WO2004044216A1 - Proprietes antimicrobiennes de diverses formes de sophorolipides - Google Patents

Proprietes antimicrobiennes de diverses formes de sophorolipides Download PDF

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WO2004044216A1
WO2004044216A1 PCT/US2003/035871 US0335871W WO2004044216A1 WO 2004044216 A1 WO2004044216 A1 WO 2004044216A1 US 0335871 W US0335871 W US 0335871W WO 2004044216 A1 WO2004044216 A1 WO 2004044216A1
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glucopyranosyl
oxy
cis
octadecenoate
sophorolipid
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PCT/US2003/035871
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English (en)
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Richard A. Gross
Vishal Shah
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Polytechnic University
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Priority to AU2003299557A priority Critical patent/AU2003299557A1/en
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Priority to US11/020,683 priority patent/US20050164955A1/en

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    • 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
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/48—Medical, disinfecting agents, disinfecting, antibacterial, germicidal or antimicrobial compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/18—Liquid substances or solutions comprising solids or dissolved gases
    • 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
    • C11D1/02—Anionic compounds
    • C11D1/04—Carboxylic acids or salts thereof
    • C11D1/06—Ether- or thioether carboxylic acids
    • 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
    • C11D1/66—Non-ionic compounds
    • C11D1/667—Neutral esters, e.g. sorbitan esters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/44—Preparation of O-glycosides, e.g. glucosides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/44—Preparation of O-glycosides, e.g. glucosides
    • C12P19/60—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin
    • C12P19/62—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin the hetero ring having eight or more ring members and only oxygen as ring hetero atoms, e.g. erythromycin, spiramycin, nystatin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters

Definitions

  • the present invention in general relates to the field of uses for sophorolipids and more specifically to the field of uses of sophorolipids as antibacterial, anti-spermicidal and anti-viral agents.
  • sophorolipids occurs as a mixture of macrolactone and free acid structures that are acetylated to various extents at the primary hydroxyl position of the sophorose ring.
  • Careful examinations have revealed that at least eight structurally different sophorolipids are produced.
  • the main component of sophorolipids is 17- hydroxyoctadecanoic acid and its corresponding lactone. Tulloch, A.P. et al., Can. J.
  • glycolipids may be useful in treating very severe immune disorders.
  • glycolipids have been reported to be of interest for in vivo cancer treatment/antitumor cell activity, treatment of autoimmune disorders, in vivo and in vitro antiendotoxic (septic) shock activity, regulation of angiogenesis, and apoptosis induction, all by cytokine activity. See, e.g., US Patent No. 5597573 to Massey, US Patent No. 5514661 to Piljac, US Patent No. 5648343 to Carlson, and the references cited in notes 9-13 of Bisht, K.S. et al., J. Org. Chem, vol. 64, pp. 780-789 (1999).
  • Sophorolipids are microbial extracellular glycolipids produced by resting cells of Candida bombicola.
  • the chemical composition of sophorolipid is constituted by a disaccharide sugar viz. sophorose and a fatty acid or an ester group.
  • Candida bombicola produces the sophorolipids as a mixture of macroloctones and free acid structures that are acetylated to various extents at the primary hydroxyl sophorose ring positions (FIG. 1). Bisht, K.S. et al., J. Org. Chem., vol. 64, pp. 780-789 (1999).
  • a natural mixture of sophorolipids is synthesized by fermentation of Candida bombicola. Lactonic sophorolipid was separated from the natural mixture. Also, the natural mixture was treated to obtain open ring sophorolipid. Ethyl 17-L-[(2'-0- ⁇ -D-glucopyranosyl- ⁇ -D-glucopyranosyl)- oxy]-cis-9-octadecenoate then was synthesized and then further treated to obtain Ethyl 17-L[(2'-0- ⁇ -D glucopyranosyl- ⁇ -D-glucopyranosyl)-oxy]-cis-9- octadecenoate 6',6"-diacetate.
  • Ethyl 17-L-[(2 ' -0- ⁇ -D-glucopyranosyl- ⁇ -D- glucopyranosyl)-oxy]-cis-9-octadecenoate-6"-acetate also was synthesized by adding Lipase to a solution of ethyl ester, (325.4 mg) and vinyl acetate (230.9 ⁇ l) in dry THF (5 ml), and further treatment.
