Classifications

• • C—CHEMISTRY; METALLURGY
  • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
  • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
  • C11D1/00—Detergent compositions based essentially on surface-active compounds; Use of these compounds as a detergent
  • C11D1/38—Cationic compounds
  • C11D1/52—Carboxylic amides, alkylolamides or imides or their condensation products with alkylene oxides
  • C11D1/528—Carboxylic amides (R1-CO-NR2R3), where at least one of the chains R1, R2 or R3 is interrupted by a functional group, e.g. a -NH-, -NR-, -CO-, or -CON- group
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/60—Sugars; Derivatives thereof
  • A61K8/602—Glycosides, e.g. rutin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
  • C07H15/02—Acyclic radicals, not substituted by cyclic structures
  • C07H15/12—Acyclic radicals, not substituted by cyclic structures attached to a nitrogen atom of the saccharide radical
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/74—Biological properties of particular ingredients
  • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
  • A61K2800/782—Enzyme inhibitors; Enzyme antagonists
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
  • Y02P20/00—Technologies relating to chemical industry
  • Y02P20/50—Improvements relating to the production of bulk chemicals
  • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

• the present invention relates to new compounds of the substituted 2-acylamino-2-deoxy-glucono-1,5,5-lactone type, compositions comprising such compounds, surfactants and / or biologically active, processes for obtaining these compounds as well as intermediate compounds for obtaining them.
• glycosylated surfactants comprising a lactone function
• Pocalyko et al. (1996) (5) and Kwoh et al. (1995) (3) describe the enzymatic synthesis of 6-O-dodecyl gluconolactone, while Kida et al. (1994) (1) pass through the lactone function in order to synthesize surfactants degradable into
• lactones do not contain an N-acyl or N-acetyl-glucosamine motif; this motif is important for the recognition of certain enzymes.
• A represents R ⁇ or -C (O) R 1 where R represents an alkyl group comprising from 1 to 30 carbon atoms, linear or branched, saturated or unsaturated, which can be partially or totally substituted by -Hal where Hal signifies - Cl, -Br-I or -F, and can be interrupted by one or more motifs chosen from -O-, -S-, -C (O) -, -NR 3 C (O) -, -Ph (R 4 ) n - and - (CH 2 -CH 2 -O) n .-
• R 3 represents -H or - (CH 2 ) n ..- CH 3 where n" is from 0 to 17, R 4 represents -H, -CH 3 , -C 2 H 5 , -C 3 H 7 and n is from 0 to 4 and n 'is 1, 2 or 3, or R, represents a cyclanic radical with diterpene or triterpene root, and R 2 represents a linear or branched C 1 to C 1 alkyl group
• the compounds of the invention have in particular the advantages of glycosylated surfactants based on glucosamine such as biodegradability. In addition, some of these compounds may have antimicrobial and antifungal properties. Finally, these compounds can be useful in processes of enzymatic inhibition or recognition of enzymes.
• the invention also relates to the processes for preparing the compounds of formula I above.
• These methods include at least the following steps: a) acylation of the glucosamine hydrochloride with the acid chloride of formula R 2 C (O) CI; b) protection of the hydroxyl in C1 by a group P 1 f in C3 and C4 by groups P 2 , and of the hydroxyl in C6; c) deprotection of the protected C6 hydroxyl; d) 6-O-acylation with a compound of formula R 1 C (0) CI or 6-O-alkylation with a compound of formula R., Hal to obtain the compound of formula
• compositions comprising at least one or more compounds of the invention, one or more several compounds obtained by the processes of the invention or intermediates in these processes.
• the invention relates to the compounds of formula I as surfactants or compounds useful in an enzymatic inhibition or enzyme recognition process.
• FIG. 1 represents the variation of the surface tension of water as a function of the logarithm of the concentration (in mol / 1) of the compound of the invention of formula I where A is C (O) C 7 H 15 and R 2 is CH 3 .
• FIG. 2 illustrates the inhibitory effect of 2-acetamido-2-deoxy-6-O-octanoyl-glucono-1, 5-lactone of formula I where A is C (O) C 7 H 15 and R 2 is CH 3 on bovine N-acetyl giucosaminidase.
• FIG. 3 represents the Dixon diagram confirming the competitive inhibition of N-acetyl glycosaminidase by the compound of the invention of formula I where A is C (O) C 7 H 15 and R 2 is CH 3 .
• FIG. 4 illustrates the inhibitory effect of the compound where A is C (O) C 7 H 15 and R 2 is CH 3 on the chitinases of Serratia marcescens.
• A represents -C (O) R 1 where R 1 represents a group comprising from 1 to 21 carbon atoms, preferably a linear C 5 to C 21 alkyl group, are preferred.
• R 2 represents an alkyl group nC p H 2p + 1 where p is from 1 to 7 are also preferred.
