannabinoid Type
Preparation of brominated derivatives 10, 13 and 15

To a solution of L- (+) - rhamnose 27.4 mmol) and tri (ethylene glycol) (11 ml, 82.3 mmol) in tetrahydrofuran (100 ml) is added p-toluenesulfonic acid (6.8 g, 35.7 mmol). The reaction mixture is stirred at 60 ° C. for 3 days. After adding anhydrous sodium carbonate to powder, the mixture is filtered on celite and the filtrate concentrated under reduced pressure. The crude residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (1-10%) in dichloromethane] to yield L-rhamnopyranoside of 3,6,8-trioxanonanyl 9 in the form of a colorless oil ( Yield = 68%, anomers [alpha] / ss 95/5).

Rf 0.55 (CH 2 Cl 2 / MeOH 8/2).

[a] D-38 (c = 1, CH 3 OH).

1H NMR (CD30D, 250MHz)

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8 (ppm) : 4,74 (1H, d, Ji-2=1,7Hz, H-l anomère a) ; 4,62 (1H, s, H-l anomère ss) ; 3,85-3,77 (2H, m, H-2, H-5) ; 3,71-3,58(12H, m, H-CH20) ; 3,43-3,32 (2H, m, H-3, H-4) ; 1,28 (3H, d, J6-5=6,2Hz, H-6).

Δ (ppm): 4.74 (1H, d, λ max = 1.7 Hz, H anomers a); 4.62 (1H, s, 1H anomeric ss); 3.85-3.77 (2H, m, H-2, H-5); 3.71-3.58 (12H, m, H-CH 2 O); 3.43-3.32 (2H, m, H-3, H-4); 1.28 (3H, d, J6-5 = 6.2 Hz, H-6).

 13C-NMR (CD30D, 100MHz) ((ppm): 100.8 (C-1); 72.9 (C-4); 72.7 (C-3); 71.2 (C-2); 71, 70.7, 70.4 (3 ° C-CH 2 O); 68.8 (C-5); 66.7, 6.6.2, 61.2 (3 ° C-CH 2 O); 17.1 (C-6).

MS (FAB / NOBA) m / z: 319 [M + Na] +; 297 [M + H] +; 151 [M-sugar + H] +.

8-Bromo-3,6-dioxaoctanyl L-rhamnopyranoside
To a solution of compound 9 (2.4 g, 7.7 mmol) and tetrabromomethane (5.1 g, 15.3 mmol) in anhydrous tetrahydrofuran (100 ml) is added triphenylphosphine (4 g, 15.3 mmol). . The reaction mixture is stirred at room temperature for 14 hours. After filtration, the solution is concentrated under vacuum and the crude residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (1-5%) in dichloromethane]. The 8-bromo-3,6-dioxaoctanyl Lrhamnopyranoside is obtained in the form of a colorless oil (yield = 55%, [alpha] / ss anomers: 90/10).

RMN tH (CDCI3, 250MHz) # (ppm) : 4,83 (1H, s, H-1 anomère a) ; 4,55 (1H, s, H-1 anomère p) ; 4,13-3,99 (2H, m, H-2, H-5) ; 3,87-3,68(12H, m, H-CH20) ; 3,43-3,32 (4H, m, H-OCH2CH2Br, H-3, H-4) ; (3H, d, J6-5=6,lHz, H-6 anomère a) ; 1,28

(3H, d, J6~5=6,2Hz, H-6 anomère P). Rf 0.42 (CH 2 Cl 2 / MeOH 9/1). [a] D -42 (c = 1, CHCl3).

1H NMR (CDCl3, 250MHz) # (ppm): 4.83 (1H, s, H-1 anomer a); 4.55 (1H, s, H-1 anomer p); 4.13-3.99 (2H, m, H-2, H-5); 3.87-3.68 (12H, m, H-CH 2 O); 3.43-3.32 (4H, m, H-OCH2CH2Br, H-3, H-4); (3H, d, J6-5 = 6, 1Hz, H-6 anomer a); 1.28

(3H, d, J6 ~ 5 = 6.2 Hz, H-6 P-anomer).

OCH2CH2Br) ; 30,8 (C-OCH2ÇH2-Br) ; 18 (C-6). 13C NMR (CDCl3,100MHz) # (ppm): 100.4 (Cl); 73.1 (C-4); 72 (C-3); 71.6 (C-CH 2 O); 71.2 (C-2); 70.9, 70.6, 70.1 (3 ° C-CH 2 O); 68.6 (C-5); 66.9 (C-CH 2 O); 61.2 (C-

OCH2CH2Br); 30.8 (C-OCH2CH2-Br); 18 (C-6).

MS (FAB + / NOBA) m / z: 743 [2M 81 Br + Na] +; 739 [2M9Br + Na] +; 383

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[M8IBr+Nat; 381 [M9Br+Na]+; 361 [M8IBr+Ht; 359 [M9Br+H]+.

[M8IBr + Nat; 381 [M9Br + Na] +; 361 [M8IBr + Ht; 359 [M9Br + H] +.

3,6,8-trioxanonanyl L-fucopyranoside 11 To a solution of L- (+) - fucose (1.8 g, 11 mmol) and tri (ethylene glycol) (4.5 ml, 32.9 mmol) in tetrahydrofuran (40 ml) is added p-toluenesulfonic acid (3.6 g, 21.9 mmol). The reaction mixture is stirred at 55 ° C. for 1 day. After adding anhydrous sodium carbonate to powder, the mixture is filtered on celite and the filtrate concentrated under reduced pressure. The crude residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (1-5%) in dichloromethane] to give L-fucopyranoside of 3,6,8-trioxanonanyl 11 in the form of a colorless oil ( Yield = 68%, anomers [alpha] / ss 36/64).

Rf 0.35 (CH 2 Cl 2 / MeOH 9/1).

[?] -23.5 (c = 1, CHCl3).

anomère a : ô (ppm) : 4,83 (1H, d, JI-2=4,6Hz, H-l) ; 4,6 (1H, m, H-CH20H) ; 4-3,5 (16H, m, H-2, H-3, H-4, H-5, H-CH20) ; 1,25 (3H, d, J6-5=6,4Hz, H-6).

anomère [i : 5 fppm) : 4,6 (1H, m, H-CH20H) ; 4,2 (1H, d, Ji.2=7,4Hz, H-l) ; 4-3,5 (16H, m, H-2, H-3, H-4, H-5, H-CH20) ; 1,3 (3H, d, J6-s=6,6Hz, H-6).

RMN 13C (CDCI3,100MHz) anomère a : # (ppm) : 101 (C-l) ; 74,5 (C-4) ; 72,4 (C- CH20) ; 71 (C-3, C-2) ; 70-69,6(3*C-CH20) ; 67,5 (C-CH2CH20H) ; 67 (C-5) ; 61 (C-CH20H) ; 19 (C-6). anomère p : 5 (ppm) : 103 (C-l) ; 73,6 (C-4) ; 72,5 (C-CH20) ; 71,4 (C-3) ; 70,5 (C-2) ; 70-69,6 (3*C-CH20) ; 68 (C-CH2CH20H) ; 66,9 (C-5) ; 61,7 (C-CH20H) ; 19,3 (C-6).

1H NMR (CDCl3, 400MHz)

anomer a: δ (ppm): 4.83 (1H, d, JI-2 = 4.6 Hz, H1); 4.6 (1H, m, H-CH 2 OH); 4-3.5 (16H, m, H-2, H-3, H-4, H-5, H-CH 2 O); 1.25 (3H, d, J6-5 = 6.4Hz, H-6).

anomer [i: 5 ppm]: 4.6 (1H, m, H-CH 2 OH); 4.2 (1H, d, Ji.2 = 7.4Hz, H1); 4-3.5 (16H, m, H-2, H-3, H-4, H-5, H-CH 2 O); 1.3 (3H, d, J6-s = 6.6Hz, H-6).

13C NMR (CDCl3,100MHz) anomer a: # (ppm): 101 (Cl); 74.5 (C-4); 72.4 (C-CH 2 O); 71 (C-3, C-2); 70-69.6 (3 * C-CH 2 O); 67.5 (C-CH 2 CH 2 OH); 67 (C-5); 61 (C-CH 2 OH); 19 (C-6). anomer p: (ppm): 103 (Cl); 73.6 (C-4); 72.5 (C-CH 2 O); 71.4 (C-3); 70.5 (C-2); 70-69.6 (3 * C-CH 2 O); 68 (C-CH 2 CH 2 OH); 66.9 (C-5); 61.7 (C-CH 2 OH); 19.3 (C-6).

MS (ESI + / ESI730eV) m / z: 318 [M + Na] +. m / z: 295 [M-H] -.

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L-fucopyranoside 8-bromo-3,6-dioxanoctanyl 12
To a solution of 3,6,8-trioxanonanyl L-fucopyranoside 11 (0.5 g, 1.7 mmol), N-bromosuccinimide (0.9 g, 5.1 mmol) and triphenylphosphine (1.3 g, m.p. 1 mmol) in dimethylformamide (13 ml) is stirred at 55 ° C. for 3 hours. After adding methanol, the solvents are evaporated off under reduced pressure and the residue obtained is taken up in dichloromethane and washed with water. The organic phase is dried over anhydrous sodium sulphate and then concentrated in vacuo. The residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (0-4%) in dichloromethane] to yield L-fucopyranoside of 8-bromo-3,6-dioxanoctanyl 12 in the form of an oil yellow (Yield = 65%, anomers a / (3 70/30).

Rf 0.5 (CH 2 Cl 2 / MeOH 95/5).

[?] D -27.6 (c = 1.05, CHCl3).

1H NMR (CDCl3, 200MHz) δ (ppm): 4.81 (1H, s, H-1 anomer a); 4.19 (1H, d, JI-2 = 7Hz, H-1 anomer / 3); 3.75 (2H, t, JOCH2-CH2Br = 6.2Hz, H-OCfuCH2Br); 3.65-3.53 (12H, m, H-CH 2 O, H-2, H-3, H-4, H-5); 3.42 (2H, t, JOCH2-CH2Br = 6.2Hz, H-OCH2CH2Br); 2.23 (2H, m, OH); (3H, d, J6-5 = 7.2 Hz, H-6).

13C NMR (CDCl3,100MHz)
Δ (ppm): 100.8 (C-1); 72.9 (C-4); 72.7 (C-3); 71.2 (C-2); 71.70.7, 70.4 (3 ° C-CH 2 O); 68.8 (C-5); 66.7, 66.2, 61.2 (3 ° C-CH 2 O); 17.1 (C-6).

m/z : 373 [M8IBr+Nat ; 371 [M79Br+Na]+ ; 279 [M-Br]+ ; 147 [M-TEGBr]+.

2,3,4-tri-O-acétyl-a-L-rhamnopyranoside de 3,6,9,12,15,18-hexaoxaoctadécyle 13 MS (FAB + / NOBA)

m / z: 373 [M8IBr + Nat; 371 [M79Br + Na] +; 279 [M-Br] +; 147 [M-TEGBr] +.

2,3,4,12,15,18-hexaoxaoctadecyl 2,3,4-tri-O-acetyl-α-rhamnopyranoside 13

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To a solution of compound 6 (4.5 g, 13.6 mmol) and hexa (ethylene glycol) (5 g, 17.6 mmol) dissolved in anhydrous dichloromethane (90 ml) is added dropwise the trifluoride etherate. boron (11.5 ml, 90.8 mmol). The reaction mixture is stirred at room temperature for 7 hours. It is then washed with a saturated aqueous solution of sodium hydrogencarbonate and then with water. The organic phase is dried over anhydrous sodium sulphate and then concentrated in vacuo. The residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (0-3%) in dichloromethane] to yield compound 13 in the form of a colorless oil (yield = 55%).

Rf 0.55 (CH 2 Cl 2 / MeOH 95/5).

 [?] D -36.2 (c = 1.01, CHCl3).

4,77 (1H, d, JI-2=1,3Hz, H-1) ; 3,93 (1H, dd, J5=9,8Hz, JS~6=6,3Hz, H-5) ; 3,68-3,51 (24H, m, H-CH20) ; 2,6 (1H, m, OH) ; (9H, s, H-COCH3) ; (3H, d, J6-5=6,2Hz, H-6). 1H NMR (CDCl3, 250MHz) δ (ppm): 5.29 (1H, dd, J3-4 = 9.8Hz, J3-2 = 3.5Hz, H-3); 5.24 (1H, dd, J2-3 = 3.5Hz, J2-1 = 1.7Hz, H-2); 5.06 (1H, dd, J4-5 = 9.9Hz, J4-3 = 9.7Hz, H-4);

4.77 (1H, d, JI-2 = 1.3 Hz, H-1); 3.93 (1H, dd, J5 = 9.8Hz, JS-6 = 6.3Hz, H-5); 3.68-3.51 (24H, m, H-CH 2 O); 2.6 (1H, m, OH); (9H, s, H-COCH3); (3H, d, J6-5 = 6.2 Hz, H-6).

13 C NMR (CDCl3, 50MHz) δ (ppm): 170.1, 170, 169.9 (3 ° C-COCH3); 97.6 (Cl); 72.8 (C-4) 71.2 (C-3); 70.7 (C-2); 70.5, 70.4, 70.2, 70, 69.9 (6 ° C-CH 2 O); 69.2 (C-5); 67.1 (C-CH 2 O); 66.3 (C-CH 2 O); 61.6 (C-OCH 2 CH 2 OH); 20.9.20.8, 20.7 (3 ° C-COCH3); 17.4 (C-6).

