NEW MOLECULES DERIVED FROM FURANACRYLATES AND 5-HYDROXYMETHYL FURANACRYLATES WITH UV-B FILTER AND / OR ANTIMICROBIAL PROPERTIES

Abstract

The invention relates to the field of anti-UV and antimicrobial agents. More particularly, the invention relates to the use of furanacrylate and 5-hydroxymethyl furanacrylate derivatives as anti-UV-B and antimicrobial agents. These compounds can also be used as dyes or surfactants. The invention also relates to novel compounds derived from furanacrylates and 5-hydroxymethyl furanacrylates.

Description

Title of the invention: NEW MOLECULES DERIVED FROM FURANACRYLATES AND 5-HYDROXYMETHYL FURANACRYLATES WITH UV-B FILTER AND / OR ANTIMICROBIAL PROPERTIES

[0001] The invention relates to the field of anti-UV and / or anti-microbial agents. More particularly, the invention relates to the use of furanacrylate and 5-hydroxymethyl furanacrylate derivatives as anti-UV-B and / or anti-microbial agents. These compounds can also be used as dyes or surfactants. The invention also relates to novel compounds derived from furanacrylates and 5-hydroxymethyl furanacrylates. Field of invention

[0002] Sunscreens are made up of molecules capable of absorbing UV rays. Among the most effective and widely used UVB filters in sunscreens is octinoxate. However, this molecule is considered an endocrine disruptor and its use is controversial due to public health risks.

[0003] Research is being conducted to propose molecules for use as sunscreens and / or antimicrobial agents with low environmental and health impact. However, most of the bio-sourced molecules developed to date are not stable enough and / or not very effective.

[0004]

[0005] There is a need to have molecules that are non-toxic to the skin and the environment to replace the reference molecules used to date. Description of the invention

[0006] The inventors have developed a new family of aromatic compounds from wood: furans and have demonstrated their anti-UV-B and antimicrobial properties.

[0007] Thus, the invention relates to the use of a compound of formula (I)

[0008] [Chem.l] : To j : ' xZ ; zV'Ay! : h To ÿ o; : rZ^ ; ; r s (i)

[0009] as an anti-UV-B and / or antimicrobial agent.

[0010] The invention also relates to novel furanacrylate and 5-hydroxymethylfuranacrylate derivatives corresponding to formula (I). Advantages of the invention

[0011] The compounds of formula (I) exhibit both anti-UV-B and antimicrobial properties, which allows them to be used for one or the other of these properties, but also to benefit from these two properties at the same time.

[0012] The compounds of formula (I) can also be used as a colorant, in a range from yellow to orange and pink and / or as surfactants.

[0013] The compounds according to the invention are biosourced compounds synthesized from lignocellulosic biomass (for example wood), which makes it possible to meet the expectations of cosmetics players, in search of effective ingredients which are ecological and eco-responsible, in particular biosourced and less impactful for the environment, whether in terms of sourcing or process.

[0014] Sourcing these compounds from wood co-products is generally advantageous in all the fields of application envisaged: agri-food, phytosanitary products, and additives for polymers, in particular bio-sourced polymers, in addition to cosmetics. DETAILED DESCRIPTION OF THE INVENTION

[0015] A first object of the invention relates to the use of a compound of formula (I)

[0016] [Chem.l] ■ AR: ! ! GH ' xi-FL rZ : " : 0 / —* : bZ”1 ; : ' Rg: (i)

[0017] in which:

[0018] X is a linear, cyclic or branched alkane or alkene or alkyne ranging from C1 to C30 or O or S or NH or NR6 Ri is an alkoxide, alkane or alkene or alkyne ranging from Ci to C30 linear, cyclic or branched, or OH

[0020] R2 is an H group or an alkane or alkene or alkyne ranging from C1 to C30, linear, cyclic, aromatic or branched, or an isosorbide group,

[0021] or a group (CH2)nN(R7)3+ or (CH)(COO)(CH2)nN(R7)3+ with n an integer between 0 and 5,

[0022] or a group CH(COOH)CH3 or CH(COOH)(CH2)n(COOH) or CH(COOH) (CH2)n(CH)(CHOH)COOH with n being an integer between 0 and 5,

[0023] or a linear, cyclic or branched, saturated or unsaturated (CH2)XOH or (CH2)XNH2 or (CH2)XCOOH group, with x between 1 and 30, linear, cyclic or branched, or a R8-A group

