The present invention relates to novel C-glycoside derivatives of given absolute configuration, to the process for synthesizing them, and to the compositions containing them.
The invention also relates to the cosmetic use of these C-glycoside compounds, as agents intended to stimulate the synthesis of glycosaminoglycans containing a D-glucosamine and/or N-acetyl-D-glucosamine residue, advantageously hyaluronic acid, and/or of proteoglycans, advantageously proteoglycans containing hyaluronic acid, by fibroblasts and/or keratinocytes.
The invention also relates to a cosmetic process for treating keratin materials using a composition containing at least one C-glycoside compound according to the invention.
Certain C-glycosides derivatives have demonstrated beneficial biological properties, in particular for combating ageing of the epidermis, and/or combating drying out of the skin. This is in particular the case with the compounds described in patent application WO-02/051828 filed in the applicant's name. These compounds act through stimulating the synthesis of glycosaminoglycans containing a D-glucosamine and/or N-acetyl-D-glucosamine residue, and are represented by formula (F) :
(Formula Removed)
in which S represents a monosaccharide or a polysaccharide, R represents various linear or cyclic radicals, and the group X can represent a group chosen from: -CO-, -CH(NR1R2)-, -CHR'- and -C(=CHR')-, it being possible for R' to represent various radicals, including the hydroxyl radical.
When R' is a hydroxyl radical, the corresponding compound of formula (F) corresponds to formula (F2):
(Formula Removed)
and has an asymmetric carbon, possibly existing in two epimeric forms R and S.
Taking into consideration also the fact that the sugar S can be linked to the side chain via an a or ß linkage, the compound that results therefrom, of formula (F3):
(Formula Removed)
can be in the form of 4 diastereoisomers denoted: (a, S) ; a, R) ; (p, S) ; and (p, R) .
The compounds of formula (F3) have up until now been described in the form of mixtures of several diastereoisomers. In particular, application W0-02/051828 discloses a process of synthesis that makes it possible to produce the derivatives in the form of a mixture of diastereoisomers:
(Formula Removed)
No method has made it possible to bring about the production of one of the forms in the diastereoiso-merically pure state.
The applicant has demonstrated that one of the diastereoisomers, (P, S) , can be obtained selectively, and studies have shown that it has a biological activity that is much greater than that of the compounds described in the form of a mixture in application WO-02/051828.
The present invention therefore relates to the C-glycoside compound of formula (I):
(Formula Removed)
in which,
5 represents a monosaccharide or a polysaccharide comprising up to 20 sugar units, preferably up to
6 sugar units, in pyranose and/or furanose form and of the D series, said mono- or polysaccharide having at least one hydroxyl function that is necessarily free and, optionally, one or more optionally protected amine functions,
the linkage represents a linkage in the ß-configuration,
R represents a linear or branched, saturated or unsaturated, alkyl, perfluoroalkyl or hydrofluoroalkyl chain comprising from 1 to 18 carbon atoms, a saturated or unsaturated cycloalkyl, cycloperfluoroalkyl or cyclohydro-fluoroalkyl ring comprising from 3 to 11 carbon atoms, or a phenyl or benzyl radical, it being possible for said chain or said ring to be optionally interrupted with one or more hetero atoms chosen from oxygen, sulphur, nitrogen and silicon, and optionally substituted with at least one radical chosen from -OR'1, -SR''1, -NR'''1R'2, -COOR"2, -CONHR'"2, -CN, halogen, perf luoroalkyl or hydrofluoroalkly comprising from 1 to 18 carbon atoms, a cycloalkyl radical comprising from 3 to 11 carbon atoms, an aryl radical or a heterocyclic radical, optionally substituted,
R'l, R'2, R"1, R"2, R'"1 and R'"2, which may be identical or different, represent a hydrogen atom, or a radical chosen from a linear or branched, saturated or unsaturated, alkyl, hydroxyl, perfluoroalkyl and/or hydrofluoroalkyl radical comprising from 1 to 30 carbon atoms, and also their physiologically acceptable salts.
Compounds of formula (I) are known from the publication "Preferred conformation of C-Glycosides. 1. Conformational similarity of glycosides and corresponding C-glycosides" Tse-Chong Wu, Peter G. Goekjian, Yoshito Kishi, J. Org. Chem., 1987, 52, p 4819-4823: C-ß-D-glycopyranoside-2-(S),3-dihydroxypropane (also called 2,6-anhydro-7-deoxy-L-gulononitol) (RN 54548-38-8) and C-ß-D-(2-deoxyglycopyranoside)-2-(S),3-dihydroxypropane (also called 4,8-anhydro-3,5-dideoxy-D-glycero-D-gulononitol) (RN 110352-39-1). The novel compounds (referred to as of formula (I)) corresponding to the compounds of formula (I) described above, with the exception of the two compounds mentioned above, are therefore part of the present invention.
An advantageous aspect of the invention concerns the compounds of formula (I) for which S represents a monosaccharide in which the hydroxyl function in the 3-position is free.