MS (ESI + / ESI730eV) m / z: 577 [M + Na] +. m / z: 553 [MH] -.

17-Bromo-3,6,9,12,15-pentaoxaheptadecyl 2,3,4-tri-O-acetyl-α-Lhamnopyranoside 14
A solution of 3,6,9,12,15,18-hexaoxaoctadecyl 2,3,4-tri-O-acetyl-α-Lhamnopyranoside 13 (1 g, 1.8 mmol), N-bromosuccinimide

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(642 mg, 3.6 mmol) and triphenylphosphine (946 mg, 3.6 mmol) in dimethylformamide is stirred at 65 ° C for 3 hours. After adding methanol, the solvents are evaporated off under reduced pressure and the residue obtained is taken up in dichloromethane and washed with water. The organic phase is dried over anhydrous sodium sulphate and then concentrated in vacuo. The residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (0-2%) in dichloromethane] to give compound 14 in the form of a yellow oil (yield = 90%).

Rf 0.75 (CH 2 Cl 2 / MeOH 95/5). [[alpha]] D -32.5 (c = 1, CHCl3).

RMN 13C (CDC13, SOMHz) # (ppm) : 170,169,9, 169,8 (3*C-COCH3) ; 97,5 (C-l) ; 71,1 (C-4) ; 71 (C-3) ; 70,6 (C-CH20) ; 70,5 (C-2) ; 70,5,70,4, 70,69,9 (4*C-CH20) ; 69,1 (C-5) ; 67 (C-CH20) ; 66,2 (C-CH20) ; 29,6 (C-OCH2ÇH2Br) ; 20,8, 20,7, 20,6 (3*C-

COÇH3) ; 17,4 (C-6). 1H NMR (CD Ch, 200MHz) δ (pum): 5.27 (1H, dd, J3-4 = 9.8Hz, J3-2 = 3.5Hz, H-3); 5.23 (1H, dd, J2-3 = 3.5Hz, h = 1.7Hz, H-2); 5.04 (1H, dd, J4-5 = 9, gHz, J4-3 = 9.8 Hz, H-4); 4.76 (1H, d, JI-2 = 1.3 Hz, H1); 3.91 (1H, dd, J5-4 = 9.7 Hz, J5.6 = 6.4 Hz, H-5); 3.71-3.6 (22H, m, H-CH 2 O); 3.45 (2H, m, H-OCH2CH2Br); 2.12-1.96 (9H, s, H-COCH3); 1.2 (3H, d, J6-5 = 6.4Hz, H-6).

13 C NMR (CDCl 3, SOMHz) δ (ppm): 170.169.9, 169.8 (3 ° C-COCH 3); 97.5 (Cl); 71.1 (C-4); 71 (C-3); 70.6 (C-CH 2 O); 70.5 (C-2); 70.5, 70.4, 70.69 (4 * C-CH 2 O); 69.1 (C-5); 67 (C-CH 2 O); 66.2 (C-CH 2 O); 29.6 (C-OCH2H2Br); 20.8, 20.7, 20.6 (3 * C)

COHH3); 17.4 (C-6).

a-L-rhamnopyranoside de 17-bromo-3,6,9,12,15-pentaoxaheptadécyle 15
Le 2,3,4-tri-O-acétyl-a-L-rhamnopyranoside de 17-bromo- 3,6,9,12,15-pentaoxaheptadécyle 14 (1,37g, 2,19 mmoles) et le méthanolate de sodium (236mg, 4,37 mmoles) sont dissous dans du méthanol. Le mélange réactionnel est laissé sous agitation à température ambiante pendant 2 heures. Après addition d'acide citrique en poudre jusqu'à neutralité, de la silice est ajoutée au milieu réactionnel qui est ensuite concentré sous pression réduite. Le résidu obtenu est MS (FAB + / NOBA) m / z: 640 [M + Na] +; 618 [M + H] +.

17-Bromo-3,6,9,12,15-pentaoxaheptadecyl α-Lhamnopyranoside 15
17-Bromo-3,6,9,12,15-pentaoxaheptadecyl 2,3,4-tri-O-acetyl-α-Lhamnopyranoside (1.37 g, 2.19 mmol) and sodium methanolate (236 mg 4.37 mmol) are dissolved in methanol. The reaction mixture is stirred at room temperature for 2 hours. After adding citric acid powder to neutrality, silica is added to the reaction medium which is then concentrated under reduced pressure. The residue obtained is

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chromatographed on silica gel column [eluent: gradient of methanol (0-5%) in dichloromethane] to yield 17-bromo- 3,6,9,12,15-pentaoxaheptadecyl α-L-rhamnopyranoside 15 in the form of a colorless oil (Yield = 65%).

Rf 0.15 (CH 2 CH / MeOH 95/5).

[?] D -29 (c = 1.03, CHCl3).

J2-3=3,5Hz, J2.,=l,8Hz, H-2) ; 3,87-3,6 (25H, m, H-3, H-4, H-5, H-CH20) ; 3,45 (2H, m, H-OCH2CH2Br) ; 2,83-1,85 (3H, m, OH) ; 1,31 (3H, d, J6-5=6,2Hz, H-6).

RMN 13C (CDCl3, 50MHz) # (ppm) : 100 (C-l) ; 72,5 (C-4) ; 71,3 (C-3) ; 71,1 (C-CH20) ; 70,6 (C-2) ; 70,6,70,4, 70 (3*C-CH20) ; 68,2 (C-5) ; 67 (C-CH20) ; 66,2 (C-CH20) ; 30,4 (C-OCH2CH2Br) ; 17,5 (C-6). 1H NMR (CDCl3, 200MHz) # (ppm): 4.85 (1H, d, JI-2 = 1.5Hz, H1); 3.97 (1H, dd,

J2-3 = 3.5 Hz, J2, = 1.8 Hz, H-2); 3.87-3.6 (25H, m, H-3, H-4, H-5, H-CH 2 O); 3.45 (2H, m, H-OCH2CH2Br); 2.83-1.85 (3H, m, OH); 1.31 (3H, d, J6-5 = 6.2 Hz, H-6).

13 C NMR (CDCl 3, 50MHz) ((ppm): 100 (Cl); 72.5 (C-4); 71.3 (C-3); 71.1 (C-CH 2 O); 70.6 (C-2); 70.6, 70.4, 70 (3 ° C-CH 2 O); 68.2 (C-5); 67 (C-CH 2 O); 66.2 (C-CH 2 O); 30.4 (C-OCH2CH2Br); 17.5 (C-6).

m/z : 515 [M8IBr+Nat ; 513 [M79 Br+Na]+ ; 493 [M8lBr]+ ; 491 [M9Br]+; 347 [M8IBr-sucre+Ht; 345 [M79Br-sucre+H]+. C/ Préparation des dérivés de type cannabinoïde 16 et 17

MS (FAB + / NOBA)

m / z: 515 [M8IBr + Nat; 513 [M79 Br + Na] +; 493 [M8IBr] +; 491 [M9Br] +; 347 [M8IBr-sugar + Ht; 345 [M79Br-sugar + H] +. C / Preparation of Cannabinoid Derivatives 16 and 17

A solution of phloroglucinol (6 g, 37 mmol) and freshly distilled citral (7 mL, 40.7 mmol) in anhydrous pyridine (3.6 mL, 44.4 mmol) is refluxed for 6 hours. After cooling, the medium is diluted with chloroform and the solution is washed with a 10% aqueous solution of hydrochloric acid and with water. The organic phases are dried over anhydrous sodium sulphate and then concentrated under reduced pressure. The crude residue obtained is chromatographed on a column of silica gel [eluent: petroleum ether / ethyl ether 9/1]. Citrylidene phloroglucinol 16 is thus obtained in the form of a powder

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 white which is recrystallized from a mixture of petroleum ether / dichloromethane (yield = 40%).

 Rf 0.51 (EP 5 / Et 5/5).

 Mp 151-152 C.

ddd, J9-8a=3,2Hz, J9-12=2,7Hz. J9-sp=l,7Hz, H-9) ; 2,23 (1H, ddd, J8 ~8p=13,3Hz, J8a.9=3,2Hz, J8 ~o=l,6Hz, H-8a) ; 2,03 (1H, ddd, J12-llp=11,4Hz, 32~1 S,IHz, J12-9=2,7Hz, H-12) ; 1,83 (1H, dd, J8a-8p=13,2Hz, J8p~9=l,7Hz, H-8p) ; 1,74 (1H, ddd, Jiop-ioa=13,5Hz, JJOI3-1113=5,7Hz, Jlpp~8 3,lHz, H-10(3} ; 1,54 (3H, s, H-14) ; 1,45 (1H, dt, JJOa-I0I3=13,5Hz, Jo ~,IR=13,3Hz, Joa~ll 5,3Hz, H-10a) ; 1,39 (3H, s, H-16) ; 1,24 (1H, dt, J11 ~y=13,3Hz, Jl,a~lo 5,3Hz, JI .i2=5,lHz, H-lla) ; 1,05 (3H, s, H-15) ; 0,69 (1H, dddd, Jnp-loa=13,5Hz, Jlp~,1 13,3Hz, Jnp.i2=ll,4Hz, Jnp.10p=5,7Hz, H- 11ss).

RMN 13C (CDCI3,100MHz) 8(ppm) : 157,8 (C-1) ; 157,5 (C-5) ; 156 (C-3) ; 109,8 (C-6) ; 98,9 (C-4) ; 97,3 (C-2) ; 85(C-7) ; 75,5 (C-13) ; 47,1 (C-12) ; 37,7 (C-10) ; 35,7 (C-8) ; 30 (C-14) ; 29,4 (C-16) ; 28,1 (C-9) ; 24,2 (C-15) ; 22,4 (C-l 1). 1H NMR (CDCl3, 250MHz) δ (ppm): 6.04 (2H, s, H-2, H-4); 4.77 (1H, s, OH); 2.84 (1H,

ddd, J9-8a = 3.2Hz, J9-12 = 2.7Hz. J9-sp = 1.7 Hz, H-9); 2.23 (1H, ddd, J8 ~ 8p = 13.3Hz, J8a.9 = 3.2Hz, J8 ~ 0 = 1.6Hz, H-8a); 2.03 (1H, ddd, J12-11p = 11.4Hz, 32-1S, IHz, J12-9 = 2.7Hz, H-12); 1.83 (1H, dd, J8a-8p = 13.2Hz, J8p-9 = 1.7Hz, H-8p); 1.74 (1H, ddd, Jiop-ioa = 13.5Hz, JJOI3-1113 = 5.7Hz, Jlpp ~ 8.3, 1Hz, H-10 (3), 1.54 (3H, s, H-14) 1.45 (1H, dt, JJOa-IOI3 = 13.5Hz, Jo ~, IR = 13.3Hz, Joa ~ 11 5.3Hz, H-10a); 1.39 (3H, s, H-16); 1.24 (1H, dt, J11-y = 13.3Hz, J1, at ~ 5.3Hz, J1 · 12 = 5.1Hz, H-11a); 1.05 (3H, s, H-15); 0.69 (1H, dddd, Jnp-loa = 13.5Hz, Jlp ~, 13.3Hz, Jnp.i2 = 11.4Hz, Jnp.10p = 5.7Hz, H-11ss).

13 C NMR (CDCl3,100MHz) δ (ppm): 157.8 (C-1); 157.5 (C-5); 156 (C-3); 109.8 (C-6); 98.9 (C-4); 97.3 (C-2); 85 (C-7); 75.5 (C-13); 47.1 (C-12); 37.7 (C-10); 35.7 (C-8); (C-14); 29.4 (C-16); 28.1 (C-9); 24.2 (C-15); 22.4 (Cl 1).

MS (FAB + / NOBA) m / z: 261 [M + H] +; 177 [M-C6H11] +.

 To a cooled solution at 0 ° C. of olivetol (1 g, 5.6 mmol), p-mentha-2,8-dien-1-ol (850 mg, 5.6 mmol) and anhydrous magnesium sulfate (695 mg, 5.8 mmol) in anhydrous dichloromethane (35 ml) is added dropwise boron trifluoride etherate (0.35 ml, 2.8 mmol). After stirring at 0 ° C. for 1 h 30 min, anhydrous sodium hydrogencarbonate (1.7 g, 5.6 mmol) is then added and the brown solution is stirred until an orange color is obtained. After filtration, the filtrate is concentrated under vacuum and the residue is

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 chromatographed on a column of fluorisil gel [eluent: gradient of ethyl ether (0-2%) in petroleum ether] to give compound 17 in the form of orange gum (yield = 18%).

 Rf 0.3 (EP / Et2O 95/5).

 [?] D-159 (c = 1, CHCl 3).