[0024] R3 is a H, OH, NH2 group, a cyano group or a halogen (CH2)nOH, (CH2)nOCOR7 or (CH2)nOR7, with n being an integer between 0 and 5

[0025] or a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group

[0026] or an amine of the NHR, NR2 or NRR' type, with R and R' independently chosen from a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group

[0027] or an ester carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a benzoyl group

[0028] or an amide carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group

[0029] or a ketone carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group

[0030] or an ether carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a silyl or benzyl or benzoyl group

[0031] R4 and R5 are a H or OH or NH2 group or a cyano group or a halogen or a (CH2)XOH or (CH2)XNH2 or (CH2)XCO(CH2)X CH3 group, or (CH2)xCOOH in linear, cyclic or branched, saturated or unsaturated form, with x and x' an integer independently chosen from an alkane or alkene or alkyne group ranging from 1 to 30 linear, cyclic or branched form

[0032] or a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group

[0033] or an amine of the NHR, NR2 or NRR' type, with R and R' independently chosen from a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group

[0034] or an ester carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a benzoyl group

[0035] or an amide carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group

[0036] or a ketone carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group

[0037] or an ether carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a silyl or benzyl or benzoyl group;

[0038]

[0039]

[0040]

[0041]

[0042]

[0043]

[0044]

[0045]

[0046]

[0047]

[0048]

[0049] with R4 and R5 being able to combine to form a ring of type -(CH2)n- or -(CH)n- with n an integer between 4 and 8. R6 is a linear, cyclic or branched, saturated or unsaturated C1-C30 alkyl group R7 is independently selected from a linear, cyclic or branched C1 to C30 alkane or alkene or alkyne R8 is a linear, cyclic or branched, saturated or unsaturated C1-C30 alkyl group or a CH(COOH)(CH2)n(CH)COOH group with n an integer between 0 and 5 or a group (CH2)X(CHOH)(CH2)X with x and x' an independently chosen integer ranging from 0 to 5 as an anti-UV-B and / or antimicrobial agent. In a first preferred embodiment of the invention, the compounds of formula (I) are furanacrylate derivatives chosen from the following compounds 1 to 10: [Chem. 2] [Chem. 4]

[0050] [Chem.6]

[0051] [Chem.7]

[0052] [Chem. 8]

[0053] [Chem.9]

[0054] [Chem. 10] O * S:

[0055] [Chem. 11]

[0056] In a second preferred embodiment of the invention, the compounds of formula (I) are 5-hydroxymethylfuranacrylate derivatives chosen from the following compounds 11 to 21:

[0057] [Chem. 12] O A OH Aô .À... A y Q OH VJ J OH

[0058] [Chem. 13] QM

[0059] OH [Chem. 14]

[0060] [Chem. 15] OH

[0061] [Chem. 16] OH

[0062] [Chem. 17] OH

[0063] [Chem. 18] OH

[0064] [Chem. 19] O

[0065] OH [Chem. 20] OH

[0066] [Chem.21]

[0067] [Chem.22] HO \

[0068] In the application as an anti-UV-B agent, particularly interesting compounds are compounds 6, 7, 16, 17 and 21.

[0069] Generally speaking, compounds based on furanacrylate appear to be more active on the microorganisms tested than compounds based on 5-hydroxymethylfuranacrylate. In the application as an antimicrobial agent, particularly interesting compounds are compounds carrying at least one acid function as well as one ester function (compounds 1, 4, 6).

[0070] The compounds of formula (I) have coloring powers ranging from yellow to pink. Thus, they can also be used as coloring agents.

[0071] The compounds according to the invention can be used as surfactants, particularly compounds 8 and 19.

[0072] The compounds according to the invention can be used as platform molecules and as finished chemical products.

[0073] They find their application in different fields such as: - Food industry: for food protection, as a preservative, in packaging - Cosmetology: as UV-B filters, preservatives, ingredients, surfactants, colorants or pigments - Phytosanitary: as an adjuvant, UV protection of phytosanitary products - Additives for polymers - as additive, monomer, crosslinking agent and colorant

[0074] A second subject of the invention relates to new compounds derived from furanacrylates and 5-hydroxymethyl furanacrylates.

