FR3083109A1 - PROCESS FOR THE TREATMENT OF KERATINIC MATERIALS WITH C-GLYCOSIDES5-OXAZOLIDINE-2,4-DIONES COMPOUNDS, COMPOUNDS AND COSMETIC COMPOSITION CONTAINING THEM - Google Patents

Abstract

The present invention relates to a cosmetic treatment process for keratin materials, comprising the application to them, such as the skin, of a composition comprising a compound (I) The invention relates in particular to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below as a whitening, lightening and / or depigmenting agent for keratin materials, in particular for the skin.

Description

PROCESS FOR THE TREATMENT OF KERATINIC MATERIALS WITH C-GLYCOSIDES5-OXAZOLIDINE-2,4-DIONES COMPOUNDS, COMPOUNDS AND COSMETIC COMPOSITION CONTAINING THEM

The present invention relates to the cosmetic use of C-glycoside compounds, in particular their use for depigmenting and / or bleaching keratin materials and in particular the skin, of new C-glycoside compounds, the compositions in particular the cosmetic compositions which contain them and a process for treating keratinous materials using said C-glycosides. At different times in their life, some people see darker and / or more colored spots appear on the skin and more particularly on the hands and face, giving the skin heterogeneity. These spots are due in particular to a high concentration of melanin in the keratinocytes located on the surface of the skin.

The use of harmless topical depigmenting substances with good efficacy is particularly sought in order to treat pigment spots. The mechanism for the formation of skin pigmentation, i.e. the formation of melanin, is particularly complex and schematically involves the following main stages:

Tyrosine -> Dopa -> Dopaquinone -> Dopachrome -> Melanin

Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1) is the essential enzyme involved in this series of reactions. It catalyzes in particular the reaction of transformation of tyrosine into Dopa (dihydroxyphenylalanine) thanks to its hydroxylase activity and the reaction of transformation of Dopa into dopaquinone thanks to its oxidase activity. This tyrosinase only works when it is maturing under the action of certain biological factors.

A substance is recognized as depigmenting if it acts directly on the vitality of the epidermal melanocytes where melanogenesis takes place, and / or if it interferes with one of the stages of melanin biosynthesis either by inhibiting one of the enzymes involved in melanogenesis, or by intercalating as a structural analogue of one of the chemical compounds in the melanin synthesis chain, a chain which can then be blocked and thus ensure depigmentation.

Arbutin and kojic acid are known as depigmenting agents for the skin. We have looked for substances which have an effective depigmenting action.

There nevertheless remains the need for a new whitening agent for keratin materials and in particular for human skin which is stable in a composition, easily formulated in particular in aqueous formulations, or alternatively which has a reinforced action so that it can be used in lower amount, which greatly decreases the side effects that can be observed.

In this regard, the Applicant has surprisingly and unexpectedly discovered that C-glycoside 5-oxazolidine-2,4-diones compounds exhibit good depigmenting activity, even at low concentration, without showing cytotoxicity.

A first object of the invention is a method of cosmetic treatment of keratin materials, in particular of the skin, using at least one compound of formula (I) as defined below or a cosmetic composition comprising at least one compound of formula (I).

The invention relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below, in particular of at least one compound of formula (I '). (I ”), (I” ”), (a), (l” ^a ) and / or (l ”” a) and even more particularly of at least one compound 1a, 1b, 1c, 1d and / or 1 to 8 defined below as a whitening, lightening and / or depigmenting agent for keratin materials, especially the skin.

The subject of the invention is also a method of non-therapeutic cosmetic treatment of depigmentation, lightening and / or bleaching of keratin materials, in particular of the skin, comprising the application to the skin of at least one compound of formula ( I), in particular of at least one compound of formula (I '), (I ”), (I” ”), (a), (l” a) and / or (l ”” a) and again more particularly at least one compound 1a, 1b, 1c, 1d and / or 1 to 8 as defined below or of a composition comprising them.

A subject of the invention is also the dermatological use of at least one compound of formula (I) as defined below, in particular of at least one compound of formula (I '). (I ”), (I” ”), (a), (l” ^a ) and / or (l ”” a) and even more particularly of at least one compound 1a, 1b, 1c, 1d and / or 1 to 8 to depigment the skin, lighten and / or whiten it.

The compounds of formula (I) in accordance with the invention, as defined below, in particular the compounds of (I '), (I ”), (I” ”), (a), (l” a ) and / or (l ”” a) and even more particularly of at least one compound 1a, 1b, 1c, 1d and / or 1 to 8 make it possible to depigment and / or to lighten effectively, even to whiten, the materials keratin, especially the skin of humans. They are in particular intended to be applied to the skin of individuals having brownish pigmentation spots, spots of senescence, or to the skin of individuals wishing to combat the appearance of a brownish color originating from melanogenesis.

By keratin materials within the meaning of the present invention, is meant keratin materials of human beings, and in particular the skin, hair, eyelashes, hair, lips and nails of human beings.

The compounds of formula (I) in accordance with the invention can also make it possible to depigment and / or lighten the hairs, the eyelashes, the hair, as well as the lips and / or the nails.

More particularly, keratin materials designate the skin of human beings.

A subject of the invention is also the new compounds of formula (I), (I '), (I ”), (I” ”), (a), (l” a) and / or (l ”” a) and even more particularly the compounds 1a, 1b, 1c, 1d and / or 1 to 8 as defined below.

The subject of the invention is likewise a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound of formula (I) as defined below, in particular at least one compound of formula (I '), (I ”), (I” ”), (a), (l” a) and / or (l ”” a) and even more particularly of at least one compound 1a, 1b, 1c, 1d and / or 1 to 8 described below.

Other characteristics, objects and advantages of the invention will appear more clearly on reading the description and the examples which follow.

In what follows, and unless otherwise indicated, the limits of a domain of values are included in this domain.

The expression "at least one" is equivalent to the expression "one or more".

For the purposes of the present invention, the term “physiologically acceptable medium” is intended to denote a medium without odor or unpleasant appearance, and which is perfectly compatible with the topical route of administration. In the present case where the composition is intended to be administered topically, that is to say by application to the surface of the keratin material in question, such a medium is in particular considered to be physiologically acceptable when it does not generate discomfort, such as tingling or tightness unacceptable to the user.

By “keratin material” is meant in the present invention a preferably human keratin material, and in particular the skin (preferably human skin), and even more particularly the skin of the body and / or of the face.

The skin area can be chosen in particular from;

- hands,

- the face, in particular the forehead, the cheeks or the outline of one eye (periocular), and in particular the crow's feet, the area below the eye (pocket), or the eyelids, armpits.

Within the meaning of the present invention, and unless a different indication is given: the saturated or unsaturated cycles, possibly condensed, can also be optionally substituted;

the “alkyl” radicals are hydrocarbon, saturated, linear or branched radicals, generally C1-C18, particularly C1-C10, preferably C1-C6 alkyl radicals; as C1-C14 alkyl group, mention may in particular be made of methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl, isobutyl, sec-butyl, pentyl, isopentyl, neopentyl, n-hexyl, n- groups. heptyl and octyl;

the “alkenyl” or “alkenyl” radicals are hydrocarbon radicals, linear or branched, C 2 -C 18 unsaturated; preferably comprising one or more double bonds, conjugated or not, such as ethylene, propylene, butylene, pentylene, methyl-2-propylene, prenyl and decylene;

the “alkynyl” or “alkynyl” radicals are hydrocarbon radicals, linear or branched, C 2 -C 18 unsaturated; preferably comprising one or more triple bonds;

the “aryl” radicals are mono or polycyclic carbon radicals, condensed or not, preferably comprising from 6 to 30 carbon atoms and of which at least one ring is aromatic; preferably the aryl radical is chosen from a phenyl, biphenyl, naphthyl, indenyl, anthracenyl and tetrahydronaphthyl radical, more preferably aryl denotes phenyl;

the “alkoxy” or “alkoxy” radicals are alkyl-oxy radicals with alkyl as defined above, the alkyl part of the alkoxy is generally C1-C18, preferably C1-C10, such as methoxy, ethoxy, propoxy and butoxy, when unsaturated is mentioned, this implies that the alkoxy group may represent an alkenyl-oxy or alkynyl-oxy group with alkenyl and alkynyl as defined above;

the “cycloalkyl” radicals are C4-C8 cycloalkyl radicals, preferably the cyclopentyl and cyclohexyl radicals; the cycloalkyl radicals can be cycloalkyl radicals substituted, in particular by alkyl, alkoxy, carboxylic acid, hydroxy, amine and ketone groups;

the “heterocycloalkyl” radicals are heterocyclic radicals comprising from 4 to 8 members, saturated or partially unsaturated, non-aromatic, which comprises from 1 to 3 heteroatom in particular chosen from oxygen, sulfur and nitrogen, preferably morpholino radicals, piperazino and piperidino; the heterocycloalkyl radicals can be radicals substituted, in particular by alkyl, alkoxy, carboxylic acid, hydroxy, amine and ketone groups;