S (ppm) : 6,32 ( 1 H, s, H-4) ; 6,27 ( 1 H, s, H-2) ; 6,14 ( 1 H, d, Jio-lo,.=I,SHz, H-10) ; 4,96 (1H, s, OH) ; 3,21 (1H, dd, Jioa-6a=l llHz, Jlocc-lo=l,8Hz, H- 10a) ; 2,44 (2H, t, JI'-2,=7,6Hz, H-l') ; 2,15 (2H, m, H-8) ; 1,92 (1H, m, H-6a) ; 1,68

(3H, s, H-ll) ; 1,56 (2H, q, J2~l=7,4Hz, H-2') ; 1,42 (3H, s, H-6a) ; 1,33-1,23 (6H, m, H-7, H-3', H-4') ; 1,10 (3H, s, H-6p) ; 0,88 (3H, t, JS=6,4Hz, H-5'). 1H NMR (CDCl3, 200MHz)

S (ppm): 6.32 (1H, s, H-4); 6.27 (1H, s, H-2); 6.14 (1H, d, JI-10, I = SHz, H-10); 4.96 (1H, s, OH); 3.21 (1H, dd, Jiaa-6a = 11Hz, Jlocc-lo = 1.8Hz, H-10a); 2.44 (2H, t, JI-2, = 7.6 Hz, H-1 '); 2.15 (2H, m, H-8); 1.92 (1H, m, H-6a); 1.68

(3H, s, H-11); 1.56 (2H, q, J2 ~ 1 = 7.4 Hz, H-2 '); 1.42 (3H, s, H-6a); 1.33-1.23 (6H, m, H-7, H-3 ', H-4'); 1.10 (3H, s, H-6p); 0.88 (3H, t, JS = 6.4Hz, H-5 ').

13 C NMR (CDCl 3,100MHz) δ (ppm): 155.1 (C-1); 154.7 (C-4a); 143.2 (C-3); 134.8 (C-9); 124.2 (C-10); 110.4 (C-4); 109.5 (C-10p); 108 (C-2); 77.8 (C-6); 46.2 (C-6a); 35.9 (C-1 '); 34 (C-10a); 32 (C-7); 31.6 (C-2 '); 31.1 (C-3 '); 28 (C-6 (3); 25.5 (C-8); 23.8 (Cl 1); 23 (C-4 '); 19.7 (C-6a); 14.5 (C-5); ').

 MS (FAB + / NOBA) m / z: 315 [M + H] +; 314 [M] +; 299 [M-CH3] +; 231 [MC6H11] +.

D / Synthesis of amphiphilic glycosides 18, 19, 20, 21 and 23
1- General Procedure for the Synthesis of Amphiphilic Glycosides 18, 19, 20 and 21 According to a Williamson-type Reaction
A solution of phenol derivative (1 mmol) and anhydrous cesium carbonate (3 mmol) in anhydrous dimethylformamide (5 ml) is stirred at 70 ° C. for 1 hour. Then the brominated derivative (2 mmol) dissolved in anhydrous dimethylformamide (5 ml) is added at 50 ° C. and the reaction mixture is left at this temperature for 3 hours. Then a saturated solution of sodium chloride is added and the aqueous phase is extracted 3 times with dichloromethane. The organic phases are dried over anhydrous sodium sulphate and then concentrated under reduced pressure. The residue obtained is each time purified by column chromatography on silica gel. The elution conditions and the yield of each compound are given below.

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L-rhamnopyranoside of 8-citrylidene phloroglucinyl-3,6-dioxaoctanyl 18
Elution with a gradient of methanol (0-5%) in dichloromethane gives L-rhamnopyranoside of 8-citrylidene phloroglucinyl-3,6dioaxaoctanyl 18 as a sticky white foam (Yield = 65%, anomers [alpha] / ss 90/10).

Rf 0.37 (CH 2 Cl 2 / MeOH 95/5).

[a] D -31 (c = 1, CHCl3).

J9-i2=2,7Hz, J9-sp=l,7Hz, H-9) ; 2,23 (1H, ddd, Jga~8p=13,3Hz, J8,-9=3,2Hz, J8a-iop=l,6Hz, H-8a) ; 2,03 (1H, ddd, J12-11=11,4Hz, J12-11,=5,lHz, J2~9=2,7Hz, H- 12) ; 1,83 (1H, dd, J8a.8p=13,2Hz, J8p.9=l,7Hz, H-8p) ; 1,74 (1H, ddd, Jlop~o 13,SHz, JIOI3-1113=5,7Hz, Jiop-8a=3,lHz, H-10(3) ; 1,54 (3H, s, H-14) ; 1,45 (1H, dt, JJOaiop=13,5Hz, Jloa-n=13,3Hz, J1Oa-Ha=5,3Hz, H-lOa) ; 1,39 (3H, s, H-16) ; 1,28 (3H, d, J6-5=6,2Hz, H-6) ; 1,24 (1H, dt, Jlla-lp=13,3Hz, JIa~to 5,3Hz, Jna.,2=5,lHz, H-l la) ; 1,05 (3H, s, H-15) , 0,69 (1H, dddd, Jlip.,oa=13,5Hz, Jil-y13,3Hz, Jllp-12=11,4Hz, Jlll3-1013=5,7Hz, H-11). 1 H NMR (CDCl3, 250MI-1Hz) (ppm): 6.04 (2H, s, H-2, H-4); 4.74 (1H, d, J1-2 = 1.7Hz, H-1 anomer a); 4.62 (1H, s, H-1 anomer (3); 3.85-3.77 (2H, m, H-2, H-5); 3.71-3.58 (12H, m, H -CH 2 O); 3.43-3.32 (2H, m, H-3, H-4); 2.84 (1H, ddd, J9-sa = 3.2 Hz,

J9 -12 = 2.7Hz, J9-sp = 1.7Hz, H-9); 2.23 (1H, ddd, Jga ~ 8p = 13.3Hz, J8, -9 = 3.2Hz, J8a-iop = 1.6Hz, H-8a); 2.03 (1H, ddd, J12-11 = 11.4Hz, J12-11, = 5.1 Hz, J2 ~ 9 = 2.7Hz, H-12); 1.83 (1H, dd, J8a.8p = 13.2Hz, J8p.9 = 1.7Hz, H-8p); 1.74 (1H, ddd, Jlop-o 13, SHz, JIOI3-1113 = 5.7Hz, Jiop-8a = 3.1Hz, H-10 (3), 1.54 (3H, s, H-14) 1.45 (1H, dt, JJOaiop = 13.5Hz, Jloa-n = 13.3Hz, J10a-Ha = 5.3Hz, H-10a), 1.39 (3H, s, H-16); , 28 (3H, d, J6-5 = 6.2 Hz, H-6), 1.24 (1H, dt, Jlla-1p = 13.3Hz, JIa ~ to 5.3Hz, Jna., 2 = 5, 1Hz, H1a) 1.05 (3H, s, H-15), 0.69 (1H, dddd, Jlip., oa = 13.5Hz, Jil-y13.3Hz, J11p-12 = 11.4Hz, J1113-1013 = 5.7 Hz, H-11).

CH20) ; 66,9 (C-CH2O) ; 47,1 (C-12') ; 37,7 (C-10') ; 35,7 (C-8') ; 30,1 (C-14') ; 29,4 (C-16') ; 28,2 (C-9') ; 24,2 (C-15') ; 22,4 (C-11') ; 18 (C-6). 13 C NMR (CDCl 3 · 100MHz) δ (ppm): 159.2 (C-3 '); 157.9 (C-5 '); 157.5 (C-1 '); 110.1 (C-6 '); 100.3 (Cl); 98.3 C-4 '); 98.2 (C-2 '); 84.6 (C-7 '); 75.3 (C-13 '); 73.4 (C-4); 72.1 (C-3); 71.3 (C-2); 71.2, 70.9, 70.6, 70.1 (4 * C-CH 2 O); 68.5 (C-5); 68 (C-

CH20); 66.9 (C-CH2O); 47.1 (C-12 '); 37.7 (C-10 '); 35.7 (C-8 '); 30.1 (C-14 '); 29.4 (C-16 '); 28.2 (C-9 '); 24.2 (C-15 '); 22.4 (C-11 '); 18 (C-6).

 MS (FAB + / NOBA) m / z: 561 [M + Na] +; 539 [M + H] +.

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L-fucopyranoside 8-citrylidene phloroglucinyl-3,6-dioxaoctanyl 19
Elution with a gradient of methanol (0-6%) in dichloromethane leads to L-fucopyranoside of 8-citrylidene phloroglucinyl-3,6dioaxaoctanyl 19 as a sticky white foam (Yield = 68%, anomers [alpha] / ss 75/25).

 Rf 0.55 (CH2Cl2 / MeOH 92/8).

RMN 'H (CDC13, 250MHz) # (ppm) : 6,05 (2H, s, H-2, H-4) ; 4,86(1H, s, H-l anomère a) ; 4,23 (1H, d, JI-2=7Hz, H-l anomère P) ; 4,05-3,98 (3H, m, H-OCH2CH2OAr, H- 5) ; 3,83-3,66 (13H, m, H-CH20, H-2, H-3, H-4) ; 3,3(1H, s, OH) ; 2,98(1H, s, OH) ;

2,79 (1H, ddd, J9-8,=3,2Hz, J9-12=2,7Hz, Jg-8=1,7Hz, H-9) ; 2,17 (1H, ddd, J8a~8a=13,2Hz, J8a~9=3,SHz, Jsct-lop=1,6Hz, H-8a) ; 1,97 (1H, ddd, Ji2.np=ll,6Hz, J12na=5,lHz, J12-9=2,6Hz, H-12) ; 1,83 (1H, dd, J8,-85=13,2HZ, J8-9=1,7Hz, H-8p) ; 1,74 (1H, ddd, Jio-lo,=13,5Hz, Jop~np=5,7Hz, J,op-ga=3,lHz, H-10P) ; 1,48 (3H, s, H-14) ; 1,45 (1H, dt, Jioa-rop=13,SHz, Jloa~np=13,3Hz, Jio.-,,,,.=5,3Hz, H-10a) ; 1,34 (3H, s, H- 16) ; 1,24 (1H, dt, Jlla.np=13,3Hz, Jlla-IOa=5,3Hz, J,la.12=5,lHz, H-l la) ; 1,24 (3H, d, J6-5=6,6Hz, H-6) ; 0,99 (3H, s, H-15); 0,58 (1H, dddd, Jy~o=13,SHz, JllplIa=13,3Hz, Jnp.,2=ll,4Hz, J lIP-IOp=5,7Hz, H-11(3). [a] D -29.5 (c = 1.1 CHCl3)

1 H NMR (CDCl 3, 250MHz) δ (ppm): 6.05 (2H, s, H-2, H-4); 4.86 (1H, s, 1H anomeric a); 4.23 (1H, d, JI-2 = 7Hz, H1 P-anomer); 4.05-3.98 (3H, m, H-OCH2CH2OAr, H-5); 3.83-3.66 (13H, m, H-CH 2 O, H-2, H-3, H-4); 3.3 (1H, s, OH); 2.98 (1H, s, OH);

2.79 (1H, ddd, J9-8, = 3.2Hz, J9-12 = 2.7Hz, Jg-8 = 1.7Hz, H-9); 2.17 (1H, ddd, J8a ~ 8a = 13.2Hz, J8a ~ 9 = 3, SHz, Jsct-lop = 1.6Hz, H-8a); 1.97 (1H, ddd, Ji2.np = 11.6Hz, J12na = 5.1Hz, J12-9 = 2.6Hz, H-12); 1.83 (1H, dd, J8, -85 = 13.2HZ, J8-9 = 1.7Hz, H-8p); 1.74 (1H, ddd, Jio-lo, = 13.5Hz, Jop-np = 5.7Hz, J, op-ga = 3.1Hz, H-10P); 1.48 (3H, s, H-14); 1.45 (1H, dt, Jioa-rop = 13, SHz, Jloa ~ np = 13.3Hz, JI0.5.1, 5.3Hz, H-10a); 1.34 (3H, s, H-16); 1.24 (1H, dt, J11a.np = 13.3Hz, Jlla-10a = 5.3 Hz, J, la.12 = 5.1 Hz, Hl la); 1.24 (3H, d, J6-5 = 6.6 Hz, H-6); 0.99 (3H, s, H-15); 0.58 (1H, dddd, Jy-o = 13, SHz, JllplIa = 13.3Hz, Jnp., 2 = 11.4Hz, JIP-IOp = 5.7Hz, H-11 (3).

 13C NMR (CDCl3,100MHz) # (ppm): 159.2 (C-3 '); 158 (C-5 '); 157.5 (C-1 '); 110.1 (C-6 '); 102.5 (C-1 anomer P); 99.5 (C-1 anomer a); 98.1 (C-4 '); 96 (C-2 '); 84.6 (C, 7 '); 75.3 (C-13 '); 72.3 (C-4); 71.5 (C-3); 71.1, 70.8, 70.6, 70 (4 * C-CH 2 O); 69.6 (C-2); 67.9 (C-CH 2 O); 67.8 (C-CH 2 O); 66.5 (C-5); 47 (C-12 '); 37.7 (C-10 '); 35.6 (C-8 '); (C-14 '); 29.4 (C-16 '); 28.1 (C-9 '); 24.1 (C-15 '); 22.4 (C-11 '); 16.8 (C-6 anomer p), 16.6 (C-6 anomer a).

m/z : 561 [M+Na]+ ; 539 [M+H]+; 455 [M-C6H,,]+; 260 [M-sucre- TEG]+. MS (FAB + / NOBA)

m / z: 561 [M + Na] +; 539 [M + H] +; 455 [M-C6H ,,] +; 260 [M-sugar-TEG] +.