[0075] Indeed, the inventors identified compounds 3, 4, 6, 9, 10, 12, 13, 15, 18, 19, 20 and 21 which had never been described before. These compounds all carry very interesting anti-UV-B and / or antimicrobial activity. DESCRIPTION OF FIGURES

[0076] [Fig.l] [Fig.l]: Absorbance spectrum of compounds 4, 5 and 8 of the furanacrylate series

[0077] [Fig.2] [Fig.2]: Absorbance spectra of compounds 17, 18 and 21 of the 5- series hydroxymethyl furanacrylates EXAMPLES

[0078] EXAMPLE 1: Process for the synthesis of new furanacrylate and 5-hydroxymethyl furanacrylate derivatives

[0079] The compounds of formula (I) were prepared using the following synthetic routes:

[0080] [Chem.23] r2oh THF. 75 nC 4 p.m. O^O ACN, 60 X, 4 h r2nh2 or HZO, reflux. 1h \ If v x-Rj Proline D EtOH, 60°C r5 4 hours

[0081] The products were purified on a chromatography column.

[0082] EXAMPLE 2: Anti-UV-B properties of furanacrylate and 5-hydroxymethylfuranacrylate derivatives

[0083] 1 - Absorbance of furanacrylate derivatives

[0084] The processes described in Example 1 made it possible to obtain both monomers (compounds 1 to 8) and dimers (compounds 9 and 10).

[0085] The absorbance of these molecules was evaluated and the results are shown in [Fig.l]. They absorb mainly in the UV-B zone with a coverage area extremely close to that of octinoxate which is the reference UV-B filter currently used on the market.

[0086] Several molecules have spectra that match perfectly in terms of coverage area with octinoxate (compounds 4, 6), others are slightly shifted. The use of dimers makes it possible to obtain a coverage area that matches perfectly with that of octinoxate but with an absorbance almost 2 times higher (compound 10). This makes them excellent candidates for substituting octinoxate.

[0087] 2- Absorbance of 5-hydroxymethylfuranacrylate derivatives

[0088] The processes described in Example 1 made it possible to obtain both monomers (compounds 11 to 19) and dimers (compounds 20 and 21).

[0089] The absorbance of these molecules was evaluated and the results are shown in [Fig.2]. They absorb mainly in the UV-B zone with a coverage area close to that of octinoxate which is the reference UV-B filter currently used on the market.

[0090] All molecules exhibit spectra close to octinoxate in terms of coverage area (compounds 17, 18). The use of dimers makes it possible to obtain an absorbance significantly higher than that of octinoxate (compound 21). These results highlight very good candidates for substituting this molecule.

[0091] EXAMPLE 3: Anti-UV-B properties of furanacrylate and 5-hydroxymethylfuranacrylate derivatives

[0092] The absorbance capacity and stability over time of the compounds during UV exposure for 1 h. The results are grouped in the following Table 1:

[0093] [Tables 1] Molecules Absorbance (t=0 min) Loss of absorbance (%) Octinoxate (reference) 0.23925 25.3 1 0.21797 6.5 2 0.23233 22.5 3 0.24705 6.1 4 0.255262 9.6 5 0.25777 10.5 6 0.261853 1.3 7 0.33275 5.8 8 0.411389 22.4 9 0.465565 5.7 10 0.17853 10.3 11 0.19027 18.1 12 0.20779 8.2 13 0.236554 13.4 14 0.24019 10.9 15 0.24792 4.7 16 0.26290 0.7 17 0.28388 2.6 18 0.31577 22.7 19 0.18844 3.1 20 0.416504 6.7 21 0.498507 0.7

[0094] Table 1: Anti-UV properties of compounds 1 to 21

[0095] The stability of compounds varies, regardless of the series to which they belong. However, all compounds stand out with an absorbance loss lower than the 25% of octinoxate. Compounds 6, 16, and 21 exhibit extremely low absorbance loss percentages, which are truly very interesting. However, the other compounds remain very competitive.

[0096] EXAMPLE 4: Antimicrobial properties of furanacrylate and 5-hydroxymethylfuranacrylate derivatives

[0097] Antimicrobial tests were then carried out to determine the ability of the synthesized compounds to inhibit the growth of E. Coli, Candida albicans and Bacillus subtilis strains. The inhibitory concentrations vary from 2.5% to 0.01% w / v. The evaluation of other strains is also planned, in particular: Staphylococcus Aureus, Pseudomonas aeruginosa, Aspergillus brasiliensis. These strains correspond in particular to the strains classically screened for cosmetic preservatives. The minimum inhibitory concentrations (MIC) are expressed as a percentage (w / v) and grouped in the following Table 2.