the “aryl” or “heteroaryl” radicals can be substituted by at least one atom or group carried by at least one carbon atom, chosen from:

i) (Ci-Cio) alkyl, preferably Ci-Cs, optionally substituted by one or more radicals chosen from hydroxy radicals, (Ci-C4) optionally unsaturated alkoxy, (poly) hydroxy-C2-C4 alkoxy, acylamino, amino substituted by two identical or different C1-C4 alkyl radicals, optionally carrying at least one hydroxy group or, the two radicals being able to form, with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7-membered, preferably 5 or 6-membered, saturated or unsaturated, optionally substituted, optionally comprising another heteroatom identical or different from nitrogen; ii) halogen; iii) hydroxy; iv) C1-C4 alkoxy;

v) C1-C10 alkoxycarbonyl; vi) C2-C4 (poly) hydroxyalkoxy; vii) C2-C4 alkylcarbonyloxy, preferably -O-acetyl or acetyloxy; viii) 5- or 6-membered heterocycloalkyl; ix) 5 or 6-membered heteroaryl, and optionally substituted by a (C1-C4) alkyl radical, preferably methyl; x) amino substituted by one or two identical or different C 1 -C 6 alkyl radicals optionally carrying at least: a) a hydroxy group, b) amino optionally substituted by one or two optionally substituted C 1 -C 3 alkyl radicals, said alkyl radicals being able to form, with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7 members, saturated or unsaturated optionally substituted optionally comprising at least one other heteroatom different or not from nitrogen, c) a group quaternary ammonium -N ⁺ R'R ”R '”, Q' for which R ', R ”, R'”, identical or different represent a hydrogen atom, or a C1-C4 alkyl group; and Q 'represents the anionic counterion such as the halide, d) a heteroaryl radical with 5 or 6 members, and optionally substituted by a (C1-C4) alkyl radical, preferably methyl; xi) acylamino (-N (R) -C (O) -R ') in which the radical R is a hydrogen atom, a C1-C4 alkyl radical optionally carrying at least one hydroxy group and the radical R 'is a C1-C2 alkyl radical; xii) carbamoyl ((R) 2N-C (O) -) in which the radicals R, which may or may not be identical, represent a hydrogen atom, a C1-C4 alkyl radical optionally carrying at least one hydroxy group; xiii) alkylsulfonylamino (R'S (O) 2-N (R) -) in which the radical R represents a hydrogen atom, a C1-C4 alkyl radical optionally carrying at least one hydroxy group and the radical R 'represents a C1-C4 alkyl radical, a phenyl radical; xiv) aminosulfonyl ((R) 2N-S (O) 2-) in which the radicals R, which may or may not be identical, represent a hydrogen atom, a C1-C4 alkyl radical optionally carrying at least one hydroxy group, xv) carboxy in acid or salified form (preferably with an alkali metal or ammonium, substituted or not); xvi) cyano; xvii) benzyloxycarbonyl; xviii) polyhaloalkyl, preferably trifluoromethyl; xix) a phenylcarbonyloxy group optionally substituted by one or more hydroxy groups; and xx) a phenyl group optionally substituted by one or more hydroxy groups;

the “heteroaryl” radicals are radicals comprising in at least one ring one or more heteroatoms particularly chosen from O, N and S, preferably O or N, optionally substituted by in particular one or more alkyl, alkoxy, carboxy, hydroxy, amine groups or ketone, and at least one cycle of which is aromatic. These rings may contain one or more oxo groups on the carbon atoms of the heteroaryl; among the heterocyclic radicals which can be used, mention may in particular be made of furyl, pyrannyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, thienyl, pyrimidinyl groups; even more preferably, the heterocyclic groups are condensed groups such as benzofurannyl, chromenyl, xanthenyl, indolyl, isoindolyl, quinolyl, isoquinolyl, chromannyl, isochromannyl, indolinyl, isoindolinyl, coumarinyl, isocoumarinyl, these groups being able to be substituted, in particular one or more OH groups;

the “protective group” or “PG” of the “hydroxy” or “amino” function is known to a person skilled in the art, the two works “Protective Groups in Organic Synthesis”, TW Greene, John Willey & Sons ed ., NY, 1981, pp. 193-217; "Protecting Groups", P. Kocienski, Thieme, 3 ^rd ed., 2005.

In particular, the protective group is chosen from:

(C1-C6) alkyl (thio) carbonyl such as formyl, acetyl or t-butylcarbonyl;

(di) (tri) halo (Ci-C6) alkyl (thio) carbonyl such as trifluoroacethyl (TFA);

(Ci-C6) alkoxy (thio) carbonyl such as methoxycarbonyl, ethoxycarbonyl, isobutyloxycarbonyl, t-butyloxycarbonyl (BOC), vinyloxycarbonyl, allyloxycarbonyl;

(di) (tri) halo (Ci-C6) alkoxy (thio) carbonyl such as 2,2,2-trichloroethylcarbonyl;

(Ci-Cejalkylthio-thiocarbonyle;

(Di) (tri) halo (Ci-C6) alkylthio-thiocarbonyl;

(di) (C1-C6) (alkyl) aminocarbonyl;

(Di) (Ci-C6) (alkyl) aminothiocarbonyl;

arylcarbonyl optionally substituted as phenylcarbonyl, 2,4,6-trimethylphenylcarbonyl;

optionally substituted aryloxycarbonyl such as p-nitrophenoxy-carbonyl;

aryl (Ci-C6) optionally substituted alkoxycarbonyl such as benzyloxycarbonyl or Cbz, p-methoxy-benzyloxycarbonyl, 3,4-dimethoxybenzyl-oxycarbonyl, o-nitrobenzyloxycarbonyl, p-nitrobenzyl-oxycarbonyl, 2-bromobenzyloxycarbonyl (2-bromo) and 2-chlorobenzyl-oxycarbonyl (2-chloro-Z), 4-nitrobenzyloxycarbonyl (nitro-Z), heteroaryl (Ci-C6) alkoxycarbonyl such as 9-fluorenylmethoxycarbonyl (FMOC) or nicotinoyl;

(di) (C1-C6) (alkyl) aminocarbonyl such as dimethylaminocarbonyl;

(C1-C6) (alkyl) arylaminocarbonyl;

carboxy;

optionally substituted aryl such as phenyl, dibenzosuberyl, or 1,3,5cycloheptatrienyl;

optionally substituted heteroaryl; including in particular the cationic or non-cationic heteroaryl, comprising from 1 to 4 following heteroatoms:

i) 5-, 6- or 7-membered monocyclics such as furanyl or furyl, pyrrolyl or pyrryl, thiophenyl or thienyl, pyrazolyl, oxazolyl, oxazolium, isoxazolyl, isoxazolium, thiazolyl, thiazolium, isothiazolyl, isothiazolium, 1,2,4-triazol 1,2,4-triazolium, 1,2,3triazolyle, 1,2,3-triazolium, 1,2,4-oxazolyle, 1,2,4-oxazolium, 1,2,4-thiadiazolyle, 1,2, 4thiadiazolium, pyrylium, thiopyridyl, pyridinium, pyrimidinyl, pyrimidinium, pyrazinyl, pyrazinium, pyridazinyl, pyridazinium, triazinyl, triazinium, tetrazinyl, tetrazinium, azepine, azepinium, oxazepinyl thiazide, epazinidinazepinyl, thiazide

ii) 8 to 11-membered bicyclics such as indolyl, indolinium, benzoimidazolyl, benzoimidazolium, benzoxazolyl, benzoxazolium, dihydrobenzoxazolinyl, benzothiazolyl, benzothiazolium, pyridoimidazolyl, pyridoimidazolium, thienocycloheptadienyl groups, or thienocycloheptadienic groups) C1-C4) alkyl as methyl, or polyhalo (C1-C4) alkyl as trifluoromethyl;

iii) or following tricyclic ABC:

in which the two rings A, Ç optionally comprise a heteroatom, and the ring B is a 5, 6 or 7-membered ring, particularly 6-membered and contains at least one heteroatom such as pypéridyle, pyranyl;

heterocycloalkyl optionally substituted, optionally cationic, the heterocycloalkyl group represents in particular a saturated or partially saturated monocyclic group with 5, 6 or 7 members comprising from 1 to 4 heteroatoms chosen from oxygen, sulfur and nitrogen, such as di / tetrahydrofuranyl , di / tetrahydrothiophenyl, di / tetrahydropyrrolyl, di / tetrahydropyranyl, di / tetra / hexahydrothiopyranyl, dihydropyridyl, piperazinyl, piperidinyl, tetramethylpiperidinyl, morpholinyl, di / tetra / hexahydroetyrin groups tetra / hexahydroazin) C1-C4) alkyl, oxo or thioxo preferably tetrahydropyranyl TH P; where the heterocycle represents the following grouping:

<\ _ (CR'eR '% in which R' ^c , R ' ^d , R' ^e , R ' ^f , R' ⁹ and R ' ^h , identical or different, represent a hydrogen atom or a group (Ci- C4) alkyl, or then two groups R ' ⁹ with R' ^h , and / or R ' ^e with R' ^f form an oxo or thioxo group, or else R ' ⁹ with R' ^e together form a cycloalkyl; and v represents an integer inclusive between 1 and 3; preferably R ' ^c to R' ^h represent a hydrogen atom; and An ^- represents a counterion;

isothiouronium -C (NR ' ^c R' ^d ) = N ⁺ R ' ^e R'^f; An ^- with R ' ^c , R' ^d , R ' ^e and R' ^f , identical or different, represent a hydrogen atom or a (Ci-C4) alkyl group; preferably R ' ^c to R' ^f represent a hydrogen atom; and Am represents a counterion;

isothiourea -C (NR ' ^c R' ^d ) = NR '^e; with R ' ^c , R' ^d and R ' ^e as defined above;

(di) aryl (Ci-C4) alkyl or triaryl (Ci-C4) optionally substituted alkyl such as 9-anthracenyl-methyl, phenylmethyl (benzyl), diphenylmethyl or triphenylmethyl optionally substituted by one or more groups chosen in particular from halogen, (Ci -C4) alkyl, (Ci-C4) alkoxy such as methoxy, hydroxy, (Ci-C4) alkylcarbonyl, (di) (Ci-C4) (alkyl) amino such as dimethylamino, nitro;

(di) heteroaryl (Ci-C4) akyl or triheteroaryl (Ci-C4) akyl optionally substituted, the heteroaryl group is in particular, cationic or not, monocyclic, comprising 5 or 6 members and from 1 to 4 heteroatoms chosen from nitrogen, oxygen and sulfur, such as pyrrolyl, furanyl, thiophenyl, pyridyl, pyridyl N-oxide such as 4-pyridyl or 2-pyridyl-N-oxide, pyrylium, pyridinium, triazinyl, optionally substituted by one or more group such as particularly methyl alkyl, advantageously the (di) heteroaryl (Ci-C4) akyle is (di) heteroarylmethyl or (di) heteroarylethyl;

CR ¹ R ² R ³ with R ¹ , R ² and R ³ identical or different, representing a halogen atom such as (tri) (di) halo (Ci-C4) alkyl such as 2,2,2-trichloroethyl or a group chosen from:

- (C1-C4) alkyl such as methyl;

- (Ci-C4) alkoxy;

- optionally substituted aryl such as phenyl optionally substituted by one or more groups such as (Ci-C4) alkyl, (Ci-C4) alkoxy, hydroxy;

- optionally substituted heteroaryl such as thiophenyl, furanyl, pyrrolyl, pyranyl, pyridyl, optionally substituted by a (Ci-C4) alkyl group;

- P (Z ¹ ) R ' ¹ R' ² R ' ³ with R' ¹ , and R ' ² identical or different represent a hydroxy group, (Ci-C4) alkoxy or alkyl, R' ³ represents a hydroxy group or ( CiC4) alkoxy, and Z ¹ represents an oxygen or sulfur atom;

(C2-Ce) alkytene in particular allyl H2C = CH-CH2-;

optionally substituted arylsulfonyl such as p-toluenesulfonyl (Tos);

sterically hindered cycloalkyl such as the adamantyl group;

sterically hindered cycloalkyloxy (thio) carbonyl such as 1-adamantyloxycarbonyl (Adoc) or 1- (adamantyl) -1-methylethoxy-carbonyl (Adpoc);

(Ci-C4) alkoxy (Ci-C4) optionally substituted alkyl such as methoxymethyl (MOM), ethoxyethyl (EOM) and isobutoxymethyl;

(tri) (di) halo (C1-C4) alkyl such as 2,2,2-trichloroethyl;

ReRfRgSi- with R _e , Rf, and R _g , identical or different, representing a (Ci-Ce) alkyl group, optionally substituted aryl, (di) aryl (Ci-C4) optionally substituted alkyl, triaryl (Ci-C4) alkyl optionally substituted, such as benzyl, in particular chosen from trimethylsilyl or TMS, triethylsilyl, isopropyldimethylsilyl, terbutyldimethylsilyl or TBDMS, (triphenylmethyl) dimethylsilyl, t-butyldiphenylsilyl, methyldiisopropylsilyl, methyl (di-silyl, di-silyl, di-silyl, diilyl triisopropylsilyl, triphenylsilyl;

or then two contiguous hydroxy groups can be protected by an alkylene group * -C (R ') (R ^m ) - (C (R ^k ) (R ^j )) g- * as drawn below:

with R ^j , R ^k , R ¹ , and R ^m , identical or different, representing a hydrogen atom or a (Ci-C4) alkyl, (poly) halo (Ci-C4) alkyl, optionally substituted aryl group such as phenyl, aryl (Ci-C4) alkyl such as benzyl, (poly) halo (Ci-C4) alkoxy, (Ci-C4) alkoxy, halogen, (di) (Ci-C4) (alkyl) amino, hydroxy, or so two groups R ^j and R ^k and / or R ¹ , and R ^m form together with the carbon atom which carry them an oxo group or a (hetero) clycloalkyl such as cyclohexyl or cyclopropyl; q is 0, 1, 2 or 3, preferably * -C (R ') (R ^m ) - (C (R ^k ) (R ^j )) q- * represents a methylene, ethylene, propylene, dimethylmethylene, * - C (CHs) 2- * or diphenylmethylene * -C (Ph) 2- *, cyclopentylidene, cyclohexylidene, cycloheptylidene, benzylidene, p-methoxybenzylidene, 2,4-dimethoxybenzylidene, methoxymethylene and ethoxymethylene by "hydrogen peroxide generating system" a chemical compound is understood which is not H2O2 but which can generate hydrogen peroxide and / or which contains hydrogen peroxide such as a) urea peroxide; b) polymer complexes capable of releasing hydrogen peroxide such as polyvinylpyrrolidone / H2O2 in particular in the form of powders and the other polymer complexes described in US 5,008,093; US 3,376,110; US 5,183,901; c) oxidases in the presence of a suitable substrate (for example glucose in the case of glucose oxidase or uric acid with uricase); d) metal peroxides generating hydrogen peroxide in water such as calcium peroxide, magnesium peroxide; e) perborates; or f) percarborates; in particular, they are chosen from a) urea peroxide, b) polymer complexes capable of releasing hydrogen peroxide chosen from polyvinylpyrrolidone / fUCk; c) oxidases; e) perborates and f) percarborates.

I- Use of at least one Compound of formula (I)

The subject of the invention is therefore the non-therapeutic cosmetic use of at least one compound of formula (I) as a whitening, lightening and / or depigmenting agent for keratin materials, in particular of the skin, said compounds corresponding to formula (I) ) next :

as well as its solvates such as hydrates, its optical, geometric isomers, tautomers and its base or acid salts, organic or inorganic, the formula (I) in which:

- S * denotes a monosaccharide sugar radical or denotes a polysaccharide sugar radical comprising from 2 to 5 saccharide unit (s), each saccharide unit (the saccharide unit in the case of a monosaccharide or each saccharide unit in the case of polysaccharides) comprising one or more hydroxy groups optionally substituted with a radical R 'chosen from:

i) (Ci-Ce) alkyl or (C2-Ce) alkenyl; or ii) an acety radical; or iii) a protective group (PG) of hydroxy function (s) such as (C2-C6) alkyl (thio) carbonyl or benzyl;

said monosaccharide radical being able, moreover, to be de-oxygenated in position 2 (on its carbon atom C2);

said monosaccharide or polysaccharide radical which may also comprise one or more amino groups NRbR _c with Rb and R _c , identical or different, representing a hydrogen atom, or an acety group, or a group protecting the amino function such as ( C2-C6) alkyl (thio) carbonyl;

said mono or polysaccharide radical being linked to the rest of the molecule by a bond between the carbon atom Ci of one of the sugars of said mono or polysaccharide radical, this bond possibly being anomeric a or β;

- R represents

i) a hydrogen atom;

ii) an (Ci-Cis) alkyl group;

iii) an aryl (Ci-C4) alkyl group, optionally substituted with at least one hydroxy and / or (Ci-C4) alkoxy group, such as benzyl;

iv) a cycloalkyl group,

Preferably the hydroxy radicals of the radical S * are not substituted or are all substituted by the same group R ’as defined above, in particular by an acetyl group.

Preferably the optional amino group (s) NRbRc of the radical S * denote (s) N H Rb with Rb denoting all a hydrogen atom or all an acetyl group.

More preferably, the hydroxy radicals of the radical S * are not substituted, and the optional amino group (s) NRbRc of the radical S * denote (s) NHRb with Rb all denoting a hydrogen atom or all an acetyl group.