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a-L-rhamnopyranoside de 8-(d9)-tétrahydrocannabinoyl-3,6-dioxaoctanyle 20 L'élution par un gradient de méthanol (0-3%) dans du dichlorométhane conduit à l'a-L-rhamnopyranoside de 8-(d9)-tétrahydrocannabinoyl- 3,6-dioaxaoctanyle 20 sous forme de mousse blanche collante (Rdt=65%).
Rf 0,25 (CH2C12/MeOH 97/3).

8- (d9) -tetrahydrocannabinoyl-3,6-dioxaoctanyl aL-rhamnopyranoside Elution with a gradient of methanol (0-3%) in dichloromethane leads to α-L-rhamnopyranoside of 8- (d9) tetrahydrocannabinoyl-3,6-dioaxaoctanyl in the form of a tacky white foam (yield = 65%).
Rf 0.25 (CH 2 Cl 2 / MeOH 97/3).

[a] D -120 (c = 1, CHCl 3).

(6H, m, H-7', H-3", H-4") ; 1,3 (3H, d, J6-5=4,4Hz, H-6) ; 1,10 (3H, s, H-6'p) ; 0,88 (3H, t, J5"-4"=6,6Hz, H-5"). 1 H NMR (CDCl 3, 200MHz) δ (ppm): 6.31 (1H, s, H-4 '); 6.23 (bs, s, H-2 '); 6.14 (1H, d, JI0-JOa = 1, 8Hz, H-10 '); 4.78 (1H, d, JI-2 = 5.1Hz, H1); 4.14-3.41 (16H, m, H-CH 2 O, H-2, H-3, H-4, H-5); 3.17 (1H, dd, Jloa-6a = 9.9Hz, J10a-10 = I.8Hz, H-10'a); 2.47 (2H, t, J, "2" = 7.4Hz, H1 "); 2.11 (2H, m, H-8 '); 1.92-1.85 (3H, m, H); -6'a, OH); 1.65 (3H, s, H-11 '); 1.58 (2H, q, J2 "-I ,, = 7.4Hz, H-2"); 1.39 (3H, s, H-6'a); 1.31-1.26

(6H, m, H-7 ', H-3 ", H-4"); 1.3 (3H, d, J6-5 = 4.4Hz, H-6); 1.10 (3H, s, H-6'p); 0.88 (3H, t, J5 "-4" = 6.6 Hz, H-5 ").

 13 C NMR (CDCl 3, 100MHz) δ (ppm): 158.1 (C-1 '); 154.8 (C-4'a); 142.9 (C-3 '); 133.4 (C-9 '); 125.5 (C-10 '); 110.9 (C-4 '); 110.8 (C-10 '); 110.6 (C-2 '); 100.2 (C-1); 77.8 (C-6 '); 73.4 (C-4); 72.3 (C-3); 71.4 (C-2); 71.3, 71.2, 70.6, 70.3 (4 * C-CH 2 O); 68.5 (C-5); 67.8 (C-CH 2 O); 66.9 (C-CH 2 O); 46.2 (C-6'a); 36.4 (C-1 "), 34.3 (C-10'a), 32 (C-7 '), 31.7 (C-2"); 31.3 (C-3 "); 28 (C-6'p); 25.5 (C-8 '); 23.9 (C-11'); 23 (C-4"); 19.6 (C-6'a); 18 (C-6); 14.5 (C-5 ").

MS (FAB + / NOBA) m / z: 615 [M + Na] +; 593 [M + H] +; 445 [M-sugar] +.

a-L-rhamnopyranoside de 17-(d9)-tétrahydrocannabinoyl-3,6,9,12,15-

α-Rhamnopyranoside of 17- (d9) -tetrahydrocannabinoyl-3,6,9,12,15-

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pentaoxaheptadecyl 21
Elution with a gradient of methanol (0-5%) in dichloromethane leads to 17- (9) -tetrahydrocannabinoyl-3,6,9,12,15-pentaoxaheptadecyl α-L-rhamnopyranoside 21 in the form of pale yellow sticky foam (Yield = 72%).

Rf 0.55 (CH2Cl2 / MeOH 97/3).

[?] D -115.2 (c = 1.05, CHCl3).

JIO-IOa.=1,8Hz, H-10') ; 4,85 (1H, d, JI-2=1,3Hz, H-l) ; 4,14 (2H, m, H-OCH2CfuOAr) ; 3,96-3,89 (3H, m, H- OCH2CH2O-Ar, H-5) ; 3,84-3,59 (24H, m, H-CH20, H-2, H-3, H-4) ; 3,18 (1H, dd, Joa-6 10,8Hz, J1Oa-io=l,8Hz, H-10'a) ; 2,91 (2H, m, OH) ; 2,62 (1H, m, OH) ; 2,47(2H, t, J1"-2"=7,7Hz, H-l") ; 2,11 (2H, m, H-8') ; 1,92-1,87 (3H, m, H-6'a) ; 1,68 (3H, s, H-ll') ; 1,57 (2H, q, J2"-1"=7,4Hz, H-2") ; 1,4 (3H, s, H-6'a) ; 1,36-1,24 (6H, m, H-7', H-3", H-4") ; (3H, d, J6-5=6,2Hz, H-6) ; 1,07 (3H, s, H-6'p) ; 0,88 (3H, t, J5"-4"=6,6Hz, H-5"). 1H NMR (CDCl3, 200MHz) δ (ppm): 6.32 (1H, s, H-4 '); 6.24 (1H, s, H-2 '); 6.14 (1H, d,

JI0-10a = 1.8 Hz, H-10 '); 4.85 (1H, d, JI-2 = 1.3Hz, H1); 4.14 (2H, m, H-OCH2CfuOAr); 3.96-3.89 (3H, m, H-OCH2CH2O-Ar, H-5); 3.84-3.59 (24H, m, H-CH 2 O, H-2, H-3, H-4); 3.18 (1H, dd, Joa-6 10.8Hz, J10a-10 = 1.8Hz, H-10'a); 2.91 (2H, m, OH); 2.62 (1H, m, OH); 2.47 (2H, t, J1 "-2" = 7.7 Hz, H1 "); 2.11 (2H, m, H-8 '); 1.92-1.87 (3H, m, H); 6'a), 1.68 (3H, s, H-11 '), 1.57 (2H, q, J2 "-1" = 7.4Hz, H-2 "); 1.4 (3H, s, H-6'a); 1.36-1.24 (6H, m, H-7 ', H-3 ", H-4"); (3H, d, J6-5 = 6.2 Hz, H-6); 1.07 (3H, s, H-6'p); 0.88 (3H, t, J5 "-4" = 6.6 Hz, H-5 ").

 13 C NMR (CDCl 3, 100MHz) (ppm): 157.9 (C-1 '); 154.8 (C-4'a); 142.9 (C-3 '); 133.4 (C-9 '); 125.5 (C-10 '); 110.9 (C-4 '); 110.8 (C-10 '); 104.3 (C-2 '); 100.4 (C-1); 77.4 (C-6 '); 73.5 (C-4); 72 (C-3); 71.1 (C-2); 71.70.9, 70.8, 70.6, 70.2 (7 ° C-CH 2 O); 68.5 (C-5); 67.7 (C-CH 2 O); 66.8 (C-CH 2 O); 46.2 (C-6'a); 36.4 (C-1 "), 34.3 (C-10'a), 32 (C-7 '), 31.7 (C-2"); 31.4 (C-3 "), 28.2 (C-6'p), 25.5 (C-8 '), 23.9 (Cl'), 23 (C-4"); 19.6 (C-6'a); 18 (C-6); 14.5 (C-5 ").

 MS (FAB + / NOBA) m / z: 747 [M + Na] +; 725 [M + H] +.

2,3,4-tri-O-acétyl-a-L-rhamnopyranoside de 17-citrylidène phloroglucinyl-
3,6,9,12,15-pentaoxaoctadécyle 22 2- Synthesis of Amphiphilic Glycoside 23 According to the Mitsunobu-type Reaction

2,3,4-tri-O-acetyl-α-L-rhamnopyranoside of 17-citrylidene phloroglucinyl-
3,6,9,12,15-pentaoxaoctadecyl 22

<Desc / Clms Page number 37>

Citrylidene phloroglucinol 16 (30 mg, 0.14 mmol), 2,3,9,12,15,18-hexaoxaoctadecyl 2,3,4-tri-Oacetyl-α-rhamnopyranoside 13 (227 mg, 0.46 mmol) and tributylphosphine (0.13 mL, 0.46 mmol) is dissolved in benzene (3 mL). The solution is then cooled to 0 ° C. and the azodicarbonyldipiperidine (136 mg, 0.46 mmol) is then added all at once. After 10 minutes at 0 ° C., a white precipitate appears and the medium is diluted with benzene (2 ml). The solution is then left stirring vigorously for 2 hours at room temperature.

After evaporation of the benzene, the residue obtained is chromatographed on a column of silica gel [eluent: gradient of acetone (0-2%) in ethyl ether] to yield compound 22 in the form of a colorless oil (Yield = 65%).

 Rf 0.85 (Et2O / acetone 98/2).

[a] D -33, 1 (c = 1.1, CHCl3).

3,92 (1H, dd, J5-4=9,7Hz, J5.6=6,4Hz, H-5) ; 3,84 (2H, m, H-OClhCH20Ar) ; 3,69- 3,64 (20H, m, H-CH20) ; 2,8 (1H, ddd, J9~8 -3,2Hz, J9-12=2,7Hz, J9~g=l,7Hz, H-9') ; 2,21 (1H, ddd, J8a.8p=13,3Hz, Jg ~9=3,2Hz, J8a~iOp=l,6Hz, H-8'a) ; 2,14-2,04 (6H, s, H-COCH3) ; 2,01 (1H, ddd, Ji2.np=ll,4Hz, Ji2-iia=5,lHz, J12-9=2,7Hz, H-12') ; 1,98 (3H, s, H-COCH3) ; 1,83 (1H, dd, J8 ~gR=13,2Hz, J8p~9=l,7Hz, H-8'P) ; 1,76 (1H, ddd, Jiop-ioa=13,5Hz, Jop~,la=5,7Hz, Jo~8 -3,lHz, H-10) ; 1,5 (3H, s, H-14') ; 1,45 (1H, dt, Jlo -top=13,5Hz, J1Oa-nP=13,3Hz, Joa~tl 5,3Hz, H-10'a) ; 1,39 (3H, s, H-16') ; 1,24 (1H, dt, J11 ~y=13,3Hz, Jila.ioa=5,3Hz, Jl,a~2=5,lHz, H-l l'a) ; 1,21 (3H, d, J6- 5=6,4Hz, H-6) ; 1 (3H, s, H-15') ; 0,63 (1H, dddd, JI~o 13,5Hz, Jlp~ty13,3Hz, Jla~12=11,4Hz, Jllp~loa=5,7Hz, H-11'[3). 1 H NMR (CDCl3,200MHz) # (ppm): 6.08 (2H, s, H-2 ', H-4'); 5.32 (1H, dd, J3-4 = 9.8Hz, J3.2 = 3.5Hz, H-3); 5.26 (1H, dd, J2-3 = 3.5Hz, J2-i = 1.7Hz, H-2); 5.05 (1H, dd, J4.5 = 9.6Hz, J4-3 = 9.6Hz, H-4); 4.76 (1H, s, H1); 4.04 (2H, m, H-OCH2CH2OAr);

3.92 (1H, dd, J5-4 = 9.7 Hz, J5.6 = 6.4 Hz, H-5); 3.84 (2H, m, H-OClhCH2OAr); 3.69- 3.64 (20H, m, H-CH 2 O); 2.8 (1H, ddd, J9 ~ 8 -3.2Hz, J9-12 = 2.7Hz, J9 ~ g = 1.7Hz, H-9 '); 2.21 (1H, ddd, J8a.8p = 13.3Hz, Jg-9 = 3.2Hz, J8a-iOp = 1.6Hz, H-8'a); 2.14-2.04 (6H, s, H-COCH3); 2.01 (1H, ddd, Ji2np = 11.4Hz, 1H2-1a = 5.1Hz, J12-9 = 2.7Hz, H-12 '); 1.98 (3H, s, H-COCH3); 1.83 (1H, dd, J8-gR = 13.2Hz, J8p-9 = 1.7Hz, H-8'P); 1.76 (1H, ddd, Jiop-ioa = 13.5Hz, Jop ~, la = 5.7Hz, J0 ~ 8 -3, 1Hz, H-10); 1.5 (3H, s, H-14 '); 1.45 (1H, dt, Jlo -top = 13.5Hz, J10a-nP = 13.3Hz, Joa ~ t1 5.3Hz, H-10'a); 1.39 (3H, s, H-16 '); 1.24 (1H, dt, J11 ~ y = 13.3Hz, Jila.ioa = 5.3Hz, J1, a ~ 2 = 5.1Hz, H1 a); 1.21 (3H, d, J6- 5 = 6.4Hz, H-6); 1 (3H, s, H-15 '); 0.63 (1H, dddd, JI ~ o 13.5Hz, Jlp ~ ty13,3Hz, Jla ~ 12 = 11.4Hz, Jllp ~ loa = 5.7Hz, H-11 '[3).