  • Hexyl 17-L-[(2'-0- ⁇ -D-glucopyranosyl- ⁇ - D-glucopyranosyl)-oxy]-cis-9-octadecenoate and Methyl 17-L-[(2'-0- ⁇ -D- glucopyranosyl- ⁇ -D-glucopyranosyl)-oxy]-cis-9-octadecenoate also were synthesized.
  • Various organisms were treated with the sophorolipids and the ability of the sophorolipids to inhibit growth of the organisms was measured. The ability of various forms of sophorolipids to inhibit the growth of organisms varies on the type of organism under test. In general, the sophorolipids are highly effective to smaller sized bacteria. All sophorolipids are selectively active against certain forms of organisms.
  • sophorolipids in field of medicine would be tremendous to treat various infections, apart from other applications. Further, while sophorolipids can find applications in diverse fields, the present invention indicates that sophorolipids can be used as anti-spermicidal, anti-viral and anti- bacterial agents.
  • FIG. 1 are representative structures of sophorolipids produced by Candida bombicola, with FIG. 1A showing lactonic sophorolipid and FIG. 1B showing open ring sophorolipid.
  • Sophorolipid Fermentation Sophorolipids were synthesized by fermentation of Candida bombicola.
  • the fermentation media was composed of 100 g glucose, 10 g yeast extract, 1 g urea and 40 g oleic acid in 1000 ml of water. After 7 days of fermentation, sophorolipid was extracted thrice using ethyl acetate. The extracts were pooled and the solvent then was removed. The obtained product then was washed with hexane to remove the residual fatty acids. This was "natural" sophorolipid. The sophorolipid was dried in a vacuum desiccator.
  • Ethyl 17-L-[(2'-0- ⁇ -D-glucopyranosyl- ⁇ -D-glucopyranosyl)-oxy]-cis-9- octadecenoate was synthesized by adding 2 g of dry crude sophorolipid and 2.5 mL 0.021 N sodium ethoxide in methanol solution to a 100 mL round-bottomed flask equipped with a reflux condensor. The reaction assembly was protected from atmospheric moisture by a CaCI 2 guard tube. The reaction mixture was refluxed for 3 hr, cooled to room temperature (30°C), and acidified using glacial acetic acid.
  • methyl- and butyl-based compounds can be accomplished by substituting sodium methoxide or sodium butoxide respectively for the sodium ethoxide, resulting in sophorolipid methylester and sophorolipid butylester, respectively.
  • the amount of dry crude sophorolipid and the amount and normality of the sodium (CH 2 ) n oxide can be , varied appropriately by those of ordinary skill in the art without undue experimentation.
  • methyl- and butyl-based compounds can be accomplished by substituting methyl ester or butyl ester respectively for the ethyl ester.
  • the amount of vinyl acetate, THF and Lipase can be varied appropriately by those of ordinary skill in the art without undue experimentation.
  • Other types of suitable sophorolipids also can be synthesized by those of ordinary skill in the art without undue experimentation.
  • Hexyl 17-L-[(2'-0- ⁇ -D-glucopyranosyl- ⁇ -D-glucopyranosyl)-oxy]-cis-9- octadecenoate was synthesized by adding 2 g of dry crude sophorolipid and 2.5 mL 0.021 N sodium hexanoxide in hexanol solution to a 100 mL round-bottomed flask equipped with a reflux condensor. The reaction assembly was protected from atmospheric moisture by a CaCI 2 guard tube. The reaction mixture was refluxed for 3 hr, cooled to room temperature (30°C), and acidified using glacial acetic acid.
  • reaction mixture was concentrated by rotoevaporation and poured with stirring into 100 mL of ice-cold water that resulted in the precipitation of the sophorolipid ethylester as a white solid.
  • the precipitate was filtered, washed with ice-water, and lyophilized.
  • sophorolipids also can be synthesized by those of ordinary skill in the art without undue experimentation.
  • Sophorolipid solution was prepared by adding 20 mg compound in 1 ml
  • sophorolipids As shown in Table 1 , the ability of an effective amount of various forms of sophorolipids to inhibit the growth of an organism varies on the type of organism under test.