Advantageously, the preferred monosaccharides are chosen from D-glucose, D-galactose, D-mannose, D-xylose, D-lyxose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N-acetyl-D-glucosamine and N-acetyl-D-galactosamine. Preference will be given most particularly to D-glucose, D-xylose or N-acetyl-D-glucosamine, and very preferably to D-xylose.
Another particular aspect of the invention concerns the compounds of formula (I) for which S represents a polysaccharide as defined above.
Advantageously, the preferred polysaccharides contain up to 6 sugar units, and are chosen from D-maltose, D-lactose, D-cellobiose, D-maltotriose, a disaccharide combining a uronic acid chosen from D-iduronic acid and D-glucuronic acid with a hexosamine chosen from D-galactosamine, D-glucosamine, N-acetyl-D-galactosamine and N-acetyl-D-glucosamine, and an oligosaccharide containing at least one xylose advantageously chosen from xylobiose, methyl-ß-xylobioside, xylotriose, xylotetraose, xylopentaose and xylohexaose, and preferably xylobiose, which is made up of two molecules of xylose linked via a 1-4 linkage.
Another particular aspect of the invention concerns the compounds of formula (I) for which R represents a linear or branched, saturated or unsaturated, alkyl, perfluoroalkyl or hydrofluoroalkyl
chain comprising from 1 to 6 carbon atoms, a
cycloalkyl, cycloperfluoroalkyl or
cyclohydrofluoroalkyl ring comprising from 3 to 11 carbon atoms, or a phenyl or benzyl radical, it being possible for said chain or said ring to be optionally interrupted with one or more hetero atoms chosen from oxygen, sulphur, nitrogen and silicon, and optionally substituted with at least one radical chosen from -OR'1, -SR"1, -NR'"1R'2, -COOR"2, -CONHR'"2, -CN, halogen, perfluoroalkyl or hydrofluoroalkyl comprising from 1 to 6 carbon atoms, a cycloalkyl radical comprising from 3 to 11 carbon atoms, an aryl radical or a heterocyclic radical, optionally substituted.
Advantageously, R represents a linear or branched alkyl chain comprising from 1 to 6 carbon atoms or a cycloalkyl ring comprising from 3 to 11 carbon atoms. Preferably, R represents a linear or branched alkyl chain comprising from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, and better still from 1 to 3 carbon atoms, and even better still 1 or 2 carbon atoms.
Among the preferred alkyl groups, mention may be made of methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl groups, and preferably a methyl group.
The aryl groups that are preferred for implementing the invention are phenyl and naphthyl groups.
Among the heterocyclic groups that are preferred for implementing the present invention, mention may be made of furyl, thienyl, pyrazolyl, imidazolyl, pyridyl and pyrimidyl groups.
Among the C-glycoside compounds of formula (I), preference is given most particularly to the C-ß-D-xylopyranoside-2-(S)-hydroxypropane of formula:

(Formula Removed)
and the C-ß-D-fucopyranoside-2-(S)-hydroxypropane of formula:
(Formula Removed)
The present invention also relates to the process for preparing the compounds of formula (I) as defined above. This preparation process makes it possible to obtain the compounds of formula (I) selectively, in the form of a single diastereoisomer (p, S) .
The starting compound for the synthesis of the compound of formula (I) is the corresponding carbonylated compound of formula (II):
(Formula Removed)
in which S and R have the same meaning as above,- and
represents a linkage in the ß-configuration.
It is theoretically possible to carry out the reduction of the compound (II) by known methods. Conventional reducing agents can be used, for instance:
• aluminium hydrides and their salts (in particular their lithium, potassium or sodium salts), and also their derivatives such as, for example, Red-Al (sodium bis(2-methoxyethoxy)aluminiumhydride) or DIBAL-H (diisobutylaluminium hydride),
• borohydrides and their salts (in particular their lithium, potassium or sodium salts), and also their derivatives such as, for example, L-selectride or K-selectride (lithium triisobutylborohydride or potassium triisobutylborohydride, respectively),
• metals (for example sodium, potassium or lithium),
• catalytic hydrogenation in the presence of conventional catalysts such as platinum or palladium-on-charcoal.
The solvents conventionally used to carry out these reduction reactions are chosen from linear or branched primary, secondary or tertiary alcohols containing between 1 and 8 carbon atoms (for example
methanol, ethanol, isopropanol or tert-butanol), linear or cyclic ethers (for example ethyl ether, dioxane or tetrahydrofuran), aromatic compounds such as toluene, liquid ammonia, and water.
These processes for synthesis described in the prior art result however in a mixture of two diastereoisomeric forms in varying proportions, starting with a single compound of formula (II) of fixed absolute configuration. This is in particular the case with the process described in application WO-02/051828.
The applicant has discovered, surprisingly, that the choice of a specific reducing agent and of a particular solvent, used in the presence of an organic acid, makes it possible to produce a compound of formula (I) defined above, in the form of a single diastereoisomer ((5, S) , which can in particular be obtained without resorting to separation of the diastereoisomers.