13 C NMR (CDCl 3, 50MHz) # (ppm): 170.169.9, 169.8 (3 ° C-COCH 3); 158.9 (C-3 '); 157.3 (C-5 '); 157 (C-1 '); 110 (C-6 '); 99.9 (C-1); 98 (C-4 '); 95.3 (C-2 '); 83.8 (C-7 '); 74.9 (C-13 '); 71.2 (C-4); 70.9 (C-3); 70.8 (C-2); 70.6, 70.5, 70.1, 69.7 (6 * CCH2O); 69.2 (C-5); 67.3.67, 66.3 (3 ° C-CH 2 O); 46.5 (C-12 '); 37.3 (C-10 '); 35.8 (C-8 '); 29.5 (C-14 '); 29 (C-16 '); 27.8 (C-19 '); 23.8 (C-15 '); 22.2 (C-11 '); 17.4 (C-6).

 MS (FAB + / NOBA) m / z: 819 [M + Na] +; 797 [M + H] +.

<Desc / Clms Page number 38>

a-L-rhamnopyranoside de 17-citrylidène phloroglucinyl-3,6,9,12,15- pentaoxaoctadécyle 23
Une solution du surfactant acétylé 22 (115mg, 0,11 mmole) et de méthanolate de sodium (71,3mg, 1,32 mmoles) dans du méthanol (3 ml) est laissée sous agitation à température ambiante pendant 4 heures. Après addition d'acide citrique en poudre jusqu'à neutralité, de la silice est ajoutée au milieu réactionnel qui est ensuite concentré sous pression réduite. Le résidu obtenu est chromatographié sur colonne de gel de silice [éluant: gradient de méthanol (0-10%) dans du dichlorométhane] pour conduire à l'a-L-rhamnopyranoside de 17-citrylidène phloroglucinyl-3,6,9,12,15-pentaoxaoctadécyle 23 sous la forme d'une mousse blanche collante (Rdt=75%).

17-Citrylidene phloroglucinyl-3,6,9,12,15-pentaoxaoctadecyl aL-rhamnopyranoside 23
A solution of the acetylated surfactant (115mg, 0.11mmol) and sodium methanolate (71.3mg, 1.32mmol) in methanol (3ml) was stirred at room temperature for 4 hours. After adding citric acid powder to neutrality, silica is added to the reaction medium which is then concentrated under reduced pressure. The residue obtained is chromatographed on a column of silica gel [eluent: gradient of methanol (0-10%) in dichloromethane] to give a-L-rhamnopyranoside of 17-citrylidene phloroglucinyl-3,6,9,12 15-pentaoxaoctadecyl 23 in the form of a tacky white foam (yield = 75%).

 Rf 0.52 (CH 2 Cl 2 / MeOH 95/5).

 [?] D-28.6 (c = 1, CHCl3).

1) ; 4,06 (2H, m, H-OCH2CfuO-Ar) ; 3,96 (1H, m, H-5) ; 3,82 (2H, m, HOCfuCH20-Ar) ; 3,75-3,6 (23H, m, H-CH20, H-2, H-3, H-4) ; 3,22 (2H, m, OH) ; 2,99 (1H, m, OH) ; 2,81 (1H, ddd, J9~8 =3,2Hz, J9-12=2,7Hz, J9~ga=l,7Hz, H-9') ; 2,21 (1H, ddd, J8 ~8a=13,3Hz, Jg.-9=3,2Hz, J8 ~o=l,6Hz, H-8'a) ; 2,01 (1H, ddd, J12~lp=11,4Hz, J12-y5,lHz, J12-9=2,7Hz, H-12') ; 1,83 (1H, dd, J8a.8p=13,2Hz, J813- 9=l,7Hz, H-8'p) ; 1,76 (1H, ddd, J,op-ioa=13,5Hz, Jloa-ly=5,7Hz, Jloa~s 3,lHz, H- 10'p) ; 1,51 (3H, s, H-14') ; 1,45 (1H, dt, JlOa-IOI3=13,5Hz, Jio,-Ilp=13,3Hz, 310 - 11 5,3Hz, H-10'a) ; 1,36 (3H, s, H-16') ; 1,32 (3H, d, J6-5=6,lHz, H-6) ; 1,23 (1H, dt, Jn -1y=13,3Hz, Ju -to 5,3Hz, J,ia-12=5,lHz, H-ll'a) ; 1,01 (3H, s, H-15') ; 0,63 (1H, dddd, Jlp~to 13,5Hz, J a~11 13,3Hz, JItR~2=11,4Hz, J1R-ioa=5,7Hz, H-11 '). 1 H NMR (CDCl 3, 250MHz) δ (ppm): 6.1 (2H, s, H-2 ', H-4'); 4.85 (1H, d, JI-2 = 1.5Hz, H-

1); 4.06 (2H, m, H-OCH2CfuO-Ar); 3.96 (1H, m, H-5); 3.82 (2H, m, HOCfuCH 2 O-Ar); 3.75-3.6 (23H, m, H-CH 2 O, H-2, H-3, H-4); 3.22 (2H, m, OH); 2.99 (1H, m, OH); 2.81 (1H, ddd, J9 ~ 8 = 3.2Hz, J9-12 = 2.7Hz, J9 ~ ga = 1.7Hz, H-9 '); 2.21 (1H, ddd, J8 ~ 8a = 13.3Hz, Jg-9 = 3.2Hz, J8 ~ o = 1.6Hz, H-8'a); 2.01 (1H, ddd, J12 ~ 1p = 11.4Hz, J12-y5, 1Hz, J12-9 = 2.7Hz, H-12 '); 1.83 (1H, dd, J8a.8p = 13.2Hz, J813-9 = 1.7Hz, H-8'p); 1.76 (1H, ddd, J, op-ioa = 13.5Hz, Jloa-ly = 5.7Hz, Jloa ~ s 3, 1Hz, H-10'p); 1.51 (3H, s, H-14 '); 1.45 (1H, dt, J10a-1013 = 13.5Hz, J1, -I1p = 13.3Hz, 310- 5.3Hz, H-10'a); 1.36 (3H, s, H-16 '); 1.32 (3H, d, J6-5 = 6, 1Hz, H-6); 1.23 (1H, dt, Jn -1y = 13.3Hz, Ju -to 5.3Hz, J, ia-12 = 5.1Hz, H-11a); 1.01 (3H, s, H-15 '); 0.63 (1H, dddd, Jlp ~ 13.5Hz, J a ~ 11 13.3Hz, JItR ~ 2 = 11.4Hz, J1R-10a = 5.7Hz, H-11 ').

13 C NMR (CDCl3 · 100MHz) δ (ppm): 158.8 (C-3 '); 157.6 (C-5 '); 157.1 (C-1 '); 109.6 (C-6 '); 99.9 (C-1); 97.8 (C-4 '); 95.6 (C-2 '); 84.1 (C-7 '); 74.8 (C-13 '); 73.1 (C-4); 71.7 (C-3); 70.8 (C-2); 70.7, 70.5, 70.4, 70.2, 69.7 (6 ° C-CH 2 O); 68 (C-5); 67.5 (C-

<Desc / Clms Page number 39>

 CH20); 66.5 (C-CH 2 O); 46.7 (C-12 '); 37.3 (C-10 '); 35.3 (C-8 '); 29.7 (C-14 '); 29 (C-16 '); 27.8 (C-9 '); 23.7 (C-15 '); 22 (C-11 '); 17.6 (C-6).

 MS (FAB + / NOBA) m / z: 693 [M + Na] +; 260 [M-sugar-TEG] +.

2,3,4-tri-O-acétyl-a-L-rhamnopyranoside de 3,6,8-trioxanonanyle 24
A une solution du compose 6 (538mg, 1,5 mmoles) et de tri (éthylèneglycol) (0,26ml, 1,96 mmoles) dissous dans du dichlorométhane anhydre (12 ml) est additionné goutte à goutte l'éthérate de trifluorure de bore (1,28 ml, 10 mmoles). Le mélange réactionnel est laissé sous agitation à température ambiante pendant 4 heures. Il est ensuite lavé avec une solution aqueuse saturée d'hydrogénocarbonate de sodium. La phase organique est séchée sur du sulfate de sodium anhydre puis concentrée sous vide. Le résidu obtenu est chromatographié sur colonne de gel de silice [éluant : dichlorométhane] pour conduire au composé 24 sous forme d'huile incolore (Rdt=81%). E / Synthesis of Amphiphilic Glycosides 28, 29 and 30 Having a Lipophilic Part of the Retinoid and Acyl Type

3,6,4-trioxanonanyl 2,3,4-tri-O-acetyl-α-rhamnopyranoside 24
To a solution of the compound 6 (538 mg, 1.5 mmol) and tri (ethylene glycol) (0.26 ml, 1.96 mmol) dissolved in anhydrous dichloromethane (12 ml) is added dropwise the trifluoride etherate. boron (1.28 ml, 10 mmol). The reaction mixture is stirred at room temperature for 4 hours. It is then washed with a saturated aqueous solution of sodium hydrogencarbonate. The organic phase is dried over anhydrous sodium sulphate and then concentrated in vacuo. The residue obtained is chromatographed on a column of silica gel [eluent: dichloromethane] to yield compound 24 in the form of a colorless oil (yield = 81%).

 Rf 0.52 (CH 2 Cl 2 / MeOH 95/5).

(3H, d, J6-5=6,l Hz, H-6). [?] D -38.2 (c = 1.03, CHCl3) - 1H NMR (CDCl3, 250MHz)
3 (ppm): 5.29 (1H, dd, J3-4 = 9.8Hz, J3-2 = 3.5Hz, H-3), 5.24 (1H, dd, J2-3 = 3.5Hz, J2-1 = 1.7 Hz, H-2); 5.06 (1H, dd, J4-5 = 9.8Hz, J4-3 = 9.8Hz, H-4); 4.79 (1H, d, J1-2 = 1.5Hz, H1); 3.93 (1H, dd, Js-4 = 9.8 Hz, J5.6 = 6.3 Hz, H-5); 3.78-3.59 (12H, m, H-CH 2 O); 2.44 (1H, t, J = 6Hz, OH); (9H, s, H-COCH3);

(3H, d, J6-5 = 6, 1 Hz, H-6).

 13 C NMR (CDCl 3, 50MHz) # (ppm): 170.2, 170.1, 169.9 (3 ° C-COCH 3); 97.6 (C-1); 72.6 (C-4); 71.1 (C-3); 70.8 (C-2); 70.4, 70.1, 69.9 (3 ° C-CH 2 O); 69.1 (C-5); 67.1 (C-CH 2 O); 66.4 (C-CH 2 O); 61.8 (C-CH 2 OH); 20.9.20.8, 20.7 (3 ° C-COCH 3); 17.4 (C-6).

 MS (FAB + / NOBA)

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 m / z: 445 [M + Na] +; 423 [M + H] +; 273 [M-TEG] +.

trioxanonanyle 24 (1 mmole), l'acide rétinoïque ou l'acide 2-trans-(3-ionylidène acétique ou l'acide palmitique (1 mmole) et la 4-diméthylaminopyridine (1,2 mmoles) sont dissous dans une quantité minimum de dichlorométhane anhydre. A cette solution

refroidie à 0 C, du chlorhydrate de N-(3-diméthylaminopropyl)-N-éthylcarbodiimide (1,2 mmoles), dissous dans un minimum de dichlorométhane anhydre, est additionné goutte à goutte. Après une nuit à température ambiante, le mélange réactionnel est lavé avec de l'eau, avec une solution aqueuse d'acide citrique à 5% puis avec de l'eau. Les phases organiques sont alors séchées sur du sulfate de sodium anhydre et concentrées sous vide. Le résidu obtenu est à chaque fois purifié par chromatographie sur colonne de gel de silice. Les conditions d'élution et le rendement de chaque composé sont donnés ci-après.

F / General procedure for the synthesis of acetylated amphiphilic glycosides 25, 26 and 27
2,3,4-tri-O-acetyl-α-L-rhamnopyranoside of 3,6,8-

trioxanonanyl 24 (1 mmol), retinoic acid or 2-trans- (3-ionylidene acetic acid or palmitic acid (1 mmol) and 4-dimethylaminopyridine (1.2 mmol) are dissolved in a minimum amount anhydrous dichloromethane.

cooled to 0 ° C., N- (3-dimethylaminopropyl) -N-ethylcarbodiimide hydrochloride (1.2 mmol), dissolved in a minimum of anhydrous dichloromethane, is added dropwise. After one night at room temperature, the reaction mixture is washed with water, with a 5% aqueous solution of citric acid and then with water. The organic phases are then dried over anhydrous sodium sulphate and concentrated in vacuo. The residue obtained is each time purified by column chromatography on silica gel. The elution conditions and the yield of each compound are given below.

8-Retinoyl-3,6,8-trioxanonanyl 2,3,4-tri-O-acetyl-α-aminopyranoside
Elution with a gradient of methanol (0-1%) in dichloromethane leads to the production of 8-retinoyl-3,6,8-trioxanonanyl 2,3,4-tri-O-acetyl-α-rhamnopyranoside In the form of a yellow oil (Yield = 91%, all-trans / 13'-cis isomers 54/46).

 Rf 0.8 (CH2Cl2 / MeOH 94/6).

 [α] D 42.2 (c = 1.1, CHCl 3).