  • the invention illustrates the use of natural, lactonic, open ring, ethyl ester, methyl ester, hexyl ester, 6'-acetate ethyl ester, 6',6"-diacetate ethyl ester sophorolipids as anti-bacterial agents.
  • reaction mixture was concentrated by rotoevaporation and poured with stirring into 100 mL of ice-cold water that resulted in the precipitation of the sophorolipid methylester as a white solid.
  • the precipitate was filtered, washed with ice water, and lyophilized, resulting in 8.77 g of product (yield 95.0%).
  • Novozyme 435 catalyzed synthesis of 17-L-([2'-0- ⁇ -D-glucopyranosyl- ⁇ -D- glucopyranosyl]-oxy)-cis-9-octadecenoic acid 1', 6"-lactone (sophorolactone, 9).
  • an inert atmosphere was maintained using a glovebag and dry argon.
  • a control reaction was set up as described above except Novozyme 435 was not added.
  • TLC CHCI 3 /MeOH, 7:3 was used to follow the progress of the reaction.
  • the reaction was quenched by removing the enzyme and zeolite by vacuum filtration (glass fritted filter, medium porosity), the enzyme was washed 3-4 times with 5 mL portions of THF, the filtrates were combined, and solvent was removed in vacuo to give 1.45 g of the product.
  • the crude product (1.45 g) was purified by column chromatography over silica gel (100 g, 130-270 mesh, 60 A, Aldrich) using a gradient solvent system of chloroform/methanol (2 mL/minute) with increasing order of polarity to give 1.2 g (yield 84%) of purified product.
  • the proton NMR spectrum of the compound showed a downfield shift in the resonance positions of both the C-6' and C-6" protons. However, conclusive determination of the position of the acryl groups in the molecule was not possible from the proton NMR spectrum due to its complexity.
  • the 13 C NMR spectrum of this product was edited using a DEPT 135 pulse sequence to separate out the resonances due to the metheine and methyl carbons from those due to the methylene carbons.
  • Methyl 17-L-([2'-0- ⁇ -D-glucopyranosyl- ⁇ -D-glucopyranosyl]-oxy)-cis-9- octadecenoate 6',6"-diacetate (5) was prepared by the Novozyme 435 catalyzed acylation of methyl 17-L-([2'-0- ⁇ -D-glucopyranosyl- ⁇ -D-glucopyranosyl]-oxy)-cis- 9-octa-decenoate (SL-Me, 1), using vinyl acetate in dry THF.
  • the DEPT 135 spectrum of 5 when compared to that of 1 , showed a downfield shift of about 2.0 ppm in the resonance position of C-6' and C-6" and an upfield shift of about 2.5 ppm in the resonance position of C-5' and C-5". Furthermore, except for the downfield shift of ⁇ 2 ppm in the resonance position of C-2', there were no observable changes in the resonance position of the other carbons in the molecule. Hence, it was concluded that the acetylation of 1 with vinyl acetate catalyzed by the lipase Novozyme 435 was highly regioselective.
  • Spectral data for 6 and 7 were similar to that observed for 5 with additional resonances that correspond to the ester alkyl group.
  • the DEPT 135 spectra of 6 and 7, when compared to that of 1 also showed a downfield shift of about 2.0 ppm in the resonance position of C-6' and C-6" and an upfield shift of about 2.5 ppm in the resonance position of C-5' and C-5".
  • One of the objectives of this invention is the site-selective synthesis of a monoacryl derivative of 1.
  • a monoacryl derivative of 1 Such a product could be used as a glycolipid monomer that is polymerizable to linear chains through well-established free radical methods.
  • reactions of 1 were conducted where the ratio of 1 to vinyl acrylate was varied. When the ratio of 1 to vinyl acrylate was 1 :1 or less, 9 ([ ⁇ ] 25 D -4.25, mlz 627.95 (M + Na) + ) was formed. Compound 9 was separated from the unreacted SL-Me by column chromatography.
  • the structure of the lactone 9 is very interesting, as it is an unnatural analogue of the microbially produced macrolactone.
  • the lactone 9 differs in the site at which the sophorose ring is attached to the fatty acid. Specifically, in 9, unlike the natural sophorolipids, the fatty acid carboxyl carbon (C-1 ) is linked to the C-6" hydroxyl, not to the C-4" hydroxyl.