The invention therefore relates to the
process for preparing a compound of formula (I), as
defined above, consisting in reacting a compound of
formula (II) :
(Formula Removed)
in which S and R have the same meaning as above,
in solution in a linear, branched or cyclic secondary
alcohol containing from 3 to 8 carbon atoms,
with a reducing agent comprising: (a) a metal borohydride of formula MBH4 in which M represents an alkaline metal, in the presence of an organic carboxylic or sulphonic acid containing from 1 to 10 carbon atoms, or (b) a reactive species or complex formed by the association of a metal borohydride with an organic acid and, optionally, a secondary alcohol.
In an advantageous aspect of the invention, the secondary alcohol used in the process above is isopropanol.
Another advantageous aspect of the invention concerns a preparation process as described above, in which the metal borohydride is chosen from sodium borohydride, lithium borohydride or potassium borohydride, and more particularly sodium borohydride.
The organic carboxylic acids that are suitable for implementing the present invention may in particular be chosen from aliphatic acids having from 1 to 10 carbon atoms, more particularly acetic acid, propanoic acid or butanoic acid, and aromatic acids having in particular from 6 to 10 carbon atoms, in particular benzoic acid.
The organic sulphonic acids that are suitable for implementing the present invention are chosen from aliphatic acids having from 1 to 10 carbon atoms, more particularly methanesulphonic acid or trifluoromethane-sulphonic acid, and aromatic acids having in particular
from 6 to 10 carbon atoms, in particular para-toluenesulphonic acid.
The preferred organic acid for implementing the process for preparing the compounds of formula (I) as defined above is acetic acid.
Alternatively and particularly effectively, the reaction consisting of reduction of the compound of formula (II) as defined above can be carried out, when it is available, by means of the reactive species or complex formed by the association of the metal borohydride with the organic acid and, optionally, secondary alcohol. Mention may in particular be made of sodium triacetoxyborohydride of formula NaBH(0Ac)3, which corresponds to the association of one molar equivalent of sodium borohydride with 3 molar equivalents of acetic acid.
In an advantageous aspect of the invention, the molar ratio of the organic acid to the metal borohydride used in the process above is at least 3.
In another particular aspect of the invention, the ratio of the secondary alcohol to the organic acid ranges between 1/4 and 20/1 by volume, and will advantageously be adjusted to a value equal to 9/2 by volume.
Preferred compounds of formula (II) for implementing the preparation process according to the
present invention are the C-p-D-xylopyranoside-2-propanone of formula:
(Formula Removed)
and the C-(3-D-fucopyranoside-2-propanone of formula:
(Formula Removed)
Another subject of the invention concerns a composition which comprises at least one C-glycoside derivative corresponding to formula (I) as defined above and a physiologically acceptable medium. In particular, the composition is suitable for topical application to the skin. The physiologically acceptable medium will preferably be a cosmetically acceptable medium, i.e. one which has no unpleasant odour, colour or appearance, and which does not generate any stinging, tightness or redness that is unacceptable to the user.
The composition according to the invention can comprise these C-glycoside derivatives alone or as a mixture in any proportion.
The term "physiologically acceptable medium" is understood to mean a medium that is compatible with the keratin materials of human beings, such as the

skin, the mucous membranes, the nails, the scalp and/or the hair.
The amount of C-glycoside derivative corresponding to formula (I) that can be used in the compositions according to the invention depends, of course, on the desired effect and should preferably be in an amount that is effective for stimulating the synthesis of hyaluronic acid and of proteoglycans (PCs) by fibroblasts and keratinocytes.
To give an order of magnitude, the composition according to the invention can contain at least one C-glycoside derivative corresponding to formula (I) in an amount representing from 0.00001% to 25% of the total weight of the composition, and preferably in an amount representing from 0.0001% to 10% of the total weight of the composition.
The composition according to the invention may be intended for cosmetic or pharmaceutical, particularly dermatological, application. Preferably, the composition according to the invention is intended for cosmetic application.
Advantageously, the compositions according to the invention are care compositions and/or antisun compositions and/or washing compositions and/or make-up compositions and/or make-up-removing compositions for the skin of the body and/or of the face and/or for the mucous membranes (for example the lips) and/or for the
scalp and/or for the hair and/or for the nails and/or for the eyelashes and/or for the eyebrows.
Another subject of the invention also relates to the use of the composition as defined above, for cosmetically treating and/or making up keratin materials, such as the hair, the skin, in particular the skin of the body and/or the face, the eyelashes, the eyebrows, the nails or the mucous membranes.
Another subject of the invention relates to the use of the composition as defined above, for -improving the appearance of keratin materials.
The composition according to the invention can be ingested, injected or applied to the skin (on any area of the skin of the body) , the hair, the nails or the mucous membranes (buccal, jugal, gingival, genital or conjunctival mucous membranes).