Jl~lz=14,9Hz, Jl-o=1l,SHz, H-1 l') ; 6,34-6,11 (4H, m, H-12', H-7', H-8', H-10') ; 5,84 (1H, s, H-14') ; 5,37-5,27 (2H, m, H-2, H-3) ; 5,08 (1H, dd, J4-5=9,7Hz, J4-3=9,7Hz, H-4) ; 4,8 (1H, d, 31~2=l,4Hz, H-1) ; 4,32-4,27 (2H, m, H-OCH2CH OCO) ; 3,99-3,63 (11H, m, H-5, H-CH20) ; 2,37 (3H, d, J16-14=lHz, H-16') ; 2,17 (3H, s, H- COCH3) ; 2,09 (3H, d, J17-10=1,2Hz, H-17') ; 2,05-2 (1H, m, H-4') ; (6H, s, H- 1H NMR (CDCl3, 250MHz) all-trans isomer: # (ppm): 7.09-6.94 (1H, dd,

J1 = 14.9 Hz, J1-O = 11, SHz, H-1); 6.34-6.11 (4H, m, H-12 ', H-7', H-8 ', H-10'); 5.84 (1H, s, H-14 '); 5.37-5.27 (2H, m, H-2, H-3); 5.08 (1H, dd, J4-5 = 9.7 Hz, J4-3 = 9.7 Hz, H-4); 4.8 (1H, d, 31-2 = 1.4Hz, H-1); 4.32-4.27 (2H, m, H-OCH2CHCO); 3.99-3.63 (11H, m, H-5, H-CH 2 O); 2.37 (3H, d, J16-14 = 1Hz, H-16 '); 2.17 (3H, s, H-COCH3); 2.09 (3H, d, J17-10 = 1.2Hz, H-17 '); 2.05-2 (1H, m, H-4 '); (6H, s, H-

<Desc / Clms Page number 41>

isomère 13'-cis : ô (ppm) : 7,79 (1H, d, J12~I≥I5,4Hz, H- 12') ; 7,09-6,94 (1H, dd, J1>>~2=15,3Hz, J1>>~IO=11,7Hz, H-11') ; 6,34-6,11 (3H, m, H-7', H-8', H-10') ; 5,71(1H, s, H-14') ; 5,37-5,27 (2H, m, H-2, H-3) ; 5,08(1H, dd, J4-5=9,7Hz, J4-3=9,7Hz, H-4) ; 4,8 (1H, d, JI-2=1,4Hz, H-1) ; 4,32-4,27 (2H, m, H-

OCH2CH OCO) ; 3,99-3,63 (11H, m, H-5, H-CH20) ; 2,37 (3H, d, J16.14=lHz, H-16') ; 2,17 (3H, s, H-COCH3) ; 2,09 (3H, d, Jn-io=l,2Hz, H-17') ; 2,05-2 (1H, m, H-4') ; 2 (6H, s, H-COCH3) ; 1,7-1,58 (5H, m, H-18', H-3') ; 1,52-1,46 (2H, m, H-2') ; 1,24(3H, d, J6-5=6,3Hz, H-6) ; 1,05 (3H, s, H-19') ; 1,04 (3H, s, H-20'). COCH3); 1.7-1.58 (5H, m, H-18 ', H-3'); 1.52-1.46 (2H, m, H-2 '); (3H, d, J6-5 = 6.3 Hz, H-6); 1.05 (3H, s, H-19 '); 1.04 (3H, s, H-20 ').

13'-cis isomer: δ (ppm): 7.79 (1H, d, J12 ~ 1≥I5.4Hz, H-12 '); 7.09-6.94 (1H, dd, J1 >> -2 = 15.3Hz, J1 >> -10 = 11.7Hz, H-11 '); 6.34-6.11 (3H, m, H-7 ', H-8', H-10 '); 5.71 (1H, s, H-14 '); 5.37-5.27 (2H, m, H-2, H-3); 5.08 (1H, dd, J4-5 = 9.7 Hz, J4-3 = 9.7 Hz, H-4); 4.8 (1H, d, JI-2 = 1.4Hz, H-1); 4.32-4.27 (2H, m, H-

OCH2CH OCO); 3.99-3.63 (11H, m, H-5, H-CH 2 O); 2.37 (3H, d, J16.14 = 1Hz, H-16 '); 2.17 (3H, s, H-COCH3); 2.09 (3H, d, Jn-10 = 1,2 Hz, H-17 '); 2.05-2 (1H, m, H-4 '); 2 (6H, s, H-COCH3); 1.7-1.58 (5H, m, H-18 ', H-3'); 1.52-1.46 (2H, m, H-2 '); 1.24 (3H, d, J6-5 = 6.3 Hz, H-6); 1.05 (3H, s, H-19 '); 1.04 (3H, s, H-20 ').

69,1 (C-5) ; 53,5 (C-OCHZÇH20C0) ; 39,6 (C-OCH2CH20CO); 34,2 (C-l') ; 34 (C- 4') ; 33(C-16', C-17') ; 21,7 (C-18') ; 20,9,20,8, 20,7 (3*C-COCH3) ; 19,2 (C-3') ; 17,5 (C-6) ; 13,8 (C-20') ; 12,8 (C-19'). isomère 13'-cis : # (ppm) : 170,2, 170,1, 169,9 (3*C-COCH3) ; 166,2 (C-15') ; 151,8 (C-13') ; 139,9 (C-9') ; 137,6 (C-6') ; 137,3 (C-8') ; 134,9 (C- 12') ; 131,2 (C-10') ; 130,2 (C-I1') ; 129,7 (C-7') ; 128,7 (C-5') ; 118 (C-14') ; 97,6 (C-1) ; 72,6 (C-4) ; 71,1 (C-3) ; 70,8 (C-2) ; 70,4,70,3, 70,1,69,2 (4*C-CH20) ; 69,1

(C-5) ; 53,5 (C-OCH2CH20CO); 39,6 (C-OCH2ÇHZOCO) ; 34,2 (C-l') ; 34 (C-4') ; 33 (C-16', C-17') ; 21,7 (C-18') ; 20,9,20,8, 20,7 (3*C-COCH3) ; 19,2 (C-3') ; 17,5 (C-6) , 13,8 (C-20') ; 12,8 (C-19'). 13C NMR (CDCl3, 50MHz) all-trans isomer: # (ppm): 170.2, 170.1, 169.9 (3 ° CCOCH3); 167 (C-15 '); 153.3 (C-13 '); 139.7 (C-9 '); 137.6 (C-6 '); 137.2 (C-8 '); 134.9 (C-12 '); 131.2 (C-10 '); 130 (C-11 '); 129.7 (C-7 '); 128.7 (C-5 '); 118 (C-14 '); 97.6 (C-1); 72.6 (C-4); 71.1 (C-3); 70.8 (C-2); 70.4, 70.3, 70.1, 69.2 (4 * C-CH 2 O);

69.1 (C-5); 53.5 (C, OCH 2 CH 2 OCO); 39.6 (C-OCH2CH2OCO); 34.2 (C-1 '); 34 (C-4 '); 33 (C-16 ', C-17'); 21.7 (C-18 '); 20.9.20.8, 20.7 (3 ° C-COCH 3); 19.2 (C-3 '); 17.5 (C-6); 13.8 (C-20 '); 12.8 (C-19 '). 13'-cis isomer: # (ppm): 170.2, 170.1, 169.9 (3 * C-COCH3); 166.2 (C-15 '); 151.8 (C-13 '); 139.9 (C-9 '); 137.6 (C-6 '); 137.3 (C-8 '); 134.9 (C-12 '); 131.2 (C-10 '); 130.2 (C-11); 129.7 (C-7 '); 128.7 (C-5 '); 118 (C-14 '); 97.6 (C-1); 72.6 (C-4); 71.1 (C-3); 70.8 (C-2); 70.4, 70.3, 70.1, 69.2 (4 * C-CH 2 O); 69.1

(C-5); 53.5 (C-OCH2CH2OCO); 39.6 (C-OCH 2 CH 2 O); 34.2 (C-1 '); 34 (C-4 '); 33 (C-16 ', C-17'); 21.7 (C-18 '); 20.9.20.8, 20.7 (3 ° C-COCH 3); 19.2 (C-3 '); 17.5 (C-6), 13.8 (C-20 '); 12.8 (C-19 ').

MS (FAB + / NOBA) m / z: 705 [M + H] +; 273 [M-sugar] +.

8- (3-Ionylidene acetyl-3,6,8-trioxanonanyl) 2,3,4-tri-O-acetyl-α-L-rhamnopyranoside 26

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Elution with a gradient of methanol (0-1%) in dichloromethane leads to the production of 2,3,4-tri-O-acetyl-α-L-rhamnopyranoside of 8-ionylidene-3,6,8-acetylidene -trioxanonanyl 26 as a yellow oil (Yield = 52%, all-trans / 9'-cis isomers 56/44).

 Rf 0.9 (CH 2 Cl 2 / MeOH 95/5).

 [?] D -40.9 (c = 1, CHCl3).

isomère 9'-cis : ô (ppm) : 7,63 (1H, d, J7'-S'=16,5Hz, H-7') ; 6,57 (1H, d, J8'-7'=16,5Hz, H-8') ; 5,68 (1H, s, H-10') ; 5,34-5,24 (2H, m, H-2, H-3) ; 5,08 (1H, dd, J4-5=9,7Hz, J4-3=9,7Hz, H-4) ; 4,77 (1H, d, Ji.2=l,3Hz, H-1) ; 4,29-4,22 (2H, m, H-OCH2CH20CO) ; 3,92 (1H, dd, J5-4=9,6Hz, J5-6=6,3Hz, H-5) ; 3,80-3,58

(10H, m, H-CH20) ; 2,37 (3H, d, J,5-1o=l,lHz, H-15') ; 2,14-1,97 (9H, s, H-COCH3) ; 1,97 (2H, m, H-4') ; (3H, s, H-14') ; 1,64-1,55 (2H, m, H-3') ; (2H, m, H-2') ; 1,21 (3H, d, J6-5=6,4Hz, H-6) ; 1,05 (3H, s, H-12') ; 1,01 (3H, s, H-13'). 1H NMR (CDCl 3, 200MHz) all-trans isomer: # (ppm): 6.57 (1H, d, J = 7 '= 16.5Hz, H-8'); 6.08 (1H, d, J7'-8 '= 16.5Hz, H-7'); 5.78 (1H, s, H-10 '); 5.34-5.24 (2H, m, H-2, H-3); 5.08 (1H, dd, J4.5 = 9.7 Hz, J4-3 = 9.7 Hz, H-4); 4.77 (1H, d, JI-2 = 1.3 Hz, H-1); 4.29- 4.22 (2H, m, H-OCH2CH2CO3); 3.92 (1H, dd, J5-4 = 9.6Hz, J5.6 = 6.3Hz, H-5); 3.80- 3.58 (10H, m, H-CH 2 O); 2.37 (3H, d, J15-10 = 1.1Hz, H-15 '); 2.14-1.97 (9H, s, H-COCH3); 1.97 (2H, m, H-4 '); (3H, s, H-14 '); (2H, m, H-3 '); 1.43 (2H, m, H-2 '); (3H, d, J6-5 = 6.4Hz, H-6); 1.05 (3H, s, H-12 '); (3H, s, H-13 ').

9'-cis isomer: δ (ppm): 7.63 (1H, d, J7'-S '= 16.5Hz, H-7'); 6.57 (1H, d, J8'-7 '= 16.5Hz, H-8'); 5.68 (1H, s, H-10 '); 5.34-5.24 (2H, m, H-2, H-3); 5.08 (1H, dd, J4-5 = 9.7 Hz, J4-3 = 9.7 Hz, H-4); 4.77 (1H, d, J1.2 = 1.3 Hz, H-1); 4.29-4.22 (2H, m, H-OCH2CH2CO3); 3.92 (1H, dd, J5-4 = 9.6Hz, J5-6 = 6.3Hz, H-5); 3.80 to 3.58

(10H, m, H-CH 2 O); 2.37 (3H, d, J, 5-1 0 = 1.1 Hz, H-15 '); 2.14-1.97 (9H, s, H-COCH3); 1.97 (2H, m, H-4 '); (3H, s, H-14 '); 1.64-1.55 (2H, m, H-3 '); (2H, m, H-2 '); 1.21 (3H, d, J6-5 = 6.4Hz, H-6); 1.05 (3H, s, H-12 '); 1.01 (3H, s, H-13 ').

 13C NMR (CDCl3,100MHz) all-trans isomer: # (ppm): 170.2, 170.1, 169.9 (3 * CCOCH3); 167.6 (C-11 '); 154 (C-9 '); 137.5 (C-6 '); 135.4 (C-8 '); 134.4 (C-7 '); 130.2 (C-5 '); 116 (C-10 '); 97.6 (C-1); 72.6 (C-4); 71.1 (C-3); 70.8 (C-2); 70.4, 70.3, 70.1, 69.2 (4 * C-CH 2 O); 69.1 (C-5); 66.5 (C-CH 2 O); 66.8 (C-CH 2 O); 39.8 (C-1 '); 34.6 (C-4 '); 29.4 (C-12 '); 29.3 (C-13 '); 22.1 (C-14 '); 20.9.20.8, 20.7 (3 ° C-CHCH3); 19.5 (C-3 '); 17.5 (C-6); 14.1 (C-15 '). 9'-cis isomer: # (ppm): 170.2, 170.1, 169.9 (3 * C-CHO3); 166.7 (C-11 '); 152.7 (C-9 '); 137.6 (C-6 '); 136.5 (C-8 '); 132.7 (C-7 '); 129.8 (C-5 '); 118 (C-10 '); 97.6 (C-1); 72.6 (C-4); 71.1 (C-3); 70.8 (C-2); 70.4, 70.3, 70.1, 69.2 (4 * C-CH 2 O); 69.1 (C-5); 66.8 (C-CH 2 O); 66.5 (C-CH 2 O); 40.2 (C-1 '); 34.5 (C-4 '); 29.4 (C-12 '); 29.3 (C-13 '); 22.2 (C-14 '); 20.9, 20.8, 20.7 (3 ° C-COCH3); 19.5 (C-3 '); 17.5 (C-6), 14.1 (C-15 ').