According to a preferred form of the invention, the hydroxy radicals of the S * radical are not substituted, and the S * radical is not substituted by an amino radical NRbRc,

According to an advantageous embodiment, R represents

i) a hydrogen atom;

ii) a (Ci-Cis) alkyl group, in particular a (Ci-Ce) alkyl group and more particularly a (Ci-C4) alkyl group such as methyl;

It is understood that for the compounds of formula (I) as defined above when S * represents a monosaccharide radical then it may be in pyranose form (the sugar heterocycle which constitutes it is 6-membered) or furanose (the heterocycle sugar which constitutes it is 5-membered); and when S * represents a polysaccharide radical it comprises the chain of 2 to 5 identical or different saccharide units which may be in the form of furanose, or pyranose.

It is understood that for the compounds of formula (I) as defined above when S * represents a polysaccharide radical, preferably the polysaccharide is a disaccharide which results from the chain of 2 pyranose units or the chain of a saccharide unit in furanose form and of a unit in pyranose form or the chain of a saccharide unit in pyranose form and of a unit in furanose form;

whether for the monosaccharide or polysaccharide radical, each saccharide unit can be in the levorotatory L or dextrorotatory form, and in the anomeric form a or β.

According to a preferred embodiment, the sugar radical S * represents a monosaccharide radical of which the heterocycle which constitutes it contains 4 or 5 carbon atoms, of formula S * ’below:

R _a representing a hydrogen atom, a (Ci-C4) alkyl group such as methyl or a (poly) hydroxy (Ci-C4) alkyl group such as hydroxymethyl or dihydroxy-1,2-ethyl, the hydroxy function (s) of the poly) hydroxy (Ci-C4) alkyl group being substituted by A as defined below;

it being understood that the radical R _a is in position Cs if the sugar unit is in pyranose form or in C4 if it is in furanose form;

Rb representing a hydrogen atom or a (Ci-C4) alkyl group preferably hydrogen;

R _c representing a hydrogen atom, or a protecting group for the amine function such as Rd-C (X ') -, identical in the case of several hydroxyl functions, with X' representing an oxygen or sulfur atom, in in particular an oxygen atom and Rd representing a (Ci-C4) alkyl group, preferably R _c representing an acetyl group CHs-C (O) -,

R _e represents a hydrogen atom or a group -CH2-OA;

A representing a hydrogen atom, an (Ci-Ce) alkyl group, or a hydroxy protecting group such as Rd-C (X ') - as defined above and in particular acetyl CHs-C (O) -, or then when n is greater than or equal to 2 and two groups A-0 are contiguous then two groups A can together form a chain (Ci-Cejalkylène, linear or branched;

preferably, when A is different from a hydrogen atom and an (C1Ce) alkyl group, all the protective groups A are identical;

more preferably A represents a hydrogen atom, n is 1.2 or 3 and m is 0 or 1.

Preferably, m is 0.

According to another preferred embodiment, the sugar radical S * represents a polysaccharide radical consisting of 2 to 5 saccharide units, in particular 2 to 3, and preferably 2 saccharide units, linked together via an oxygen atom (oxy ) at 1-> 4 (Ci of a saccharide unit -> C4 of the other saccharide unit) or 1-> 3 (Ci of a saccharide unit -> C3 of the other saccharide unit) or 1-> 6 (Ci of a saccharide unit -> Ce of the other saccharide unit) in which each saccharide unit consists of a heterocycle comprising 4 or 5 carbon atoms, of formula S * ”below:

Formula S * ”in which p and q represent integers inclusive between 0 and 4 with p + q inclusive between 1 and 4, particularly between 1 and 2, preferably p + q = 1; R _a , identical or different, are as defined above, Rb, identical or different, are as defined above, R _c , identical or different, are as defined above, R _e , identical or different, are as defined above , A identical or different, are as defined above, m, identical or different, are as defined above, n, identical or different, are as defined above; it being understood that the two sugar patterns between the hooks q and p can be interchanged, ie represent the following sequence:

According to a preferred variant of the invention, the compounds of formula (I) are such that: - S * represents a monosaccharide sugar radical chosen from: glucose, galactose, mannose, xylose, lyxose, fucose, l arabinose, rhamnose, quinovose, fructose, sorbose, talose, 2-deoxyglucose, N-acetylglucosamine, N-acetylgalactosamine, glucosamine, galactosamine; or a disaccharide chosen from: lactose, maltulose, palatinose, lactulose, tonsillosis, turanose, cellobiose, isomaltose, rutinose, maltose; more preferably S * represents a monosaccharide sugar radical chosen from glucose, xylose, rhamnose, galactose or mannose; even more preferably S * represents a monosaccharide sugar radical chosen from glucose, xylose, rhamnose, galactose or mannose; even more preferably S * represents a monosaccharide sugar radical chosen from glucose, rhamnose or xylose, in particular glucose or xylose.

More preferably, the compounds of formula (I) are chosen from the compounds of formulas (I '), (I ”), (I” ”), (a), (l” a) and (l ”” a) following:

(the)

as well as their solvates such as hydrates, their optical, geometric isomers, tautomers and their salts,

Formulas (I ’), (I”), (I ””), (a), (l ”a) and (l” ”a) in which:

- R’i has the same definition as that of R for the compounds of formula (I); preferably R’i represents a hydrogen atom; or a (Ci-Ce) alkyl radical in particular (C1-C4) alkyl such as methyl;

- R’2 represents a hydrogen atom or the group -OR "with R" as defined below;

- R ”represents

i) (Ci-Ce) alkyl; or ii) an acety radical; or iii) a protective group (PG) of hydroxy function (s) such as (C2-C6) alkyl (thio) carbonyl or benzyl; or iv) a hydrogen atom;

Preferably R ”represents a hydrogen atom or an acety radical, and more particularly a hydrogen atom;

- R '”represents a hydrogen atom, or a (Ci-C4) alkyl group, or a group -CH2OR” with R ”as defined above in particular hydrogen or an acety radical, and preferably a hydrogen atom .

According to a particular embodiment, the compounds of the invention are of formula (I ’).

According to another particular embodiment of the invention, the compounds of the invention are of formula (I ”).

According to another particular embodiment of the invention, the compounds of the invention are of formula (I "").

According to another particular embodiment of the invention, the compounds of the invention are of formula (a).

According to another particular embodiment of the invention, the compounds of invention 5 have the formula (1 ”a).

According to another particular embodiment of the invention, the compounds of the invention are of formula (1 "" a).

According to a particular embodiment S * and S * 'represent a monosaccharide radical chosen from glucose, galactose, mannose, xylose, lyxose, fucose, arabinose, rhamnose, ribose, deoxy-ribose , lequinovose, fructose, sorbose, talose, 2-deoxyglucose, threose, erythrose, N-acetylglucosamine, N-acetylgalactosamine, glucosamine, galactosamine; in particular * and S * ’represent a monosaccharide radical chosen from glucose, xylose, rhamnose, galactose or mannose; even more particularly S * and S * ’represent a monosaccharide radical chosen from glucose, xylose, rhamnose; and even more particularly S * and S * ’represent a monosaccharide radical chosen from glucose or xylose.

In particular, S * and S * 'represent a monosaccharide radical chosen from D-glucose, D-gaitactose, D-mannose, D-xylose ₄ L-xylose, D-lyxose, L-lyxose, L-fucose, L-arabinose, D-arabinose, L-rhamnose, L-ribose, D-ribose, 2deoxy-D-ribose, 2-deoxy-L-ribose, D-quinovose, D-fructose, L-sorbose, D25 talose, 2-deoxy-D-glucose, D-threose, D-erythrose, L-threose, L-erythrose, N-acetyl-D- glucosamine, N-acetyl-D-galactosamine, D-glucosamine, D-galactosamine. Preferably, S * and S * 'denote a monosaccharide radical chosen from D-glucose, D-galactose, D-mannose, D-xylose, L-rhamnose; in particular, S * and S * 'represent a monosaccharide radical chosen from D-glucose, D-xylose, L-rhamnose, and more particularly a D-glucose or D-xylose radical.

According to another particular embodiment, S * and S * ”represent a polysaccharide radical and in particular a disaccharide radical chosen from lactose, maltulose, palatinose, lactulose, tonsillosis, leturanose, cellobiose, isomaltose, rutinose, maltose.

According to a particular form of the invention, S * and S * ”represent a polysaccharide radical, in particular a disaccharide radical chosen from lactose, maltose and cellobiose. In particular, S * and S * ”represent a disaccharide radical chosen from Dlactose, D-maltose, D-turanose and D-cellobiose.

As examples of new compounds of formula (I '), (I ”), (I” ”), (a), (l” a) and (l ”” a), according to the invention, there may be mentioned compounds 1a, 2a, 3a, and 4a, and 1 to 8, as well as their isomers, and / or their solvates and / or their salts and / or their tautomers:

and in particular the compounds 1, 2, 3, 4 and / or their solvates and / or their salts and / or their tautomers.