[0098] [Tables2] Molecules E. Coli c. Albicans B. Subtilis P. Aeruginosa S. Aureus A. Brasiliensis Ethyl Paraben (reference) 1.25% 1.25% 1.25% * * * 1 1.25% 0.625% - * * * 2 - - - * * * 3 - - 0.31% * * * 4 1.25% 0.625% 2.5% * * * 5 1.25% - 1.25% * * * 6 0.42% 0.83% 0.11% * * * 7 - - - * * * 8 - - - * * * 9 - - 1.25 * * * 10 - - 1.25% 11 2.5% - 1.25% * * * 12 0.31% - 0.31% * * * 13 - - - * * * 14 1.25% - - * * * 15 1.25% - 1.25% * * * 16 - - - * * * 17 - - 0.31% * * * 18 0.625% 0.31% 0.625% * * * 19 - - - 20 - - - * * * 21 - - - * * *

[0099] Table 2: Minimal inhibitory concentrations of compounds 1 to 21 compared to that of ethyl paraben (reference molecule) (* data currently being acquired)

[0100] EXAMPLE 5: Coloring properties of furanacrylate and 5-hydroxymethylfuranacrylate derivatives

[0101] Some molecules have interesting colors (yellow, orange, red, pink). They can be used as pigment / colorant for various applications, particularly cosmetics.

[0102] EXAMPLE 6: Surfactant properties of 5-hydroxymethylfuranacrylate derivatives

[0103] Certain molecules, such as derivatives of molecule 19, have interesting foaming properties. They can be used as surfactants for various applications, particularly cosmetics.

Claims

Claims

1. Compound of formula (I) [Chem.l] (I) in which: X is an alkane or alkene or alkyne ranging from C1 to C30 linear, cyclic or branched or O or S or NH or NR6 Ri is an OH R2 is an H group or a linear, cyclic, aromatic or branched alkane or alkene or alkyne ranging from C1 to C30, or an isosorbide group, or a (CH2)nN(R7)3+ or (CH)(COO)(CH2)nN(R7)3+ group with n an integer between 0 and 5, or a CH(COOH)CH3 or CH(COOH)(CH2)n(COOH) or CH(COOH)(CH2)n(CH)(CHOH)COOH group with n being an integer between 0 and 5, or a linear, cyclic or branched, saturated or unsaturated (CH2)XOH or (CH2)XNH2 or (CH2)XCOOH group, with x between 1 and 30, linear, cyclic or branched, or an R8-A group R3 is a H, OH, NH2 group, a cyano group or a halogen (CH2)nOH, (CH2)nOCOR7 or (CH2)nOR7, with n being an integer between 0 and 5 or a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an amine of type NHR, NR2 or NRR', with R and R' independently chosen from a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an ester bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a benzoyl group or an amide bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or a ketone bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an ether bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a silyl or benzyl or benzoyl group R4 and R5 are a H or OH or NH2 group or a cyano group or a halogen or a (CH2)XOH or (CH2)XNH 2 or (CH2)xCO(CH2)x CH3 group, or (CH2)xCOOH in linear, cyclic or branched, saturated or unsaturated form, with x and x' an integer independently chosen from an alkane or alkene or alkyne group ranging from 1 to 30 linear, cyclic or branched form or a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an amine of type NHR, NR2 or NRR', with R and R' independently chosen from a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an ester bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a benzoyl group or an amide bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or a ketone bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an ether carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a silyl or benzyl or benzoyl group; with R4 and R5 being able to combine to form a ring of the type -(CH2)n- or -(CH)n- with n an integer between 4 and 8. R6 is a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group R7 is independently selected from a linear, cyclic or branched C1 to C30 alkane or alkene or alkyne R8 is a linear, cyclic or branched, saturated or unsaturated C1-C30 alkyl group or a CH(COOH)(CH2)n(CH)COOH group with n an integer between 0 and 5 or a group (CH2)X(CHOH)(CH2)X' with x and x' an independently chosen integer ranging from 0 to 5