 MS (FAB + / NOBA)

<Desc / Clms Page number 43>

m / z: 661 [M + Na] +; 639 [M + H] +; 273 [M-sugar] +.

2,3,4-tri-O-acétyl-a-L-rhamnopyrnoside de 8-palmitoyl-3,6,8-trioxanonanyle 27
L'élution par un gradient de méthanol (0-3%) dans du dichlorométhane conduit à l'obtention du 2,3,4-tri-O-acétyl-a-L-rhamnopyranoside de 8-palmitoyl-3,6,8-trioxanonanyle 27 sous forme d'une huile incolore (Rdt=42%).

8-Palmitoyl-3,6,8-trioxanonanyl 2,3,4-tri-O-acetyl-α-Lhamnopyrnoside 27
Elution with a gradient of methanol (0-3%) in dichloromethane leads to the production of 8-palmitoyl-3,6,8-trioxanonanyl 2,3,4-tri-O-acetyl-α-rhamnopyranoside 27 as a colorless oil (Yield = 42%).

 Rf 0.8 (CH 2 Cl 2 / MeOH 9/1).

 [?] D -36.8 (c = 1.06, CHCl3).

OCH2CH90CO) ; 3,87 (1H, dd, JS.=9,6Hz, J5.6=6,3Hz, H-5) ; 3,73-3,66 (IOH, m, H- CH20) ; 2,33 (2H, t, J2'-3'=7,6Hz, H-2') ; 2,14-1,98 (9H, s, H-COCH3) ; (2H, m,

H-3') ; 1,25-1,20 (27H, m, H-6, H-4'-H-15') ; 0,88 (3H, t, J,6,-15,=6,4Hz, H-13'). 1 H NMR (CDCl 3, 200MHz) δ (ppm): 5.32-5.26 (2H, m, H-2, H-3); 5.06 (1H, dd, J4-s = 9.6Hz, J4-3 = 9.6Hz, H-4); 4.78 (1H, s, H1); 4.26-4.20 (2H, m, H-

OCH2CH90CO); 3.87 (1H, dd, JS = 9.6Hz, J5.6 = 6.3Hz, H-5); 3.73-3.66 (OHI, m, H-CH 2 O); 2.33 (2H, t, J2'-3 '= 7.6 Hz, H-2'); 2.14-1.98 (9H, s, H-COCH3); (2H, m,

H-3 '); 1.25-1.20 (27H, m, H-6, H-4'-H-15 '); 0.88 (3H, t, J, 6, -15, = 6.4Hz, H-13 ').

(C-5) ; 67,5, 66,7, 63,7 (3*C-CH20) ; 53,8 (C-OCHlCH20CO) ; 34,6 (C-2') ; 32,3 (C- 3') ; 30,1 (C-4', C-5') ; 30 (C-6', C-7', C-8', C-9') ; 29,9 (C-10') ; 29,8 (C-1 l') ; 29,7 (C-12') ; 29,6 (C-13') ; 25,3 (C-14') ; 23,1 (C-15') ; 21,3,21,2, 21,1 (3*C-COCH3) ; 17,8 (C-6); 14,5 (C-16'). 13 C NMR (CDCl 3, 100MHz) δ (ppm): 174.3 (C-1 '); 170.6, 170.5, 170.4 (3 ° C-COCH3); 98 (C-1); 71.5 (C-4); 71.2 (C-3); 71 (C-2); 70.5 (C-CH 2 O); 69.6 (C-CH 2 O); 69.4

(C-5); 67.5, 66.7, 63.7 (3 ° C-CH 2 O); 53.8 (C-OCHlCH2CO3); 34.6 (C-2 '); 32.3 (C-3 '); 30.1 (C-4 ', C-5'); (C-6 ', C-7', C-8 ', C-9'); 29.9 (C-10 '); 29.8 (C-1 1 '); 29.7 (C-12 '); 29.6 (C-13 '); 25.3 (C-14 '); 23.1 (C-15 '); 21.3, 21.2, 21.1 (3 * C-COCH3); 17.8 (C-6); 14.5 (C-16 ').

 MS (ESI + / 30eV) m / z: 683 [M + Na] +.

 G / General Procedure for Synthesis of Amphiphilic Glycosides 28, 29 and 30: glycosides.

 The peracetylated glycoside is dissolved in a solution of methanol saturated with ammonia (25 ml / mmol of glycoside). The reaction mixture is left at 4 ° C. overnight. After evaporation of the methanol, the residue obtained is each time purified by column chromatography on silica gel. Elution conditions

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a-L-rhamnopyranoside de 8-rétinoyl-3,6,8-trioxanonanyle 28
L'élution par un gradient de méthanol (0-3%) dans du dichlorométhane conduit à l'obtention de l'a-L-rhamnopyranoside de 8-rétinoyl- 3,6,8-trioxanonanyle 28 sous forme d'une huile jaune (Rdt=90%, isomères tout- trans/13'-cis 70/30). and the yield of each compound are given below.

8-Retinoyl-3,6,8-trioxanonanyl a-rhamnopyranoside 28
Elution with a gradient of methanol (0-3%) in dichloromethane leads to obtaining 8-retinoyl-3,6,8-trioxanonanyl a-L-rhamnopyranoside 28 in the form of a yellow oil. (Yield = 90%, all-trans isomers / 13'-cis 70/30).

 Rf 0.4 (CH 2 Cl 2 / MeOH 95/5).

 [?] D -30.7 (c = 1, CHCl3).

isomère tout-trans : 8 (ppm) : 7,04 (1H, dd, J,1>~lz≥lSHz, Jii,-Io,=l 1,6Hz, H-ll') ; 6,35-6,11 (4H, m, H-12', H-7', H-8', H-10') ; 5,84 (1H, s, H- 14') ; 5,48 (1H, m, OH) ; 4,85(1H, d, J1-2=1,2Hz, H-l) ; 4,31 (2H, m, HOCH2CH2OCO) : 3,99 (1H, m, H-4) ; 3,86-3,63(14H, m, H-5, H-2, H-3, H-CH20,

OH) ; 2,89 (1H, m, OH) ; 2,37 (3H, d, J]6'-14,=0,9Hz, H-16') ; 2,1 (3H, d, J1>~ 10'=1,1Hz, H-17') ; 2,04-2 (1H, m, H-4') ; (3H, s, H-18') ; 1,67-1,61 (5H, m, H- 3') ; 1,52-1,46 (2H, m, H-2') ; (3H, d, J6-5=6,2Hz, H-6) ; 1,05 (6H, s, H-20', H- 19').

isomère 13'-cis : 8 (ppm): 7,77 (1H, d, J2>~1>≥15,SHz, H- 12') ; 7,02 (in, dd, JI1'-12,=15,2Hz, JnM0≥ll,7Hz, H-ll') ; 6,35-6,11 (3H, m, H-7', H-8', H-10') ; 5,71 (1H, s, H-14') ; 5,48 (1H, m, OH) ; 4,85 (1H, d, JI-2=1,2Hz, H-1) ; 4,31 (2H, m, H-OCH2CH20CO) ; 3,99 (1H, m, H-4) ; 3,86-3,63(14H, m, H-5, H-2,

H-3, H-CH20, OH) ; 2,89 (1H, m, OH) ; 2,37 (3H, d, Jl6'-14,=0,9Hz, H-16') ; 2,1 (3H, d, J17'-lo,=l,IHz, H-17') ; 2,04-2 (1H, m, H-4') ; 1,74 (3H, s, H-18') ; 1,67-1,61 (5H, m, H-3') ; 1,52-1,46 (2H, m, H-2') ; 1,34 (3H, d, J6-5=6,2Hz, H-6) ; 1,05 (6H, s, H- 20', H-19'). 1H NMR (CDCb, 250MHz)

all-trans isomer: 8 (ppm): 7.04 (1H, dd, J, 1Hz-1Hz, 1H, -Io, 1.6Hz, H-11 '); 6.35-6.11 (4H, m, H-12 ', H-7', H-8 ', H-10'); 5.84 (1H, s, H-14 '); 5.48 (1H, m, OH); 4.85 (1H, d, J1-2 = 1.2Hz, H1); 4.31 (2H, m, HOCH2CH2OCO): 3.99 (1H, m, H-4); 3.86-3.63 (14H, m, H-5, H-2, H-3, H-CH 2 O,

OH) ; 2.89 (1H, m, OH); 2.37 (3H, d, J] 6'-14, = 0.9 Hz, H-16 '); 2.1 (3H, d, J1> ~ 10 '= 1.1Hz, H-17'); 2.04-2 (1H, m, H-4 '); (3H, s, H-18 '); 1.67-1.61 (5H, m, H-3 '); 1.52-1.46 (2H, m, H-2 '); (3H, d, J6-5 = 6.2 Hz, H-6); 1.05 (6H, s, H-20 ', H-19').

13'-cis isomer: δ (ppm): 7.77 (1H, d, J2>-1> ≥15, SHz, H-12 '); 7.02 (in, dd, JI1'-12, = 15.2Hz, JnM0≥11, 7Hz, H-11 '); 6.35-6.11 (3H, m, H-7 ', H-8', H-10 '); 5.71 (1H, s, H-14 '); 5.48 (1H, m, OH); 4.85 (1H, d, JI-2 = 1.2 Hz, H-1); 4.31 (2H, m, H-OCH2CH2CO3); 3.99 (1H, m, H-4); 3.86-3.63 (14H, m, H-5, H-2,

H-3, H-CH 2 O, OH); 2.89 (1H, m, OH); 2.37 (3H, d, J16'-14, = 0.9 Hz, H-16 '); 2.1 (3H, d, J17'-lo, = 1, 1Hz, H-17 '); 2.04-2 (1H, m, H-4 '); 1.74 (3H, s, H-18 '); 1.67-1.61 (5H, m, H-3 '); 1.52-1.46 (2H, m, H-2 '); 1.34 (3H, d, J6-5 = 6.2 Hz, H-6); 1.05 (6H, s, H-20 ', H-19').

 13 C NMR (CDCl 3, 50MHz) all-trans isomer: 8 (ppm): 167 (C-15 '); 153.3 (C-13 '); 139.7 (C-9 '); 137.6 (C-6 '); 137.2 (C-8 '); 134.9 (C-12 '); 131.2 (C-10 '); 130 (C-11 '); 129.7 (C-7 '); 128.7 (C-5 '); 118 (C-14 '); 99.9 (C-1); 72.7 (C-4); 71.5 (C-3); 70.8

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(C-2) ; 70,4, 70,3, 70,1, 69,2 (4*C-CH20) ; 68,2 (C-5) ; 53,5 (C-OCH2ÇH20C0) ; 39,6 (C-OCH2CH20CO) ; 34,2 (C-l') ; 34 (C-4') ; 33 (C-16', C-17') ; (C-18') ; 19,2 (C-3') ; 17,5 (C-6) ; 13,8 (C-20') ; 12,8 (C-19'). isomère 13'-cis : # (ppm): 166,2 (C-15') ; 151,8 (C-13') ; 139,9 (C-9') ; 137,6 (C-6') ; 137,3 (C-8') ; 134,9 (C-12') ; 131,2 (C-10') ; 130,2 (C- Il') ; 129,7 (C-7') ; 128,7 (C-5') ; 118 (C-14') ; 99,9 (C-1) ; 72,7 (C-4) ; 71,5 (C-3) ; 70,8 (C-2) ; 70,4,70,3, 70,1,69,2 (4*C-CH20) ; 68,2 (C-5) ; 53,5 (C-OCH2CH20CO) ; 39,6 (C-OCH2CH20CO) ; 34,2 (C-l') ; 34 (C-4') ; 33 (C-16', C-17') ; 21,7 (C-18') ; 19,2 (C-3') ;17,5 (C-6) ; 13,8 (C-20') ; 12,8 (C-19').

(C-2); 70.4, 70.3, 70.1, 69.2 (4 * C-CH 2 O); 68.2 (C-5); 53.5 (C-OCH₂ÇH₂CCOC); 39.6 (C-OCH2CH2OCO); 34.2 (C-1 '); 34 (C-4 '); 33 (C-16 ', C-17'); (C-18 '); 19.2 (C-3 '); 17.5 (C-6); 13.8 (C-20 '); 12.8 (C-19 '). 13'-cis isomer: # (ppm): 166.2 (C-15 '); 151.8 (C-13 '); 139.9 (C-9 '); 137.6 (C-6 '); 137.3 (C-8 '); 134.9 (C-12 '); 131.2 (C-10 '); 130.2 (C-11 '); 129.7 (C-7 '); 128.7 (C-5 '); 118 (C-14 '); 99.9 (C-1); 72.7 (C-4); 71.5 (C-3); 70.8 (C-2); 70.4, 70.3, 70.1, 69.2 (4 * C-CH 2 O); 68.2 (C-5); 53.5 (C-OCH2CH2OCO); 39.6 (C-OCH2CH2OCO); 34.2 (C-1 '); 34 (C-4 '); 33 (C-16 ', C-17'); 21.7 (C-18 '); 19.2 (C-3 '), 17.5 (C-6); 13.8 (C-20 '); 12.8 (C-19 ').

a-L-rhamnopyranoside de 8-ss-ionylidène acétyl-3,6,8-trioxanonanyle 29
L'élution par un gradient de méthanol (0-4%) dans du dichlorométhane conduit à l'obtention de l'a-L-rhamnopyranoside de 8-p-ionylidène acétyl-3,6,8-trioxanonanyle 29 sous forme d'une huile jaune (Rdt=94%, isomères

tout-transl9'-cis 75/25). Rf 0,25 (CH2Cl2/MeOH 95/5). [a]D -28,6 (c=1,05, CHC13).