• One of the preferred compounds of the invention is that for which A is -C (O) -nC 7 H 15 and R 2 is CH 3 .
• lactone structure of this molecule gives it interesting biological properties such as the specific recognition of N-acetyl glucosaminidases (example 3).
• Kj inhibition constant of the order of 3 ⁇ M makes it suitable in the context of separation by affinity.
• the balance of lactone (closed form) and gluconic acid (open form) can allow efficient dissociation of the ligand / enzyme complex via a change in pH, for example.
• it is the preparation of a family of glycosylated surfactants from an N-acyl glucosamine.
• N-acyl glucosamine are generally obtained from glucosamine hydrochloride -product of the acid hydrolysis of chitin and an acid chloride.
• the starting material is N-acetyl glucosamine (NAG).
• the groups P and P 2 above are suitable conventional protecting groups for the hydroxyl groups of the carbohydrates.
• the allyl protective group for P 1 and the benzyl protective group for P 2 without that other suitable protection groups be excluded.
• protection at C6 can be carried out with a trityl group (Tr), without excluding other suitable protective groups; deprotection of the hydroxyl protected by Tr at C6 is carried out in an acid medium, in this particular embodiment.
• Tr trityl group
• the desallylation is carried out under mild conditions; finally, deprotection of the hydroxyls at C3 and C4 is done, in a particular embodiment, by catalytic hydrogenation.
• Hal represents Cl, Br, I or F, chlorine and bromine being preferred in the embodiment described below.
• the synthesis process consists of:
• the structure and purity of the products obtained can be determined by mass spectrometry, by 1 H and 1 C NMR, and by elementary analysis, as will appear in the examples.
• the surfactant properties of this particular example were determined by measuring the surface tension of solutions of different concentrations.
• the critical micelle concentration (CMC) was thus evaluated.
• the enzymes tested are for example bovine N-acetyl giucosaminidase, the chitinases of S. marcescens having chitobiase activity and lysozyme.
• compositions comprising the compounds of the invention.
• the above compounds can be used because of the following properties and / or in the following applications:
• enzymes in particular enzymes carrying out reactions involving N-acetylglucosamine, such as chitinases and N-acetyl glucosaminidases.
• compositions comprising at least one or more compounds of the invention, one or more compounds obtained by the process of the invention or one or more intermediate compounds.
• These compositions can be provided in particular for cosmetic or pharmaceutical use and then comprise an acceptable support for these applications. They can also be envisaged for a pesticidal, antibacterial, antifungal, insecticidal or antiviral application, and then comprise an acceptable support for these applications.
• compositions of the invention can also be detergent compositions, for example intended for the industrial environment.
• the detergent compositions according to the invention are characterized in that they contain from 0.1 to 60% by weight of one or more compounds of the invention, as well as 40 to 99.9% of a support acceptable for this application, for example a detergent base.
• the detergent base is usually chosen from anionic, nonionic, cationic or amphoteric surfactants and mixtures of these compounds.
• the adjuvant is usually chosen from the adjuvants or mixtures of adjuvants known in the field of detergents.
• compositions according to the invention are characterized in that they contain from 0.1 to 50%, preferably 5 to 35%, by weight of one or more compounds of the invention and an excipient and / or a base detergent and / or an adjuvant.
• the cosmetic compositions can be in the form of mild liquid soap, shampoo, bubble bath, shower gel or care formula, in particular ointment, cream and milk, aqueous or hydroalcoholic solution.
• composition of the invention when the composition of the invention is a mild liquid soap, it may contain from 5 to 35% by weight of a compound of the invention and from 70 to 95% by weight of an excipient.
• excipients, detergent bases and adjuvants are generally chosen from the compounds known to those skilled in the art. Mention may in particular be made of the compounds described in patent application EP 769499.
• compositions of this type When used for the treatment of the skin or hair, they can be in the form of cream, milk, emulsion (water in oil or oil in water), gel, solution aqueous or hydroalcoholic. They then contain, in addition, adjuvants such as perfumes, colorants, preservatives, thickening agents and emulsifying agents, any other common product known in the state of the art and commonly used to formulate compositions of this type.
• adjuvants such as perfumes, colorants, preservatives, thickening agents and emulsifying agents, any other common product known in the state of the art and commonly used to formulate compositions of this type.
• compositions intended for cleaning the hair may be in the form of an aqueous or hydroalcoholic solution, emulsion, cream, milk, gel and optionally be packaged in the form of an aerosol with a propellant.
• compositions When the compositions are intended for pharmaceutical use, they comprise a pharmaceutically acceptable carrier and can be in the form of an aqueous, hydroalcoholic solution, gel, cream, syrup or aerosol and contain usual adjuvants and pharmaceutically acceptable for the intended application.