2. for its use as an anti-UV-B agent Compound of formula (I): [Chem.l] (I) in which: X is an alkane or alkene or alkyne ranging from C1 to C30 linear, cyclic or branched or O or S or NH or NR6 Ri is an OH R2 is an H group or an alkane or alkene or alkyne ranging from C1 to C3o linear, cyclic, aromatic or branched, or an isosorbide group, or a group (CH2)nN(R7)3+ or (CH)(COO)(CH2)nN(R7)3+ with n an integer between 0 and 5, or a CH(COOH)CH3 or CH(COOH)(CH2)n(COOH) group or CH(COOH)(CH2)n(CH)(CHOH)COOH with n being an integer between 0 and 5, or a linear, cyclic or branched, saturated or unsaturated (CH2)XOH or (CH2)XNH2 or (CH2)XCOOH group, with x between 1 and 30, linear, cyclic or branched, or a R8-A group R3 is a H, OH, NH2 group, a cyano group or a halogen (CH2)nOH, (CH2)nOCOR7 or (CH2)nOR7, with n being an integer between 0 and 5 or a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an amine of type NHR, NR2 or NRR', with R and R' independently chosen from a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an ester bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a benzoyl group or an amide bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or a ketone bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an ether bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a silyl or benzyl or benzoyl group R4 and R5 are a H or OH or NH2 group or a cyano group or a halogen or a (CH2)XOH or (CH2)XNH 2 or (CH2)xCO(CH2)x CH3 group, or (CH2)xCOOH in linear, cyclic or branched, saturated or unsaturated form, with x and x' an integer independently chosen from an alkane or alkene or alkyne group ranging from 1 to 30 linear, cyclic or branched form or a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an amine of type NHR, NR2 or NRR', with R and R' independently chosen from a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an ester bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a benzoyl group or an amide bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or a ketone bearing a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group or an ether carrying a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group, or a silyl or benzyl or benzoyl group; with R4 and R5 being able to combine to form a ring of the type -(CH2)n- or -(CH)n- with n an integer between 4 and 8. R6 is a linear, cyclic or branched, saturated or unsaturated C1 to C30 alkyl group R7 is independently selected from a linear, cyclic or branched C1 to C30 alkane or alkene or alkyne R8 is a linear, cyclic or branched, saturated or unsaturated C1-C30 alkyl group or a CH(COOH)(CH2)n(CH)COOH group with n an integer between 0 and 5 or a group (CH2)X(CHOH)(CH2)X' with x and x' an independently chosen integer ranging from 0 to 5 for its use as an anti-UV B agent in cosmetics.

3. Compound according to one of claims 1 or 2 for its use according to one of claims 1 or 2 in which said compounds of formula (I) are furfuranacrylate derivatives chosen from the following compounds 1 to 10: [Chem.2] GTÎ O' oh A [Chem. 3] ' X) AA© OH W [Chem.4] 0 / AN Vo A HA O OH A [Chem. 5] O 1 / AA 0 ' X * J "O q-ZCqh A [Chem.6] o / A^t'OH Ao AAO^OH [Chem.9] [Chem. 10] [Chem. 11]

4. Compound according to one of claims 1 or 2 for its use according to one of claims 1 or 2 in which said compounds of formula (I) are 5-hydroxymethylfurfuranacrylate derivatives chosen from the following compounds 11 to 21: [Chem. 12] O OH Chem. 13] VA' A° c oh Chem. 14] 'T V-Ô / c OH Chem. 15] * ^-'0 .. 0 OH Chem. 16] Vô ....-:■ / 0' < ^OH Chem. 19] OA r cr o OH g JH ,--, )^0H 0 -, A .. xy H' A H., ix OH ' 0 ^OH 0 i .-JC y "o ' xx%oh VA H (18 [Chem.20] O ^-Ô 0^0H ^9; ? 'Oh [Chem.21] HO [Chem.22] HO

5.

6.

7.

8. OH Compound according to one of claims 3 or 4 for its use according to one of claims 3 or 4 in which said anti-UV-B compounds are chosen from compounds 6 and 21. Compound according to one of claims 3 or 4 for its use according to one of claims 3 or 4 in which said compounds are furthermore to be used as surfactants and are chosen from compounds 8 and 19. Compound according to one of claims 1 to 3 for its use according to one of claims 1 or 3 in which said compounds are further used as a coloring agent. Compound of formula (I) exhibiting anti-UV-B activity chosen from the following compounds: [Chem.4] O [Chem.5] [Chem. 10] G-'v < Xs. [Chem. 11] Fabric. 13] >- or OH Chem. 14] P 'T or OH Chem. 16] V-to / 0 XQH Chem. 19] for OH Chem.20] Z''^ / 0 / OH / '"“X .... X .... < '®> X / X\ ÇM\ / .... X x—x ( '■■-zy \ / / X ZI x ZI y -- X__ / / P 0=4 OPxX / P o r 'o x / . 'o / / n= / In X / [Chem.21]

Images