The composition according to the invention may be in any of the pharmaceutical forms normally used for topical application, in particular in the form of an aqueous, aqueous-alcoholic or oily solution, of an oil-in-water or a water-in-oil or multiple emulsion, of an aqueous or oily gel, of a liquid, pasty or solid anhydrous product, or of a dispersion of oil in an aqueous phase by means of spherules, it being possible for these spherules to be polymeric nanoparticles such as nanospheres and nanocapsules, or better still lipid vesicules of the ionic and/or non-ionic type. These
compositions are prepared according to the usual methods.
This composition may be more or less fluid and may have the appearance of a white or coloured cream, of an ointment, of a milk, of a lotion, of a serum, of a paste or of a mousse. It may optionally be applied to the skin in the form of an aerosol. It may also be in solid form, and for example in the form of a stick.
The composition that an be used according to the invention can also be a haircare composition, and in particular a shampoo, a hairsetting lotion, a medicated lotion, a styling cream or gel, a dye composition (in particular an oxidation dye composition) optionally in the form of a dyeing shampoo, a hair-restructuring lotion, a permanent-waving composition (in particular a composition for the first step of a permanent wave) , a lotion or a gel for preventing hair loss, an antiparasitic shampoo, etc.
When the composition that can be used according to the invention is an emulsion, the proportion of the fatty phase can range from 5% to 80% by weight, and preferably from 5% to 50% by weight relative to the total weight of the composition. The oils, the waxes, the emulsifiers and the coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the cosmetics
field. The emulsifier and the coemulsifier are present in the composition in a proportion ranging from 0.3% to 30% by weight, and preferably from 0.5% to 20% by weight relative to the total weight of the composition. The emulsion may also contain lipid vesicules.
In a known manner, the composition of the invention may also contain the adjuvants that are usual in the cosmetics and dermatological fields, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, pigments, chelating agents, odour absorbers and dyestuffs. The amounts of these various adjuvants are those conventionally used in the fields under consideration, and for example from 0.01% to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase, into the lipid vesicules and/or into the nanoparticles.
As oils or waxes that can be used in the invention, mention may be made of mineral oils (liquid petroleum jelly), plant oils (liquid fraction of karite butter, sunflower oil), animal oils (perhydrosqualene) , synthetic oils (purcellin oil), silicone oils or waxes (cyclomethicone) and fluoro oils (perfluoropolyethers) , beeswax, carnauba wax or paraffin wax. Fatty alcohols
and fatty acids (stearic acid) can be added to these oils.
As emulsifiers and coemulsifiers that can be used in the invention, mention may be made, for example, of fatty acids esters of polyethylene glycol, such as PEG-40 stearate and PEG-100 stearate, fatty acid esters of polyols, such as glyceryl stearate and sorbitan tristearate.
As hydrophilic gelling agents that can be used in the invention, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate/alkylacrylate copolymers, poly-acrylamides, polysaccharides such as hydroxypropyl-cellulose, natural gums and clays, and as lipophilic gelling agents, mention may be made of modified clays, for instance bentones, metal salts of fatty acids, for instance aluminium stearates, and hydrophobic silica.
As active agents, the composition according to the invention may comprise at least one compound chosen from: desquamating agents, humectants, emollients, agents for increasing keratinocyte differentiation, and mixtures thereof.
The C-glycoside derivatives corresponding to formula (I) exhibit notable activities of stimulating the synthesis of glycosaminoglycans (GAGs) containing a D-glucosamine and/or N-acetyl-D-glucosamine residue, advantageously hyaluronic acid, and/or of proteoglycans
(PGs), advantageously PGs containing hyaluronic acid, by fibroblasts and/or keratinocytes.
Thus, the present invention also relates to the cosmetic use of at least one compound of formula (I) as defined above, as an agent intended to stimulate the synthesis of glycosaminoglycans containing ■ a D-glucosamine and/or N-acetyl-D-glucosamine residue, and/or of proteoglycans, by fibroblasts and/or keratinocytes.
Another aspect of the invention relates to
the cosmetic use of at least one compound of formula
(I) as defined above, as an agent intended to stimulate
the synthesis of hyaluronic acid and/or of
proteoglycans containing hyaluronic acid.