  • a structure has been proposed based on the lactonic structure 9 for a diacetyl sophorolipid isolated from a strain of Torulopsis gropengiesseri. The structure was proposed to be a 1 ,6"-lactone having acetate groups at the hydroxyls of C-6 1 and C-3".
  • sophorolipid ethyl ester which was obtained by treating the microbial sophorolipid mixture with sodium ethoxide, was used as a synthon for enzyme- mediated transformations to form corresponding sophorolipid monoacetate, amide, and other monoacyl and diacyl derivatives.
  • the optically active 11 ([ ⁇ ] 25 D -10.80) was identified by an LC-APCI mass spectrum (m/z 715.51 [M+Na] + and 693.52 [M+H] + ), and detailed NMR spectral analyses.
  • the appearance in 1 H-NMR of additional resonances at 1.90-2.18 ppm (m) for three protons, and the downfield shift of two protons of ethyl ester at 3.20-3.95 ppm (m) to 4.21 (1 H, m) and 4.39 (1 H, m) for 11 showed the presence of one acetyl group in the molecule.
  • Lipase PS-C catalyzed regioselective monoacylation of the sophorolipid ethyl ester 1 at C-6".
  • Ethyl ester was treated at 40°C for 72 hr with an excess of vinyl acetate in dry THF using Lipase PS on a ceramic support (Lipase PS-C). This gave monoacetate 12, selectively modified at C-6", in 89% yield. 12 ([ ⁇ ] 25 D -9.67) was identified by an LC-APCI mass spectrum (m/z 715.51 [M+Na] + ) and detailed NMR spectral analyses.
  • This compound had 1 H NMR resonances similar to 12 except those that appeared at 1.93 (s), 5.63(s), and 6.11 (s) ppm in 13 due to replacement of an acetyl group in 12 by a methacryl group at C-6".
  • the resonances in the 13 C NMR spectrum of 13 at 18.56, 126.43, 137.85, and 168.67 ppm further support the presence of a methacryl moiety in the molecule.
  • the 13 C NMR showed a significant downfield shift for C-6" (from 62.77 ppm in ethyl ester to 65.15 ppm in 13), an upfield shift for the C-5"-signal, and no change for C-2'. Therefore, it was concluded that lipase PS-C is an excellent catalyst for highly regioselective acylation of ethyl ester at C-6" using vinyl acetate or vinyl methacrylate.
  • Enzyme Screening for amidation reaction For amidation of ethyl ester with primary amines (tyramine, phenethylamine, p-methoxyphenethylamine, 2-(p-tolyl)ethylamine, p- fluorophenethylamine), different lipases (PPL, CCL, PS-30, AK, MAP-10, Novozyme 435, and Lipozyme IM) in dry organic solvent at different temperatures (room temperature, 30°, 40° and 50°C) were evaluated. Only Novozyme 435 was able to catalyze the formation of amide in high yield. A preferable condition for the reaction was in dry THF at 50°C for 24 hr. Amidation did not occur when the lipases other than Novozyme 435 were used.
  • primary amines tyramine, phenethylamine, p-methoxyphenethylamine, 2-(p-tolyl)ethylamine,
  • Novozyme 435 catalyzed amidation of sophorolipid ethyl ester.
  • Novozyme 435 was used to catalyze mild amidation reactions between primary amines (tyramine, phenethylamine, p-methoxyphenethylamine, 2-(p- tolyl)ethylamine, p-fluorophenethylamine) and the sophorolipid ethyl ester.
  • primary amines tyramine, phenethylamine, p-methoxyphenethylamine, 2-(p- tolyl)ethylamine, p-fluorophenethylamine
  • the 13 C NMR spectrum of 14 showed the absence of resonances for O-CH 2 CH3 of ethyl ester. Instead, carbons corresponding to the tyramine amide moiety were found at positions that correspond with the expected product structure.
  • the retention of the disaccharide structure for 14 was evident by study of the sugar ring protons and carbons.
  • the acetal carbons C-1' and C-1" showed signals at 102.82 and 104.75 ppm that are consistent with that expected based on comparisons to ethyl ester.