Acceptable solvates for the compounds used in the present invention include conventional solvates such as those formed in the last step of preparing said compounds due to the presence of solvents. By way of example, mention may be made of the solvates due to the presence of water (hydrates) or of linear or branched alcohols such as ethanol or isopropanol.

The salts of the compounds of formula (I) which comprise at least one amine function can be salts of organic acid such as citric acid, lactic acid, tartaric acid, aspartic acid, glutamic acid, acetic acid, formic acid, acid trifluoroacetic, hydrochloric acid, glycolic acid, or malic acid;

The salts of the compounds of formula (I) which comprise at least one acid function can also be chosen from metal salts, for example aluminum (Al ³⁺ ), zinc (Zn ²⁺ ), manganese (Mn ²⁺ ) or copper ( Cu ²⁺ ), alkaline salts, for example lithium (Li ⁺ ), sodium (Na ⁺ ) or potassium (K ⁺ ), or alkaline earth, for example calcium (Ca ²⁺ ) or magnesium (Mg ²⁺ ). It can also be ammonium derivatives of formula NHV or organic salts such as ammoniums of formula Y3NIT, NY3 denoting an organic amine, the radicals Y being identical or different, two or three radicals Y being able to form a ring in pairs with the nitrogen atom which carries them or NY3 can designate an aromatic amine. The organic amines are, for example, alkylamines, such as for example methylamine, dimethylamine, trimethylamine, triethylamine or ethylamine, or hydroxyalkylamines, such as, for example, 2-hydroxyethylamine, bis- (2-hydroxyethyl) amine or tri- (2-hydroxyethyl) amine, or cycloalkylamines, such as for example bicyclohexylamine or glucamine, piperidine, or pyridines and the like, for example collidine, quinine or quinoline, or basic amino acids , such as lysine or arginine. In the case where the compounds according to the invention are in the form of a salt, the anions or the cations are of course present in an amount ensuring the electroneutrality of the compounds of formula (I).

The salts of the compounds of formula (I) according to the invention which comprise at least one acid function can be advantageously chosen from the metal salts Cu ²⁺ , Mn ²⁺ and Zn ²⁺ , the alkaline salts Li ⁺ , Na ⁺ and K ⁺ and the alkaline earth salts Ca ²⁺ and Mg ²⁺ .

According to another variant, the salts of the compounds of formula (I) according to the invention which comprise at least one acid function can be advantageously chosen from ammoniums, preferably from amino acid salts of basic character such as for example lysine or arginine or from the salts of diethanolamine or triethanolamine.

Il- New compounds

The invention also relates to the compounds of formula (I) as defined above,

In particular, the subject of the invention is the new compounds of formulas (I '), (I ”), (I” ”), (a), (l” a) and (l ”” a), such as defined below.

The preferred new compounds are compounds 1a, 2a, 3a, and 4a, and 1 to 8 described above.

III. Obtaining the compounds C-glycosides 5-oxazolidine-2 ₁ 4-diones

1) Process for the Synthesis of New Compounds of Formula (I)

Another object of the invention is a process for the preparation, or process for the chemical synthesis of the compounds of formula (I) as defined above according to the following scheme (1):

in which (II) denotes a monosaccharide represented by:

H or a PS-OH polysaccharide in which, A, R _a , Rb, Rc, Re, n, and m are as defined above, p 'and q' representing an integer inclusive between 0 and

4, with p ’+ q’ which is inclusive between 0 and 4, in particular between 0 and 2, preferably p ’+ q’ = 0 or 1, it being understood that the two patterns in square brackets can be interchanged; PS-OH denoting a polysaccharide with the following structure (gg):

p'i— —iq '(gg) step 1 consisting in reacting a monosaccharide or a polysaccharide PS-OH of formula (II) with a derivative of barbituric acid (III), in particular in the presence of a mineral base such that ΜΌΗ ', M ⁺ representing a cationic counter ion, or preferably a weak base such as (bi) carbonate, in particular with (bi) carbonate of alkali metal, or in the presence of an organic base such as triethylamine or diisopropylethylamine;

in particular in a polar protic solvent such as water, optionally heating to a temperature between 30 ° C and 100 ° C, in particular to 80 ° C, preferably for a period of between 1 hour and 24 hours, in especially between 3 am and 10 am, such as 5 am; to lead to the compound with a sugar motif (IV);

step 2 consisting in reacting the compound (IV) with a chemical oxidizing agent such as hydrogen peroxide or a hydrogen peroxide generating agent such as oxone or also a biological agent such as an enzyme oxidase type, in particular in a polar solvent (or mixture of solvents) with a boiling point between 40 ° C and 100 ° C at atmospheric pressure, such as acetone or acetonitrile, or polar protic solvent such as l water optionally in a basic medium and / or in the presence of a chelating agent such as ethylene diamine tetraacetic acid (EDTA) in the form of a salt or not, to yield a C-glycoside compound (I) according to the invention, it being understood that if A represents a hydrogen atom and it is desired to have a protective group PG then a protection step is added, that if Rb and R _c of NRbRc possibly present on the monosaccharide or the polysaccharide (II) represent hydrogen atoms and that it is t desired to protect the amino group (s), a protection step is carried out, that if the group R has a function sensitive to these synthesis steps, a protection / deprotection sequence should be added,

Under certain temperature and reaction time conditions during step 2, it is possible to isolate the intermediate (V) according to step 2a:

R

I

Ο (iv)

Step 2b consists in treating the compound (V) in a polar solvent (or mixture of solvents) with a boiling point of between 40 ° C. and 100 ° C. at atmospheric pressure, such as acetone or acetonitrile , or polar protic solvent such as water, optionally in a basic medium, in particular by adding a mineral base such as sodium hydroxide or potassium hydroxide, and / or in the presence of a chelating agent such as ethylene diamine tetraacetic acid (EDTA) in the form salt or not, and optionally in the presence of a chemical oxidizing agent such as hydrogen peroxide or a hydrogen peroxide generating agent such as oxone or a biological agent such as an oxidase type enzyme , to lead to a C-glycoside compound (I) according to the invention.

The compounds of formula (V), as well as their solvates and / or isomers and / or salts, are new. They can also be represented by the general formula below

R

With S * and R as described above.

The invention also relates to the compounds of formula (V).

Thus, when the process described above implements D-glucose, it is possible to isolate after step 1, then step 2 of oxidation, carried out for a limited time, the new compound 9 (and / or its solvates and / or its salts):

All the reagents are obtained by conventional methods known to those skilled in the art. In particular, the compounds (III) are commercial or can be prepared, for example by the following method:

/ NH, R ²

(VII) (VI)

The amines (VI) are reacted with the isocyanates (VII) to form symmetrical urea, which then reacts with an activated malonyl derivative (VIII), such as malonyl chloride (Y = Cl), to lead to the compounds (III), the reaction taking place in a polar aprotic solvent such as dichloromethane, THF, ether, or acetonitrile, at temperatures ranging from 20 ° C. to 160 ° C.

Those skilled in the art will take care to protect or unprotect sensitive functions according to the synthesis steps.

As compounds of formula (I), in particular (I '), (I ”), (I” ”), (a), (l” a) and (l ”” a) ,, the compounds la, 2a, 3a, and 4a, and 1 to 8 described above.

IV - Compositions

The compounds of formula (I) according to the invention find a very particular application in the cosmetic field.

A subject of the invention is also a composition containing at least one compound of formula (I), and preferably at least one compound of formula (I '), (I ”), (I” ”), (a) , (l ”a) and (l” ”a) defined above, and more particularly at least one compound 1a, 2a, 3a, and 4a, and 1 to 8 as defined above.

The composition according to the invention is advantageously a cosmetic composition. The composition according to the invention is advantageously a composition intended for topical application.

The composition according to the invention advantageously comprises, in a physiologically acceptable medium, at least one compound of formula (I) as described above, and preferably at least one compound of (I '), (I ”), (I” ”), (A), (l” a) and (l ”” a) defined above, and more particularly at least one compound 1a, 2a, 3a, and 4a, and 1 to 8 as defined above .

By physiologically acceptable medium is meant a medium compatible with human keratin materials such as the skin of the body or of the face, the lips, the mucous membranes, the eyelashes, the nails, the scalp and / or the hair.

The compound of formula (I), and in particular the compound of (I '), (I ”), (I” ”), (a), (l” a) and (l ”” a) or even 1a , 2a, 3a, and 4a, and 1 to 8_defined above, (each compound of formula (I) and in particular each compound of formula (I '), (I ”), (I” ”), (a ), (l ”a) and (l” ”a) and more particularly a compound 1a, 2a, 3a, and 4a, and 1 to 8 if the composition comprises several) may be present in the composition according to the invention, in an amount which can be between 0.01 and 10% by weight, preferably between 0.1 to 5% by weight, in particular between 0.5 to 3% by weight, relative to the total weight of the composition.