More precisely, it has become apparent that the C-glycoside derivatives of formula (I), due to their stimulatory effect on the synthesis of GAGs containing a D-glucosamine and/or N-acetyl-D-glucosamine residue, advantageously hyaluronic acid, and/or of PGs, advantageously of PGs containing hyaluronic acid by fibroblasts and/or keratinocytes, make it possible:
to combat ageing of the epidermis. It is in fact known that ageing of the epidermis is, to a large extent, linked to a loss of hyaluronic acid,
to maintain and/or stimulate moisturization and/or to combat the drying out of the skin linked to an
insufficiency of the action of GAGs, in particular of hyaluronic acid. Such drying out is observed in particular on aged skin and is essentially linked to a loss of hyaluronic acid,
to improve the tonicity of the skin. It has in fact been observed that increasing the synthesis of PGs and of GAGs makes it possible to create a hydrated cellular environment that is favourable to exchanges of nutrients, of ions, of cytokine and of growth factors secreted by epidermal cells. Such an environment is also favourable to the elimination of toxic metabolites. This effect is thus reflected by healthy tonic skin,
to maintain or restore the suppleness and elasticity of the skin. This effect is associated with stimulating the synthesis of PGs and of GAGs, which makes it possible to create a hydrated environment for the matrix constituents, in particular at the dermo-epidermal junction, to promote micro-displacements between the components of this matrix during mechanical stress. Such an effect therefore contributes to making the skin more supple and more elastic,
to improve the mineralization of the epidermis, thus making the skin healthier and improving its vitality. This effect is associated with improving the synthesis of GAGs, which makes it possible to ensure good mineralization of the epidermis. In fact, GAGs can
bind ions, via their charge groups, and can contribute to the osmolarity of the epidermis. In this case also, good mineralization of the skin is synonymous with healthy skin showing good vitality,
to facilitate intercellular exchanges. This effect is also related to stimulating the synthesis of GAGs, which makes it possible to ensure correct differentiation of the epidermis since a destruction of hyaluronic acid gives rise to an opening of the intercellular spaces and epidermal acanthosis. This effect makes it possible to obtain skin that is more tonic, denser and more compact,
to improve the three-dimensional structure of the dermo-epidermal junction. This is also related to improving the synthesis of PGs and of GAGs, which makes it possible to ensure the spatial organization of the matrix constituents by reinforcing, for example at the dermo-epidermal junction, the binding between laminin-6 and nidogen (nidogen is a glycoprotein which, with laminin, attaches endothelial cells to type IV collagen),
to combat chapping and the cracked appearance of the skin,
to facilitate the migration of keratinocytes, allowing the formation of a horny layer of good quality,
to modulate the action of the growth factors and cytokines produced by the skin cells. Such an effect affords the cells the signals they need to carry out their function.
The present invention therefore also relates to a cosmetic process for combating ageing of the skin, comprising the application to the epidermis of a composition containing at least one compound of formula (I) as defined above.
The invention also relates to a cosmetic process for maintaining and/or stimulating the moisturization of the skin, comprising the application to the skin of a composition containing at least one compound of formula (I) as defined above.
The invention also relates to a cosmetic process for combating the drying out of the skin linked to the insufficiency of the action of GAGs containing a D-glucosamine and/or N-acetyl-glucosamine residue, in particular hyaluronic acid, comprising the application to the skin of a composition containing at least one compound of formula (I) as defined above.
The invention also relates to a cosmetic process for maintaining and/or restoring the suppleness and the elasticity of the skin, comprising the application to the epidermis of a composition containing at least one compound of formula (I) as defined above.
Finally, the invention relates to a cosmetic process for combating chapping and/or the cracked appearance of the skin, comprising the application to the skin of a composition containing at least one compound of formula (I) as defined above.
In the dermatological field, the compounds according to the invention facilitate cicatrization without scar . formation, thus making it possible to repair epidermal microtraumas which appear when the continuity of the skin is broken.
A subject of the invention is therefore also the use of at least one compound of formula (I) as defined above, for producing a dermatological composition intended to promote skin cicatrization.
The examples which follow illustrate the invention without limiting the scope thereof. The compounds are, depending on the case, given as chemical names or as CTFA (International Cosmetic Ingredient Dictionary and Handbook) names. The proportions are given as percentages by weight, unless otherwise indicated.
Example 1: Production of C-ß-D-xylopyranoside-2-(S)-hydroxypropane
2 ml of acetic acid, followed rapidly by 120 mg (1.2 eq.) of sodium borohydride as granules are
added to a solution of 500 mg of C-p-D-xylopyranoside-2-propanone (described in Example 1 of application WO-02/051828) in 9 ml of isopropanol. The medium is left at ambient temperature for 30 minutes with stirring. 120 mg (1.2 eq.) of sodium borohydride as granules are then added. The reaction medium is left for 1 hour at ambient temperature with stirring. 10 ml of acetone are then added and, after stirring for 30 minutes at ambient temperature, the reaction medium is concentrated under vacuum. The residue obtained is purified by silica gel chromatography so as to selectively produce the expected compound C-ß-D-xylopyranoside-2-(S) -hydroxypropane with a 95% yield.
Physico chemical characteristics of the compound:
Melting point: 120-122°C
Optical rotation: - 37° (at 20°C in methanol, and at a
concentration [C] = 1 g/100 ml)
1H NMR: 1.03 (t, 3H) ; 1.46 (m, 1H) ; 1.71 (m, 1H) ; 2.85
(m, 1H); 2.94 (m, 1H); 2.99 (m, 2H); 3.24 (m, 1H); 3.67
(m, 1H) ; 3.77 (m, 1H) .
Structure confirmed by X-ray diffraction.
Example 2: Production of C-ß-D-xylopyranoside-2- (S)-hydroxypropane
The expected compound is obtained according the process described in Example 1, replacing the 2 ml of acetic acid and the sodium borohydride with two times 1.2 equivalents of sodium triacetoxyborohydride
(NaBH(OAc)3) •
The product is obtained with a quantitative yield, and selectively in ((3, S) form. The physico chemical characteristics are identical .in all respects to those obtained in Example 1.