  • Novozyme 435 catalyzed the amidation of ethyl ester with tyramine to give 14.
  • Phenethyl 17-L-[(2'-0- ?-D-glucopyranosyl- ?-D-glucopyranosyl)-oxy]- cis-9-octadecenamide 15 was synthesized by the Novozyme 435-catalyzed amidation of ethyl ester with phenethylamine in dry THF at 50°C.
  • the resulting product 15 was purified by column chromatography over silica gel with methanol/chloroform (1 :9, v/v) as eluent with high yield (90%).
  • This optically active compound ([ ⁇ ] 25 D -13.93) showed 748.72 [M+Na] + and 726.72 [M+H] + ions peaks in the LC-APCI mass spectrum.
  • the 1 H NMR of the product did not have resonances corresponding to the -OCH 2 CH_ group for ethyl ester.
  • Novozyme 435 was an effective catalyst for the diacetylation of 14 at C-6' and C-6" and this compound was identified as p- Hydroxy phenethyl 17-L-[(2'-0- ?-D-glucopyranosyl-/?-D-glucopyranosyl)-oxy-cis- 9-octadecenamide-6',6"-diacetate.
  • This study also showed that the replacement of the ethyl ester group in ethyl ester by an amide group in 14 did not have a significant effect on the Novozyme 435 catalyzed regioselective acetylation of these substrates.
  • This compound had 1 H NMR resonances similar to 19 except those that appeared due to the replacement of acetyl groups in 19 by methacryl groups in 20 at positions C-6' and C-6". Relative to 19, the 13 C NMR of 20 showed downfield shifts of >2 ppm for the 6'- and 6"-carbons.
  • Novozyme 435 worked well for both amidation as well acylation, synthesis of 20 from ethyl ester by a one-pot two step process was attempted. First, the amidation of ethyl ester to form 14 was performed exactly as above. Subsequently, vinyl methacrylate was added in excess to the reaction without isolation of 14 or further change in the reaction conditions. By this method, 20 was obtained in high yield. Novozym 435-catalyzed regioselective monoacylation of 5 at 6'-position.
  • Novozyme 435 was an effective catalyst for the monacylation of 14 at C-6' and this compound was identified as p-Hydroxy phenethyl 17-L-[(2'-0 ⁇ ?-D-glucopyranosyl- ?-D- glucopyranosyl)-oxy]-cis-9-octadecenamide-6'-acetate. Therefore, Novozym 435 is not only an excellent catalyst for highly regioselective diacylation but also monoacylation at 6'-position of 14. The above reaction was further extended for the preparation of related monomethacrylated derivative.
  • This compound had 1 H NMR resonances similar to 23 except those that appeared due to replacement of an acetyl group in 23 by one methacryl group at 1.93 (3H, s), 5.62 (1 H, s), 6.11 (1 H, s) ppm in 23 at C-6".
  • the resonances in 13 C NMR spectrum of 24 at 18.57, 126.46, 137.84, 168.70 further supported the presence of a methacryl moiety in the molecule.
  • 13 C NMR showed significant downfield shift in C-6", upfield shift in C-5" but no change in C-2' was noticed.
  • Metheine, methylene and methyl groups were distinguished by a 13 C NMR DEPT spectrum of the molecule.

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Abstract

La présente invention concerne la préparation et l'utilisation de 17-L-[(2'-O-?-D-glucopyranosyl-?-D-glucopyranosyl)-oxy]-cis-9-octadecénoate, de cycle ouvert et Lactonique17-L-[(2'-O-?-D-glucopyranosyl-?-D-glucopyranosyl)-oxy]-cis-9-octadecénoate, Méthyle 17-L-[(2'-O-?-D-glucopyranosyl-?-D-glucopyranosyl)-oxy]-cis-9-octadecénoate, éthyle 17-L-[(2'-O-?-D-glucopyranosyl-?-D-glucopyranosyl)-oxy]-cis-9-octadecénoate, Hexyle 17-L-[(2'-O-?-D-glucopyranosyl-?-D-glucopyranosyl)-oxy]-cis-9-octadecénoate, éthyle 17-L-[2'-O-?-D-glucopyranosyl-?-D-glucopyranosyl)-oxy]-cis-9-octadecénoate-6''-acétate and éthyle 17-L-[(2'-O-?-D-glucopyranosyl-?-D-glucopyranosyl)-oxy]-cis-9-octadecenoate-6',6''-diacétate. Ces sophorolipides sont des agents antibactériens, antiviraux et/ou spermicides.