• Formulations in which the compounds of the invention are in the form of reverse micelles may be useful, for their application to the liquid-liquid extraction of N-acetyl glycosaminidase in particular.
• apolar solvent such as isoctane for example, and comprising from 50 to 250 mM of AOT (sodium dioctyle sulfosuccinate), from 1 to 2.5 mM of one or more compounds of l invention, and from 0.5 to 6 M of water, optionally added with salt, and optionally comprising for example a buffer (90% KCI 0.1 M / 10% phosphate buffer 0.01 M pH 7), and optionally one or more co-solvents and / or co-surfactants.
• a buffer 90% KCI 0.1 M / 10% phosphate buffer 0.01 M pH 7
• co-solvents and / or co-surfactants for certain applications, it is possible to prepare unilamellar liposomes comprising, for example, in aqueous medium, phospholipids and one or more compounds of the invention.
• compositions of the invention can be used for the biological properties of the compounds of the invention, in particular in enzymatic inhibition or enzyme recognition processes.
• the examples below include such compositions.
• they comprise, in addition to one or more compounds of the invention, water, an aqueous buffer, for example an acetate buffer pH 4.5 (0.2 M) or phosphate buffer pH 6.6 (0.2 M); a hydroalcoholic support comprising one or more alcohols and adjuvants usual and suitable for the given application.
• compositions can also be in the form of emulsions or pre-emulsions, comprising for example the usual emulsifiers, adjuvants and thickeners and suitable for the intended application, or also in the form of a gel.
• the enzyme studied is hens lysozyme (Sigma, L-6876) at 0.5 g / 1 in 100 mM phosphate buffer pH 6.5 and the substrate consists of walls of Micrococcus lysodeikticus (Sigma) at 17 mg / 100 ml suspended in the same buffer.
• Protocol 100 ⁇ l of enzyme solution are diluted with 400 ⁇ l of the inhibitor solution. The whole is left at room temperature for 5 or 10 minutes. Then, 40 ⁇ l of the mixture are added to 3 ml of the substrate suspension in a spectrophotometer tank. The optical density is read at 450 nm every 10 seconds for 3 minutes.
• I50 is defined as the concentration of compound capable of inhibiting 50% of the enzymatic activity under the conditions of the assay.
• Example 1 Chemical synthesis of 2-acetamido-2-deoxy-6-O-octanoyl-glucono-1, 5-lactone from N-acetyl glucosamine (NAG).
• Step 1 consists in the preparation of allyl 2-acetamido-2-deoxy-glucopyranoside (b) from NAG:
• Step 2 consists in the preparation of allyl 2-acetamido-2-deoxy-
• Step 3 consists in the preparation of allyl 2-acetamido-2-deoxy-6-O-trityl-3,4-O-dibenzyl-glucopyranoside (d):
• Step 4 consists in the preparation of allyl 2-acetamido-2-deoxy-3,4-O-dibenzyl-glucopyranoside (e):
• Step 5 consists in the preparation of allyl 2-acetamido-2-deoxy-
• Step 6 consists in the preparation of 2-acetamido-2-deoxy-6-O-octanoyl-3,4-O-dibenzyl-glucopyranose (g):
• Step 7 consists in the preparation of 2-acetamido-2-deoxy-6-O-octanoyl-3,4-O-dibenzyl-glucono-1, 5-lactone (h):
• Step 8 consists in the preparation of 2-acetamido-2-deoxy-6-O-octanoyl-glucono-1, 5-lactone (i): 160 mg of (h) were dissolved in 10 ml of methanol containing
• Example 2 Surfactant properties. Determination of the critical micelle concentration (CMC).
• the CMC of 2-acetamido-2-deoxy-6-O-octanoyl glucono-1, 5-lactone is equal to 25 mM, and is of the same order of magnitude as those of HECAMEG (22 mM) and octyl glucoside (18 mM).
• Example 3 Biological properties: enzymatic inhibitions.
• the inhibition of N-acetyl giucosaminidase by (i) is therefore demonstrated.
• the I50 of (i) is around 7 ⁇ M.
• the I50 in this case is of the order of 1.2 mM.

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• 1998
  • 1998-11-19 FR FR9814564A patent/FR2786187B1/fr not_active Expired - Fee Related
• 1999
  • 1999-11-19 EP EP99956103A patent/EP1131311A1/fr not_active Withdrawn
  • 1999-11-19 WO PCT/FR1999/002861 patent/WO2000031059A1/fr not_active Application Discontinuation
  • 1999-11-19 AU AU12781/00A patent/AU1278100A/en not_active Abandoned
  • 1999-11-19 CA CA002351664A patent/CA2351664A1/fr not_active Abandoned
  • 1999-11-19 JP JP2000583887A patent/JP2002530395A/ja active Pending
• 2001
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