Example 3: Study of the effect of C-glycoside derivatives according to the invention on the synthesis of hyaluronic acid
The study is carried out by measuring the incorporation of radioactive glucosamine into the matrix neosynthesized by normal human dermal fibroblast cultures. The incorporation of radioactive glucosamine indicates specific neosynthesis of glycosaminoglycans via incorporation of the sulphated form of this glucosamine.
Normal human dermal fibroblasts are seeded in the conventional culture medium and are then preincubated for 24 hours. The culture medium is then replaced with the test compounds at concentrations of 0.3, 1 and 3 mM; or culture medium (control); or TGFß at 10 ng/ml (quality control). The cells are incubated
for 72 hours with the addition of 35S-sulphate during the final 24 hours of culture. The GAGs in the matrix are extracted with a chaotropic buffer and then purified by ion exchange chromatography (adsorption of the anionic molecules onto Q-sepharose beads under high stringency conditions, followed by desorption of the weakly and moderately anionic molecures with urea). The radioactivity incorporated into the very cationic molecules that have remained on the support is counted by liquid scintillation.
The results are expressed as percentage relative to the control:

(Table Removed)
(*) : The comparative example is the compound described
in Example 4 of application WO-02/051828, in the form of a racemic mixture (ß, S) (P, R).
The values measured are given in counts per minute
(cpm) sd: standard deviation p: confidence interval n: replicates
These results indicate that the compounds of formula (I) of the present invention having a (|3, S) conformation stimulate the neosynthesis of GAGs to a much greater extent than the stimulation obtained with the compounds of the prior that are in the form of a mixture, thus showing the superiority of one of the two diastereoisomers over the other.
Example 5: Preparation of C-ß-D-fucopyranoside-2-(S)-hydroxypropane
a) Preparation of C-ß-D-fucopyranoside-2-propanone:
(Formula Removed)
2 g of D-fucose are dissolved in 20 ml of water, in a 50 ml three-necked flask equipped with a condenser, a thermometer and magnetic stirring, and then penta-2,4-dione (1.51 g, 1.2 eq) and sodium bicarbonate (1.53 g, 1.5 eq) are added. The mixture is stirred for 18 hours at 90°C. The reaction medium is then washed with
dichloromethane and concentrated under vacuum. The brown oil obtained is purified by silica gel chromatography so as to produce the expected compound C-ß-D-fucopyranoside-2-propanone with a 92% yield (2.3 g).
Mass spectometry is in conformity, b) Production of C-p-D-fucopyranoside-2-(S)-hydroxypropane:
(Formula Removed)
7.5 ml of acetic acid, followed rapidly by 510 mg (1.2 eq.) of sodium borohydride as granules, are added to a solution of 2.3 g of C-p-D-fucopyranoside-2-propanone in 33 ml of isopropanol. The medium is left at ambient temperature for 30 minutes with stirring. 510 mg (1.2 eq.) of sodium borohydride as granules are then added. The reaction medium is left for 8 hours at ambient temperature with stirring. 10 ml of acetone are then added and, after stirring at ambient temperature for 12 hours, the reaction medium is concentrated under vacuum. The residue obtained is purified by silica gel chromatography so as to selectively produce the expected compound C-ß-D-fucopyranoside-2-(S)-hydroxypropane with a 65% yield.
NMR (500 MHz) and mass spectrometry are in conformity with the expected product.
Example 4: Compositions according to the invention
Composition 1: Oil-in-water (0/W) cream
Glyceryl monostearate 6.0%
Stearyl alcohol 4.0%
Liquid petroleum jelly 10.0%
Silicone oil 5.0%
C-p-D-Xylopyranoside-2-(S)-hydroxypropane 10.0%
Glycerol 8.0%
Carboxyvinyl polymer of the Carbopol type 0.3%
Preserving agents 0.4%
Fragrance 0.5%
Triethanolamine 0.3%
Water qs 100%
Composition 2: Water-in-oil (W/O) cream
Octyl dodecanol 10.0%
Magnesium stearate 4.0%
Natural beeswax 5.0%
Sorbitan sesquioleate 4.5%
Glyceryl mono- and distearate and potassium
stearate 1.0%
Liquid petroleum jelly 22.0%
Jojoba oil 4.0%
C-p-D-Xylopyranoside-2-(S)-hydroxypropane 2.5%
Preserving agent 0.4%
Fragrance 0.6%
Water qs 100%
Composition 3: Oil-in-water (O/W) cream
Glyceryl monostearate 6.0%
Stearyl alcohol 4.0%
Liquid petroleum jelly 10.0%
Silicone oil 5.0%
C-ß-D-Fucopyranoside-2-(S)-hydroxypropane 10.0%
Glycerol 8.0%
Carboxyvinyl polymer of the Carbopol type 0.3%
Preserving agents 0.4%
Fragrance 0.5%
Triethanolamine 0.3%
Water qs 100%

CLAIMS
1. C-glycoside compound corresponding to formula (I') below:
(Formula Removed)
in which:
S represents a monosaccharide or a polysaccharide of up to 20 sugar units, in pyranose and/or furanose form and of the D series, said mono- or polysaccharide having at least one hydroxyl function that is necessarily free and, optionally, one or more optionally protected amine functions,