RMN 'H (CDCl3, 200MHz) isomère tout-trans : # (ppm) : 6,57 (1H, d, J8'-7'=16,5Hz, H-

8') ; 6,08 (1H, d, J7.-8-=16Hz, H-7') ; 5,77 (1H, s, H-10') ; 4,8 (1H, s, H-1) ; 4,29-4,22 (2H, m, H-OCH2CH90CO) ; 3,95-3,41 (10H, m, H-CH20) ; 2,31 (3H, d, J15'-Io,=0,9Hz, H-15') ; 2,02 (2H, m, H-4') ; 1,68 (3H, s, H-14') ; 1,64-1,55 (2H, m, H- 3') ; 1,48-1,43 (2H, m, H-2') ; (3H, d, J6-5=6,1Hz, H-6); 1,05 (3H, s, H-12') ; 1(3H, s, H-13').

isomère 9'-cis : (ppm) : 7,61 (1H, d, J7'-8'=16,5Hz, H-7') ; 6,57 (1H, d, J8'-7'=16,5Hz, H-8') ; 5,68 (1H, s, H-10') ; 4,8 (1H, s, H-1) ; 4,29-4,22 (2H, m, H-OCH2CH20CO) ; 3,95-3,41 (10H, m, H-CH20) ; 2,04 (3H, d,

J15'-Io,=0,9Hz, H-15') ; 2,02 (2H, m, H-4') ; 1,76 (3H, s, H-14') ; 1,64-1,55 (2H, m, H- MS (FAB + / NOBA) m / z: 601 [M + Na] +; 578 [M] +.

8-ss-ionylidene acetyl-3,6,8-trioxanonanyl aL-rhamnopyranoside 29
Elution with a gradient of methanol (0-4%) in dichloromethane leads to the production of 8-p-ionylidene acetyl-3,6,8-trioxanonanyl a-L-rhamnopyranoside 29 in the form of a yellow oil (Yield = 94%, isomers

all-transl9'-cis 75/25). Rf 0.25 (CH 2 Cl 2 / MeOH 95/5). [?] D -28.6 (c = 1.05, CHCl3).

1H NMR (CDCl 3, 200MHz) all-trans isomer: # (ppm): 6.57 (1H, d, J8'-7 '= 16.5Hz, H-1).

8 '); 6.08 (1H, d, J7-8- = 16Hz, H-7 '); 5.77 (1H, s, H-10 '); 4.8 (1H, s, H-1); 4.29-4.22 (2H, m, H-OCH2CH90CO); 3.95-3.41 (10H, m, H-CH 2 O); 2.31 (3H, d, J15'-Io, = 0.9 Hz, H-15 '); 2.02 (2H, m, H-4 '); 1.68 (3H, s, H-14 '); 1.64-1.55 (2H, m, H-3 '); 1.48-1.43 (2H, m, H-2 '); (3H, d, J6-5 = 6.1Hz, H-6); 1.05 (3H, s, H-12 '); 1 (3H, s, H-13 ').

9'-cis isomer: (ppm): 7.61 (1H, d, J7'-8 '= 16.5Hz, H-7'); 6.57 (1H, d, J8'-7 '= 16.5Hz, H-8'); 5.68 (1H, s, H-10 '); 4.8 (1H, s, H-1); 4.29-4.22 (2H, m, H-OCH2CH2CO3); 3.95-3.41 (10H, m, H-CH 2 O); 2.04 (3H, d,

J15'-Io, = 0.9 Hz, H-15 '); 2.02 (2H, m, H-4 '); 1.76 (3H, s, H-14 '); 1.64-1.55 (2H, m, H-

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 3 '); 1.48-1.43 (2H, m, H-2 '); 1.29 (3H, d, J6.5 = 6, 1Hz, H-6); 1.05 (3H, s, H-12 '); 1 (3H, s, H-13 ').

13C NMR (CDCl3,100MHz) all-trans isomer: # (ppm): 167.2 (C-11 '); 153.6 (C-9 '); 137.1 (C-6 '); 136.1 (C-8 '); 134 (C-7 '); 129.8 (C-5 '); 115.6 (C-10 '); 99.9 (C-1); 72.9 (C-4); 71.1 (C-3); 70.9 (C-2); 70.6, 70.5, 70.2, 69.4 (4 * C-CH 2 O); 68.5 (C-5); 66.4 (C-CH 2 O); 62.9 (C-CH 2 O); 39.8 (C-1 '); 34.6 (C-4 '); 29.4 (C-12 '); 29.3 (C-13 '); 22.1 (C-14 '); 19.5 (C-3 '); 18 (C-6); 14.1 (C-15 '). 9'-cis isomer: 5 (ppm): 166.7 (C-11 '); 152.7 (C-9 '); 137.6 (C-6 '); 136.5 (C-8 '); 132.7 (C-7 '); 129.8 (C-5 '); 118 (C-10 '); 99.9 (C-1); 72.9 (C-4); 71.1 (C-3); 70.9 (C-2); 70.6, 70.5, 70.2, 69.4 (4 * C-CH 2 O); 68.5 (C-5); 66.4 (CCH20); 40.2 (C-1 '); 34.5 (C-4 '); 29.4 (C-12 '); 29.3 (C-13 '); 22.2 (C-14 '); 19.5 (C-3 '); 17.5 (C-6); 14.1 (C-15 ').

a-L-rhamnopyranoside de 8-palmitoyl-3,6,8-trioxanonanyle 30
L'élution par un gradient de méthanol (0-3%) dans du dichlorométhane conduit à l'obtention de l'a-L-rhamnopyranoside de 8-palmitoyl- 3,6,8-trioxanonanyle 30 sous forme d'une huile incolore (Rdt=90%). MS (ESI + / ESI- / 30eV) m / z: 535 [M + Na] +. m / z: 511 [MH] -.

8-Palmitoyl-3,6,8-trioxanonanyl aL-rhamnopyranoside
Elution with a gradient of methanol (0-3%) in dichloromethane leads to 8-palmitoyl-3,6,8-trioxanonanyl α-L-rhamnopyranoside being obtained in the form of a colorless oil. (yield = 90%).

 Rf 0.5 (CH 2 Cl 2 / MeOH 95/5).

 [?] D29.7 (c = 1, CHCl3).

1,25-1,20 (27H, m, H-6, H-4'-H-15') ; 0,88 (3H, t, J]6'-15,=6,4Hz, H-13'). RMN 13C (CDCI3, 50MHz) 1H NMR (CDCl3, 200MHz) δ (ppm): 4.8 (1H, s, H1); 4.24-4.20 (2H, m, H-OCH2CH2OCO); 3.94 (1H, m, H-2); (13H, m, H-3, H-4, H-5, H-CH 2 O); 2.33 (2H, t, J2'-3 '= 7.6 Hz, H-2'); 2.14-1.98 (9H, s, H-COCH3); 1.56 (2H, m, H-3 ');

1.25-1.20 (27H, m, H-6, H-4'-H-15 '); 0.88 (3H, t, J) 6'-15, = 6.4Hz, H-13 '). 13C NMR (CDCl3, 50MHz)

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(C-5) ; 67,5, 66,7, 63,7 (3*C-CH20) ; 53,8 (C-OCH2ÇH20C0) ; 34,6 (C-2') ; 32,3 (C- 3') ; 30,1 (C-4', C-5') ; 30 (C-6', C-7', C-8', C-9') ; 29,9 (C-10') ; 29,8 (C-1 l') ; 29,7 (C-12') ; 29,6 (C-13') ; 25,3 (C-14') ; 23,1 (C-15') ; 21,3,21,2, 21,1 (3*C-COCH3) ; 17,8 (C-6) ; 14,5 (C-16'). # (ppm): 174.3 (C-1 '); 170.6, 170.5, 170.4 (3 ° C-COCH3); 98 (C-1); 71.5 (C-4); 71.2 (C-3); 71 (C-2); 70.5 (C-CH 2 O); 69.6 (C-CH 2 O); 69.4

(C-5); 67.5, 66.7, 63.7 (3 ° C-CH 2 O); 53.8 (C-OCH₂ÇH₂CCOC); 34.6 (C-2 '); 32.3 (C-3 '); 30.1 (C-4 ', C-5'); (C-6 ', C-7', C-8 ', C-9'); 29.9 (C-10 '); 29.8 (C-1 1 '); 29.7 (C-12 '); 29.6 (C-13 '); 25.3 (C-14 '); 23.1 (C-15 '); 21.3, 21.2, 21.1 (3 * C-COCH3); 17.8 (C-6); 14.5 (C-16 ').

 MS (ESI + / 30eV) m / z: 557 [M + Na] +.

Claims (11)

 ## STR5 ## wherein L is a spacer arm selected from ethylene glycol and / or propylene glycol polymers comprising from 1 to 5 carbon atoms. 10 polyalkylene glycol residues; amide and ester groups and polyhydroxyacids comprising from 1 to 10 carbon atoms, from 1 to 6 hydroxyl functions and from 1 to 6 carboxylic acid functions; n represents an integer ranging from 1 to 5; X represents a group chosen from the compounds designated Lip chosen from sterols, cannabinoids, retinoids, fatty acids, fat-soluble vitamins and polyisoprenic hydrocarbons.

 1. A compound characterized in that it corresponds to formula (I): [Su-A] n-X (I) in which: - Su represents a group chosen from

 molecules corresponding to formula (II): <Desc / Clms Page number 49>  wherein one or more of R1, R2, R3, Rt, R5 and R6 are a bond to a group Su-A-, and n is that number of bonds, one or more of R1, R2, R3, R4, R5 and R6 designated Y are chosen from linear, branched or cyclic, saturated or unsaturated, optionally aromatic, C6-C30 alkyls, optionally comprising one or more ether, ester, amide, thioether, carbamate or thiocarbamate functions in the alkyl chain; , several substituents R1, R2, R3, R4, R5 and R6 can be linked to form a single group, the other substituents R1, R2, R3, R4, R5 and R6 represent the hydrogen atom.  2. Compound according to claim 1, characterized in that it corresponds to formula (III): Su-A-Lip (III) 3. Compound according to any one of claims 1 and 2, characterized in that the Lip group is chosen from: cholesterol, animal and plant sterols, steroid hormones and bile acids, retinol, retinoic acid, carotenoids, tetrahydrocannabinols, iso-tetrahydrocannabinols, brucéol, flemengine, rubranine, palmitic acid, oleic acid, and all saturated or unsaturated C12-C36 fatty acids, linear or branched, with an even or odd number of carbons, functionalized or non-functionalized, vitamins D, E, K, terpene alcohols.  4. Compound according to any one of claims 1 to 3, characterized in that the bond between the spacer arm (A) and the residue (Lip) is by means of an ether bond, ether, ester, amide, thioether , thioester, carbamate, ureido.  5. Compound according to claim 1, characterized in that it corresponds to formula (II):

 wherein one or more of R1, R2, R3, R4, R5 and <Desc / Clms Page number 50> The other substituents R 1, R 2, R 3, R 4, R 5 and R 6 represent the hydrogen atom.  R6 are chosen from the groups corresponding to the formula Su-A-, one or more groups R1, R2, R3, R4, R5 and R6 designated Y are chosen from linear, branched or cyclic C6-C30 alkyls, saturated or unsaturated, optionally aromatic, optionally comprising one or more functions ether, ester, amide, thioether, carbamate, thiocarbamate in the alkyl chain, several substituents R1, R2, R3, R4, R5 and R6 can be bonded to form a single group;  6. Compound according to claim 5, characterized in that R1 = R3 = R5 = H.  7. Compound according to any one of claims 1 to 6, characterized in that it belongs to the list below:

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8. Lipid vesicles comprising at least one compound according to any one of claims 1 to 7.  9. Cosmetic and / or dermatological and / or pharmaceutical composition comprising at least one compound according to any one of Claims 1 to 7 in a support cosmetologically and / or dermatologically <Desc / Clms Page number 52>  and / or pharmaceutically acceptable.  10. Cosmetic and / or dermatological and / or pharmaceutical composition comprising the lipid vesicles according to claim 8 in a cosmetologically and / or dermatologically and / or pharmaceutically acceptable carrier.  11. Composition according to any one of claims 9 and 10, characterized in that it further comprises at least one active ingredient or a nutrient selected from: vitamins, hormones, plasmids, anticancer compounds, anti-cancer compounds, -Inflammatory, healing, anti-bacterial, anti-fungal compounds, vaccines, antioxidants, sunscreens.