The composition according to the invention is advantageously a cosmetic composition: it can comprise adjuvants usually used in the cosmetic field. The composition can be an aqueous composition, that is to say containing water or a mixture of water and water-miscible solvents such as C2-C6 alcohols.

Mention may in particular be made of; organic solvents, in particular C2-C6 alcohols; oils, in particular hydrocarbon oils, silicone oils; waxes, pigs, fillers, dyes, surfactants, emulsifiers; cosmetic active ingredients, polymers, thickeners, preservatives, perfumes, bactericides, odor absorbers, antioxidants.

According to an advantageous form of the invention, the cosmetic composition contains at least one compound of formula (I), and in particular at least one compound of formula (I '), (I ”), (I” ”), (l a), (l ”a) and (l” ”a), as defined above and at least one additive chosen from perfumes, oils, waxes, surfactants, thickeners, dyes, bactericides, conservatives.

In a preferred embodiment, the cosmetic composition according to the invention contains at least one compound chosen from compounds 1a, 2a, 3a, and 4a, and 1 to 8 defined above, as well as their solvates such as hydrates, and their salts. base or acid, organic or mineral.

These optional cosmetic adjuvants may be present in the composition in an amount of 0.001 to 80% by weight, in particular 0.1 to 40% by weight, relative to the total weight of the composition. In any event, these adjuvants, as well as their proportions, will be chosen by a person skilled in the art so that the advantageous properties of the compounds according to the invention are not, or not substantially, altered by the addition envisaged.

As active agents, it will be advantageous to introduce into the composition according to the invention at least one compound chosen from: desquamating agents; soothing agents, organic or inorganic photoprotective agents, moisturizing agents; depigmenting agents other than those which are the subject of the present invention; anti-glycation agents; NO synthase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; dermo-relaxing agents; tensing agents; anti-pollution and / or anti-radical agents; agents acting on the microcirculation; ceramides; agents acting on the energy metabolism of cells; and their mixtures.

The composition according to the invention may in particular be presented in all the galenical forms normally used in the cosmetic field, and in particular in the form of an aqueous or hydroalcoholic solution, optionally gelled, of a dispersion of the lotion type, optionally biphasic, of an oil-in-water or water-oil or multiple emulsion ((W / O / W or O / W / W for example), of an aqueous gel, of an oil dispersion in an aqueous phase with using spherules, these spherules possibly being polymeric nanoparticles such as nanospheres and nanocapsules or, better still, lipid vesicles of ionic and / or nonionic type, of aqueous or oily gel. These compositions are prepared according to the usual methods. composition according to the invention may constitute a skin care composition, and in particular a cream for cleansing, protecting, treating or caring for the face, for the hands, for the feet, for large folds anatomical or for the body (for example day creams, night creams, makeup remover creams, foundation creams, sunscreen creams); a fluid foundation, a cleansing milk, a body milk for protection or care, an anti-sun milk; a skin care lotion, gel or foam, such as a cleansing lotion.

V · Treatment process

The subject of the invention is also a method of cosmetic treatment of the skin, comprising the application to the skin, of a composition comprising at least one compound of formula (I), and preferably at least one compound of formula (I '), (I ”), (I” ”), (a), (l” a) and (l ”” a) defined above, and more particularly at least one compound 1a, 2a, 3a, and 4a, and 1 to 8 as defined above.

The subject of the invention is also a non-therapeutic cosmetic process for depigmentation, lightening and / or bleaching of keratin materials, in particular of the skin, comprising the application of the cosmetic composition described above comprising at least one compound of formula ( I) and preferably at least one compound of formula (I '), (I ”), (I” ”), (a), (l” a) and (l ”” a) defined above, and more particularly at least one compound 1a, 2a, 3a, and 4a, and 1 to 8 as defined above.

More preferably, it is the process for depigmenting, lightening and / or bleaching the skin.

The invention also relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined above, and preferably at least one compound of formula (I '), (I ”), (I” ” ), (a), (l ”a) and (l” ”a) defined above, and more particularly at least one compound 1a, 2a, 3a, and 4a, and 1 to 8_as defined above, as whitening, lightening and / or depigmenting agent for keratin materials, in particular for the skin.

The different examples below describe different synthetic routes making it possible to obtain the compounds of formula (I).

In these diagrams "t.a. "Means room temperature.

The invention is illustrated in more detail by the following nonlimiting examples.

EXAMPLES

A) Examples of synthesis

4.1 Synthesis of compounds 1, 2, 3, 4 and 9

Example 1: Synthesis of Compound 1

barbituric acid

1.2 eq

NaHCO ₃ , H ₂ O ° C, 5 h

50% H ₂ O ₂ (2 eq)

H ₂ O, 70 ° C, 4.5h

compound 1

Step 1. To a solution of D-glucose (15 g, 83 mmol) in water (170 mL), barbituric acid (10.7 g, 83 mmol) is added with stirring, then NaHCOs is added until pH 7. After neutralization, the mixture is heated at 80 ° C for 5 h. The reaction is followed by TLC in Dichloromethane / MeOH 6: 4 + 1% acetic acid. The reaction mixture is added dropwise to acetone (850 mL) with vigorous stirring. The precipitate obtained is filtered then washed 3 times in acetone, and the solid 10 obtained is dried under vacuum. It is isolated as a yellow powder. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

Step 2. To a solution of compound 10 (21.4 g, 68.5 mmol) in water (60 mL) is added 50% hydrogen peroxide (137 mmol) with stirring. The reaction mixture is brought to 70 ° C. for 4 h 30 min. The reaction is followed by TLC (BuOH / fW / AcOH 6: 2: 2). The mixture is then added dropwise to rt in 600 ml of acetone. The residue formed is filtered, then dissolved in water and the solution concentrated to dryness. The powder obtained is washed twice in acetone, to yield compound 1 in the form of a pale yellow powder. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

Example 2 Synthesis of Compound 2

1.2 eq

30% H ₂ O ₂ (2 eq)

H ₂ O, Tue, 4 p.m.

compound 2

Step 1. According to the process described in Example 1, intermediate 11 is obtained from D-xylose and barbituric acid. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure 11.

Step 2. In a 100 ml three-necked flask equipped with a refrigerant, an argon inlet, a bubbler, a thermometer and a magnetic stirrer, 15 g of 11 were placed (0.053 moles) in 35 ml of water. 10.9 ml of 30% hydrogen peroxide in water (0.106 moles) were then added. The reaction medium is stirred at ambient temperature, following the reaction by TLC water / acetonitrile 8: 2.

After one night of stirring, the starting product is consumed but the peroxide test is positive. The reaction medium is heated at 80 ° C for 3 hours (negative peroxide test), cooled to room temperature then poured into a flask containing 250 ml of ethanol before being concentrated to dryness on a rotary evaporator.

The paste obtained is taken up in a mortar and with acetone to yield compound 2 in the form of a light beige powder. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

Example 3 Synthesis of Compound 3

D-alucose 1,3-dimethylbarbituric acid

1.2 eq

NaHCO ₃ , H ₂ O ° C, 5 h

oxone, EDTANa ^ NaHCO ₃ ,

CH ₃ CN, Me ₂ CO, ta, 4 p.m.

compound 3

Step 1. According to the method described in Example 1, intermediate 12 is obtained from D-glucose and 1,3-dimethylbarbituric acid. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure 12.

Step 2. To a solution of 12 (10.0 g, 32.0 mmol) in 140 mL of acetonitrile is added an aqueous solution of EDTANa2 (13 mg in 90 mL of water, C = 4.10 ' ⁴ M, 0.036 mmol) with stirring . After a few minutes, the mixture is cooled in an ice bath and then 25 ml of acetone are added. Then is slowly added an oxone (48.0 g, 78.1 mmol) / NaHCOs (20.0 g, 238 mmol) mixture. Stirring is continued overnight at ta then the reaction mixture is filtered. After evaporation under vacuum, the residue is taken up in methanol, and the insoluble material is filtered. The filtrate is evaporated under vacuum and then purified on silica gel (dichloromethane / MeOH 8: 2). Compound 3 is obtained in the form of a white solid. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

Example 4 Synthesis of Compound 4

Step 1. According to the process described in Example 1, intermediate 13 is obtained from L-rhamnose and 1,3-dimethylbarbituric acid. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure 13.