the linkage represents a linkage in the (3-configuration,
R represents a linear or branched, saturated or unsaturated, alkyl, perfluoroalkyl or hydrofluoro-alkyl chain comprising from 1 to 18 carbon atoms, a cycloalkyl, cycloperfluoroalkyl or cyclohydro-fluoroalkyl ring comprising from 3 to 11 carbon atoms, or a phenyl or benzyl radical, it being possible for said chain or said ring to be optionally interrupted with one or more hetero atoms chosen from oxygen, sulphur, nitrogen and silicon, and optionally substituted with at least one radical chosen from -OR'1, -SR''1, -NR'"1R'2,
-COOR"2, -CONHR'"2, -CN, halogen, perf luoroalkyl or hydrofluoroalkyl comprising from 1 to 18 carbon atoms, and/or at least one cycloalkyl radical comprising from 3 to 11 carbon atoms, an aryl radical or a heterocyclic radical, optionally substituted,
R'1, R'2, R"1, R"2, R"'1, R"'2, which may be identical or different, represent a hydrogen atom, or a radical chosen from a linear or branched, saturated or unsaturated, alkyl, hydroxyl, perfluoroalkyl and/or hydrofluoroalkyl radical comprising from 1 to 30 carbon atoms, and also their physiologically acceptable salts, with the exception of the compounds C-ß-D-glycopyranoside-2-(S) , 3-dihydroxypropane and C-ß-D-(2-deoxyglycopyranoside)-2-(S),3-dihydroxypropane.
2. Compound of formula (I') according to Claim 1, characterized in that the group R represents a linear or branched alkyl chain comprising from 1 to 18 carbon atoms, preferably from 1 to 6 carbon atoms.
3. Compound of formula (I') according to either of Claims 1 and 2, characterized in that S represents a monosaccharide having at least one hydroxyl function that is necessarily free and, optionally, one or more optionally protected amine functions.
4. Compound of formula (I') according to one of Claims 1 to 3, characterized in that S represents a monosaccharide in which the hydroxyl function in the 3-position is free.
5. Compound of formula (I') according to one of Claims 1 to 4, characterized in that S represents a monosaccharide chosen from D-glucose, D-galactose, D-mannose, D-xylose, D-lyxose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N-acetyl-D-glucosamine and N-acetyl-D-galactosamine.
6. Compound of formula (I') according to one of Claims 1 to 5, characterized in that S represents a D-xylose residue.
7. Compound of formula (I') according to one of Claims 1 to 6, which is C-ß-D-xylopyranoside-2-(S)-hydroxypropane or C-ß-D-fucopyranoside-2- (S) -hydroxypropane.
8. Process for preparing a compound of formula (I') according to Claim 1, consisting in reacting a compound of formula (II):
(Formula Removed)
in which S and R have the same meaning as in Claim 1, in solution in a linear, branched or cyclic secondary alcohol containing from 3 to 8 carbon atoms, with a reducing agent comprising: (a) a metal borohydride of formula MBH4 in which M represents an alkaline metal, in the presence of an organic
carboxylic or sulphonic acid containing from 1 to 10 carbon atoms, or (b) a reactive species or complex formed by the association of a metal borohydride with an organic acid and, optionally, a secondary alcohol.
9. Process according to Claim 8, characterized in that the secondary alcohol is isopropanol.
10. Process according to either of Claims 8 and 9, characterized in that the organic acid is chosen from acetic acid, propanoic acid, butanoic acid, benzoic acid, methanesulphonic acid, trifluoromethanesulphonic acid and para-toluenesulphonic acid.
11. Process according to Claim 10, characterized in that the organic acid is acetic acid.
12. Process according to one of Claims 8 to 11, characterized in that the metal borohydride is chosen from sodium borohydride, potassium borohydride and lithium borohydride.
13. Process according to Claim 12, characterized in that the metal borohydride is sodium borohydride.
14. Process according to one of Claims 8 to
13, characterized in that the molar ratio of the
organic acid to the metal borohydride is at least 3.
15. Process according to one of Claims 8 to
14, characterized in that the ratio of the secondary
alcohol to the organic acid ranges between 1/4 and 20/1 by volume.
16. Process according to Claim 15, characterized in that the ratio of the secondary-alcohol to the organic acid is equal to 9/2 by volume.
17. Process according to Claim 8, characterized in that the reducing agent is made up of the reactive. species or complex formed by the association of a metal borohydride and an organic acid and, optionally, a secondary alcohol.
18. Process according to Claim 17, characterized in that the reducing agent is sodium triacetoxyborohydride.
19. Process according to one of Claims 8 to 18, characterized in that the compound of formula (II) is C-p-D-xylopyranoside-2-propanone.