Step 2. To a solution of 13 (5.0 g, 15.4 mmol) in 80 mL of acetonitrile is added an aqueous solution of EDTANa2 (7 mg in 46 mL of water, 0.019 mmol) with stirring. After a few minutes, the mixture is cooled in ice and then 13 ml of acetone are added. Then is gently added an oxone (25.2 g, 41.0 mmol) / NaHCOs (10.5 g, 125 mmol) mixture at the rate of approximately 2/3 of a spatula every 10 min. The pH is stabilized at around 7.3. Stirring is continued overnight at ta then the reaction mixture is filtered. After evaporation under vacuum, the residue is purified on silica gel by elution of an increasing gradient of MeOH in dichloromethane. Compound 4 is obtained in the form of a yellow oil. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

Example 5 Synthesis of Compound 9

oxone, EDTANa ₂ , NaHCO ₃ ,

CH ₃ CN, Me ₂ CO, ta, 2 hrs

OH compound 9

To a solution of 12 (100 mg, 0.294 mmol) in 1.5 mL of acetonitrile is added an aqueous solution of EDTANa2 (0.4 mM, 1 mL, 0.35 μηηοΙ) with stirring. After a few minutes, the mixture is cooled in ice and then 0.26 ml of acetone are added. Then gently added at once in an oxone (0.5 g, 0.814 mmol) / NaHCOs (0.2 g, 2.38 mmol) mixture. The pH is stabilized at around 8. After 2 h of stirring, the reaction mixture is filtered and concentrated under vacuum to obtain 70 mg of compound 9 in the form of a white paste. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure 9.

B) Demonstration of depigmenting activity

The measurement of the depigmenting activity (reduction in the production of melanin) of compounds of formula (I) was carried out by assaying normal human melanocytes in vitro as follows.

First, normal human melanoycts are grown and distributed in wells. After 24 hours, the culture medium was replaced by a medium containing compounds of formula (I) to be evaluated. The cells were incubated 72 hours before the measurement of the final optical density which measures the quantity of melanin produced by the melanocytes. The compounds are tested at 100 μΜ after calibration. Lucinol (n-butyl resorcinol) at 100 μΜ is used as a positive reference, and corresponds to 100% of depigmentation.

Compound No. % depigmentation at 100 μΜ 1 34% 2 39% 3 37%

The compounds of formula (I) have shown a depigmenting effect.

Example 3 Cosmetic Composition

A depigmenting composition for the skin is prepared comprising (in grams):

Compound # 2 2g

PEG400 68 g

Ethanol 30 g

The composition applied to the skin helps to remove dark spots.

A similar composition is prepared with compound 3

Example 4: gel

A depigmenting gel for the skin is prepared comprising (% by weight):

Compound # 2 0.25%

Carbomer (Carbopol 981 from Lubrizol) 1% preservative qs water qs 100%

The composition applied to the skin helps to remove dark spots.

A similar composition is prepared with compound 3

Claims (10)

1. Non-therapeutic cosmetic process for depigmentation, lightening and / or bleaching of keratin materials, comprising the application of a compound of formula (I) or of a composition comprising one or more compounds of formula (I): as well as their solvates such as hydrates, their optical, geometric, tautomeric isomers and their base or acid salts, organic or inorganic,

formula (I) in which: - S * denotes a monosaccharide sugar radical or denotes a polysaccharide sugar radical comprising from 2 to 5 saccharide unit (s), each saccharide unit (the saccharide unit in the case of a monosaccharide or each saccharide unit in the case of polysaccharides) comprising one or more hydroxy groups optionally substituted with a radical R 'chosen from: i) (Ci-Ce) alkyl or (C2-Ce) alkenyl; or ii) an acetyl radical; or iii) a protective group (PG) of hydroxy function (s) such as (C2-C6) alkyl (thio) carbonyl or benzyl; said monosaccharide radical being able, moreover, to be de-oxygenated in position 2 (on its carbon atom C2); said monosaccharide or polysaccharide radical which may also comprise one or more amino groups NRbRc with Rb and R _c , identical or different, representing a hydrogen atom, or an acetyl group, or a group protecting the amino function such as (C2 C6) alkyl (thio) carbonyl; said mono or polysaccharide radical being linked to the rest of the molecule by a bond between the carbon atom Ci of one of the sugars of said mono or polysaccharide radical, this bond possibly being anomeric alpha or beta; - R represents i) a hydrogen atom; ii) an (Ci-Cis) alkyl group; Iii) an aryl (Ci-C4) alkyl group, optionally substituted with at least one hydroxy and / or (Ci-C4) alkoxy group, such as benzyl; iv) a cycloalkyl group. 2. Method according to the preceding claim wherein the compound (s) of form- 10 mule (I) comprises (s) a radical R chosen from: i) a hydrogen atom; ii) an (Ci-Cis) alkyl group, in particular a (Ci-Ce) alkyl group and more particularly a (Ci-C4) alkyl group such as methyl. 15 3. Method according to any one of the preceding claims, in which the compound (s) of formula (I) comprises (s) a sugar radical S * which represents a monosaccharide radical in which the heterocycle which constitutes it contains 4 or 5 carbon atoms, of the following formula S * ':

R _a representing a hydrogen atom, a (Ci-C4) alkyl group such as methyl or a (poly) hydroxy (Ci-C4) alkyl group such as hydroxymethyl or dihydroxy-1,2-ethyl, the hydroxy function (s) of the poly) hydroxy (Ci-C4) alkyl group being substituted by A as defined below; it being understood that the radical R _a is in position Cs if the sugar unit is in pyranose form or in C4 if it is in furanose form; Rb representing a hydrogen atom or a (Ci-C4) alkyl group preferably hydrogen; R _c representing a hydrogen atom, or a protecting group for the amine function such as Rd-C (X ') -, identical in the case of several hydroxyl functions, with X' representing an oxygen or sulfur atom, in in particular an oxygen atom and Rd representing a (Ci-C4) alkyl group, preferably R _c representing an acetyl group CHs-C (O) -, R _e represents a hydrogen atom or a group -CH2-OA; A representing a hydrogen atom, a (Ci-Ce) alkyl group, or a protective group of hydroxy function, or then when n is greater than or equal to 2 and that two groups A-0 are contiguous then two groups A can form together a linear or branched (Ci-Ce) alkylene chain; preferably when A is other than a hydrogen atom and a (C1C6) alkyl group or the protecting groups of A are identical; n is 1.2 or 3 and m is 0 or 1, preferably m is 0. 4. Method according to any one of claims 1 to 3 wherein the compound (s) ^) of formula (I) comprises (s) a sugar radical S * which represents a polysaccharide radical consisting of 2 to 5 saccharide units, in particular of 2 to 3, and preferably 2 saccharide units, linked together via an oxygen atom (oxy) in 1-> 4 (Ci of a saccharide unit -> C4 of the other saccharide unit) or 1-> 3 (Ci of a saccharide unit -> C3 of the other saccharide unit) or 1-> 6 (Ci of a saccharide unit -> Ce of the other saccharide unit) in which each saccharide unit consists of a heterocycle comprising 4 or 5 carbon atoms, of formula S * ”below:

Formula S * ”in which: - p and q, represent integers inclusive between 0 and 4 with p + q inclusive between 1 and 4, particularly between 1 and 2, preferably p + q = 1; - R _a , Rb, Rc, Re, A m, and n, identical or different, are as defined in any one of the preceding claims; it being understood that the two sugar patterns between the hooks q and p can be interchanged, ie represent the following sequence:

5. Method according to any one of claims 1 to 3 wherein the compound (s) ^) of formula (I) comprises (s) a sugar radical S * or S * 'which represents a monosaccharide radical chosen from glucose, galactose, mannose, xylose, lyxose, fucose, arabinose, rhamnose, ribose, deoxy-ribose, quinovose, fructose, sorbose, talose, 2-deoxyglucose threose, erythrosis, N-acetylglucosamine, N-acetylgalactosamine, glucosamine, galactosamine; in particular, S * or S * 'represents a monosaccharide radical chosen from D-glucose, D-galactose, Dmannose, D-xylose, L-xylose, D-lyxose, L-lyxose, L -fucose, L-arabinose, D-arabinose, L-rhamnose, L-ribose, D-ribose, 2-deoxy-D-ribose, 2-deoxy-Lribose, D-quinovose, D -fructose, L-sorbose, D-talose, 2-deoxy-D-glucose, D-threose, D-erythrose, L-threose, L-erythrose, N-acetyl-D-glucosamine , Nacetyl- D-galactosamine, D-glucosamine, D-galactosamine. Preferably, S * or S * 'denotes a monosaccharide radical chosen from D-glucose, D-galactose, Dmannose, D-xylose, D-lyxose, L-fucose, L-arabinose, L- rhamnose, D-ribose, 2-deoxy-D-ribose, D-quinovose, D-fructose, L-sorbose, D-talose, 2-deoxyD-glucose, D-threose, D -erythrosis, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-glucosamine, D-galactosamine; advantageously, chosen from glucose, xylose, rhamnose, mannose and galactose; in particular, S * or S * 'denotes a monosaccharide radical chosen from D-glucose, D-xylose, L-rhamnose, D-mannose, D-galactose in particular, S * and S *' represent a monosaccharide radical chosen from D-glucose, D-xylose, L-rhamnose, and more particularly a D-glucose or D-xylose radical. 6. Method according to any one of claims 1 to 3 and 5 wherein the compound (s) of formula (I) comprises (s) a sugar radical S * or S * 'which represents a monosaccharide radical chosen from glucose, xylose and rhamnose; particularly, S * or S * 'denotes a sugar radical chosen from D-glucose, D-xylose and Lrhamnose, more particularly, S * or S *' denotes a glucose or xylose radical, preferably S * or S * 'denote a D-glucose or D-xylose radical. 7. Method according to any one of claims 1 to 4 wherein the compound (s) of formula (I) comprises (s) a sugar radical S * or S * ”which represents a polysaccharide radical and in particular a disaccharide radical of preferably chosen from lactose, maltulose, palatinose, lactulose, tonsillosis, turanose, cellobiose, isomaltose, rutinose, maltose; more particularly chosen from Dlactose, maltulose, palatinose, lactulose, tonsillosis, D-turanose, D-cellobiose, isomaltose, rutinose, D-maltose, in particular a disaccharide radical chosen from lactose, maltose and cellobiose. In particular, S * and S * ”represent a disaccharide radical chosen from D-lactose, D-maltose and D-cellobiose. 8. Method according to any one of the preceding claims in la- 5 which the compound (s) of formula (I) are chosen from the compounds of formula (I '), (I ”), (I” ”), (a), (l” a) and ( l ”” a) following:

from) to) GOLD

as well as their solvates such as hydrates, their optical, geometric isomers, tautomers and their salts, Formulas (I ’), (I”), (I ””), (a), (l ”a) and (l” ”a) in which: - R’i has the same definition as that of R for the compounds of formula (I); preferably R’i represents a hydrogen atom; or a (Ci-Ce) alkyl radical in particular (C1-C4) alkyl such as methyl; - R’2 represents a hydrogen atom or the group -OR "with R" as defined below; - R ”represents i) (Ci-Ce) alkyl; or ii) an acetyl radical; or iii) a protective group (PG) of hydroxy function (s) such as (C2-C6) alkyl (thio) carbonyl or benzyl; or iv) a hydrogen atom; Preferably R ”represents a hydrogen atom or an acetyl radical, and more particularly a hydrogen atom; - R '”represents a hydrogen atom, or a (Ci-C4) alkyl group, or a group -CH2OR” with R ”as defined above in particular hydrogen or an acetyl radical, and preferably a hydrogen atom . 9. Method according to any one of the preceding claims, in which the compound or compounds of formula (I) are chosen from the following compounds: compound structure

compound sugar structure

as well as their solvates such as hydrates, and their base or acid salts, organic or inorganic. 10. Composition comprising one or more compounds of formula (I) as defined in any one of the preceding claims, preferably at least one compound of formula (I) chosen from (I '), (I ”), ( I ””), (a), (l ”a) and (l” ”a) as defined in claim 8 and compounds 1a, 1b, 1c, 1d and 1 to 8 as defined in the preceding claim . 11. Composition according to claim 10, wherein the compound or compounds of formula (I) are present in amounts ranging from 0.01 to 10% by weight, preferably from 0.1 to 5% by weight relative to the total weight of the composition. 15 12.. Composition according to one of Claims 10 to 11, characterized in that it comprises at least one adjuvant chosen from the group formed by organic solvents, in particular C2-C6 alcohols; oils, in particular hydrocarbon oils, silicone oils; waxes, pigments, fillers, dyes, surfactants, emulsifiers; cosmetic active ingredients, organic or inorganic photoprotective agents, polymers, thickeners, preservatives, perfumes, bactericides, ceramides, odor absorbers, antioxidants. 13 .. Compounds of formula (I) as well as their solvates such as hydrates, their optical, geometric isomers, tautomers and their base or acid salts, organic or inorganic,

formula (I) in which: - S * denotes a monosaccharide sugar radical or denotes a polysaccharide sugar radical comprising from 2 to 5 saccharide unit (s), each saccharide unit (the saccharide unit in the case of a monosaccharide or each saccharide unit in the case of polysaccharides) comprising one or more hydroxy groups optionally substituted with a radical R 'chosen from: i) (Ci-Ce) alkyl or (C2-Ce) alkenyl; or ii) an acetyl radical; or iii) a protective group (PG) of hydroxy function (s) such as (C2-C6) alkyl (thio) carbonyl or benzyl; said monosaccharide radical being able, moreover, to be de-oxygenated in position 2 (on its carbon atom C2); said monosaccharide or polysaccharide radical which may also comprise one or more amino groups NRbRc with Rb and R _c , identical or different, representing a hydrogen atom, or an acetyl group, or a group protecting the amino function such as (C2 C6) alkyl (thio) carbonyl; said mono or polysaccharide radical being linked to the rest of the molecule by a bond between the carbon atom Ci of one of the sugars of said mono or polysaccharide radical, this bond possibly being anomeric alpha or beta; - R represents i) a hydrogen atom; ii) an (Ci-Cis) alkyl group; iii) an aryl (Ci-C4) alkyl group, optionally substituted with at least one hydroxy and / or (Ci-C4) alkoxy group, such as benzyl; iv) a cycloalkyl group. 14. -. Compound of formula (I) according to the preceding claim comprising a radical R chosen from: i) a hydrogen atom; ii) an (Ci-Cis) alkyl group, in particular a (Ci-Ce) alkyl group and more particularly a (Ci-C4) alkyl group such as methyl. 15. Method according to any one of claims 1 to 9, for depigmenting, lightening and / or bleaching the skin. 16. Non-therapeutic cosmetic use of a compound of formula (I) as defined in any one of claims 1 to 8, and compounds 1a, 2a, 3a, and 4a, and 1 to 8_as defined in claim 9 , as a whitening, lightening and / or depigmenting agent for keratin materials, in particular the skin. 17. Process for the synthesis of compound of formula (I) as defined in any one of claims 1 to 9 according to the following scheme (1):

in which (II) denotes a monosaccharide represented by:

5 or a polysaccharide PS-OH in which, A, R _a , Rb, Rc, Re, n, and m are as defined above, p 'and q' representing an integer inclusive between 0 and 4, with p '+ q 'which is inclusive between 0 and 4, in particular between 0 and 2, preferably p' + q '= 0 or 1, it being understood that the two patterns in square brackets can be interchanged; PS-OH denoting a polysaccharide with the following structure (gg):

10 ^ - ¹ P ' ¹ - - d' (gg) step 1 consisting in reacting a monosaccharide or a polysaccharide PS-OH of formula (II) with a derivative of barbituric acid (III), in particular in the presence of mineral base such as ΜΌΗ ', M ⁺ representing a cationic counter ion, or preferably a weak base such as (bi) carbonate, in particular with (bi) carbonate of alkali metal, or in the presence of organic base such as triethylamine or diisopropylethylamine; in particular in a polar protic solvent such as water, optionally heating to a temperature between 30 ° C and 100 ° C, in particular to 80 ° C, preferably for a period of between 1 hour and 24 hours, in especially between 3 am and 10 am, such as 5 am; to lead to the compound with a sugar motif (IV); step 2 consisting in reacting the compound (IV) with a chemical oxidizing agent such as hydrogen peroxide or a hydrogen peroxide generating agent such as oxone or also a biological agent such as an enzyme oxidase type, in particular in a polar solvent (or mixture of solvents) with a boiling point between 40 ° C and 100 ° C at atmospheric pressure, such as acetone or acetonitrile, or polar protic solvent such as l water optionally in a basic medium and / or in the presence of a chelating agent such as ethylene diamine tetraacetic acid (EDTA) in the form of a salt or not, to yield a C-glycoside compound (I) according to the invention, it being understood that if A represents a hydrogen atom and it is desired to have a protective group PG then a protection step is added, only if Rb and R _c of NRbR _c possibly present on the monosaccharide or the polysaccharide (II) represent hydrogen atoms and that it e st is desired to protect the amino group (s) a protection step is carried out, that if the group R has a function sensitive to these synthesis steps, a protection / deprotection sequence should be added, Under certain temperature and reaction time conditions during step 2, it is possible to isolate the intermediate (V) according to step 2a:

Step 2b consists in treating the compound (V) in a polar solvent (or mixture of solvents) with a boiling point between 40 ° C and 100 ° C at atmospheric pressure, such as acetone or acetonitrile, or polar protic solvent such as water, optionally in a basic medium, in particular by adding a mineral base such as sodium hydroxide or potassium hydroxide, and / or in the presence of a chelator such as ethylene diamine tetraacetic acid (EDTA) in the form of salt or not, and optionally in the presence of a chemical oxidizing agent such as hydrogen peroxide or a hydrogen peroxide generating agent such as oxone or also a biological agent such as an oxidase type enzyme, for lead to a C-glycoside compound (I) according to the invention. 18. Compounds of formula (V), as well as their solvates and / or isomers and / or salts, of general formula below

With S * and R as described in claims 1 to 9. 19. Compounds according to the preceding claim com- laid sugar structure 9 D-glucose 1 OH Yy ° ÿrr HO '' γ 'ΌΗ OH EPO FORM 1503 12.99 (P04C14)