20. Composition comprising, in a physiologically acceptable medium, at least one compound of formula (I):
(
in which,
S represents a monosaccharide or a polysaccharide of up to 20 sugar units, in pyranose and/or furanose form and of the D series, said mono- or polysaccharide having at least one hydroxyl function that is necessarily free and, optionally, one or more optionally protected amine functions,
the linkage represents a linkage in the ß-configuration,
R represents a linear or branched, saturated or unsaturated, alkyl, perfluoroalkyl or hydrofluoroalkyl chain comprising from 1 to 18 carbon atoms, a cycloalkyl,"cycloperfluoroalkyl or cyclohydrofluoroalkyl ring comprising from 3 to 11 carbon atoms, or a phenyl or benzyl radical, it being possible for said chain or said ring to be optionally interrupted with one or more hetero atoms chosen from oxygen, sulphur, nitrogen and silicon, and optionally substituted with at least one radical chosen from -OR'1, -SR''1, -NR'''1R'2, -COOR"2, -CONHR'"2, -CN, halogen, perf luoroalkyl or hydrofluoroalkyl comprising from 1 to 18 carbon atoms, and/or at least one cycloalkyl radical comprising from 3 to 11 carbon atoms, an aryl radical or a heterocyclic radical, optionally substituted,
R'1, R'2, R"1, R"2, R"'1, R'"2, which may be identical or different, represent a hydrogen atom, or a radical chosen from a linear or branched, saturated or unsaturated, alkyl, hydroxyl, perfluoroalkyl and/or hydrofluoroalkyl radical comprising from 1 to 30 carbon atoms, and also their physiologically acceptable salts.
21. Composition according to the preceding claim, characterized in that, for the compound of formula (I), the group R represents a linear or branched alkyl chain comprising from 1 to 18 carbon atoms, preferably from 1 to 6 carbon atoms.
22. Composition according to Claim 20 or 21, characterized in that, for the compound of formula (I), S represents a monosaccharide having at least one hydroxyl function that is necessarily free and, optionally, one or more optionally protected amine functions.
23. Composition according to any one of Claims 20 to 22, characterized in that, for the compound of formula (I), S represents a monosaccharide in which the hydroxyl function in the 3-position is free.
24. Composition according to any one of Claims 20 to 23, characterized in that, for the compound of formula (I), S represents a monosaccharide chosen from D-glucose, D-galactose, D-mannose, D-xylose, D-lyxose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N-acetyl-D-glucosamine and N-acetyl-D-galactosamine.
25. Composition according to any one of Claims 20 to 24, characterized in that, for the compound of formula (I), S represents a D-xylose residue.
26. Composition according to any one of Claims 20 to 25, characterized in that the compound of formula (I) is C-ß-D-xylopyranoside-2-(S)-hydroxypropane or C-ß-D-fucopyranoside-2-(S)-hydroxypropane.
27. Composition according to any one of Claims 20 to 26, characterized in that it is suitable for topical application to the skin.
28. Composition according to any one of Claims 20 to 27, characterized in that the physiologically acceptable medium is a cosmetically acceptable medium.
29. Composition according to any one of Claims 20 to 28, characterized in that the compound of formula (I) is present in an amount ranging from 0.00001% to 25% by weight relative to the total weight of the composition.
30. Composition according to the preceding claim, characterized in that the compound of formula (I) is present in an amount ranging from 0.0001% to 10% by weight relative to the total weight of the composition.
31. Cosmetic process for combating ageing of the skin, comprising the application to the epidermis of a composition containing at least one compound of formula (I) as defined in one of Claims 20 to 26.
32. Cosmetic process for maintaining and/or stimulating the moisturization of the skin, comprising the application to the skin of a composition containing at least one compound of formula (I) as defined in one of Claims 20 to 26.
33. Cosmetic process for combating the drying out of the skin linked to the insufficiency of the action of GAGs containing a D-glucosamine and/or N-acetyl-glucosamine residue, in particular hyaluronic acid, comprising the application to the skin of a composition containing at least one compound of formula (I) as defined in one of Claims 20 to 26.
34. Cosmetic process for maintaining and/or restoring the suppleness and elasticity of the skin, comprising the application to the epidermis of a composition containing at least one compound of formula (I) as defined in one of Claims 20 to 26.
35. Cosmetic process for combating chapping and/or the cracked appearance of the skin, comprising the application to the skin of a composition containing at least one compound of formula (I) as defined in one of Claims 20 to 26.
36. Use of at least one compound of formula (I) as defined in one of Claims 20 to 26, for producing a dermatological composition intended to promote skin cicatrization.
37. Cosmetic use of at least one compound of formula (I) as defined on one of Claims 20 to 26, as an agent intended to stimulate the synthesis of glycosaminoglycans containing a D-glucosamine and/or N-acetyl-D-glucosamine residue, and/or of proteoglycans, by fibroblasts and/or keratinocytes.
38. Cosmetic use of the at least one compound of formula (I) as defined in one of Claims 20 to 26, as an agent intended to stimulate the synthesis of hyaluronic acid and/or of proteoglycans containing hyaluronic acid.