PCT/US2003/035871 2002-11-06 2003-11-06 Proprietes antimicrobiennes de diverses formes de sophorolipides WO2004044216A1 (fr)

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AU2003299557A AU2003299557A1 (en) 2002-11-06 2003-11-06 Antimicrobial properties of various forms of sophorolipids
US11/020,683 US20050164955A1 (en) 2003-11-06 2004-12-22 Antifungal properties of various forms of sophorolipids

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005089522A2 (fr) 2004-03-19 2005-09-29 Gross Richard A Proprietes spermicides et virocides de differentes formes de sophorolipides
WO2006069175A2 (fr) 2004-12-22 2006-06-29 Polytechnic University Proprietes antifongiques de diverses formes de sophorolipides
EP1729782A2 (fr) * 2004-03-24 2006-12-13 Polytechnic University Traitement et prophylaxie d'une sepsie et d'un choc septique
EP1953237A1 (fr) * 2007-02-01 2008-08-06 Ecover N.V. Procédé de production de glycolipides en chaînes courtes
CN101199539B (zh) * 2007-12-10 2010-04-14 山东大学 槐糖脂在制备抗皮肤癣菌药物中的应用
WO2010050413A1 (fr) 2008-10-28 2010-05-06 株式会社カネカ Procédé pour produire le lipide sophorose
WO2011154523A1 (fr) 2010-06-11 2011-12-15 Universiteit Gent Souches de levures dont la production de sophorolipides est modifiée et leurs utilisations
CN102492605A (zh) * 2011-11-30 2012-06-13 中海石油环保服务（天津）有限公司 生物反应器及其连续生产槐糖脂的方法
WO2012080116A1 (fr) 2010-12-15 2012-06-21 Universiteit Gent Production de sophorolipides non acétylés par fermentation
WO2012167815A1 (fr) * 2011-06-06 2012-12-13 Ecover Co-Ordination Center N.V. Compositions de sophorolactone et leurs utilisations
EP2555620A1 (fr) * 2010-04-05 2013-02-13 Polytechnic Institute of New York University Compositions d'analogues de sophorolipides
WO2013092421A1 (fr) * 2011-12-20 2013-06-27 Universiteit Gent Lactonase dérivée de candida bombicola et ses utilisations
EP2764006A1 (fr) * 2011-10-04 2014-08-13 Polytechnic Institute of New York University Sophorolipides modifiés pour l'inhibition de phytopathogènes
WO2019020578A1 (fr) 2017-07-25 2019-01-31 Dsm Ip Assets B.V. Utilisation de sophorolipides en tant qu'additif pour alimentation animale
US10287615B2 (en) 2011-06-06 2019-05-14 Ecover Co-Ordination Center N.V. Sophorolactone production
EP3569689A4 (fr) * 2017-01-31 2020-11-11 Saraya Co., Ltd. Composition de cryoconservation de cellules et procédé de cryoconservation
CN115947770A (zh) * 2022-12-26 2023-04-11 安徽省森湶谷药业股份有限公司 新的百蕊草苷化合物及其应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BISHT K.S. ET AL.: "Enzyme-mediated regioselective acylations of sophorolipids", JOURNAL OF ORGANIC CHEMISTRY, vol. 64, 14 January 1999 (1999-01-14), pages 780 - 789, XP002976149 *
SINGH S.K. ET AL.: "Regioselective enzyme-catalyzed synthesis of sophorolipid esters, amides and multifunctional monomers", JOURNAL OF ORGANIC CHEMISTRY, vol. 68, 7 June 2003 (2003-06-07), pages 5466 - 5477, XP002976150 *

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EP1750726A4 (fr) * 2004-03-19 2010-06-16 Richard A Gross Proprietes spermicides et virocides de differentes formes de sophorolipides
WO2005089522A2 (fr) 2004-03-19 2005-09-29 Gross Richard A Proprietes spermicides et virocides de differentes formes de sophorolipides
EP1750726A2 (fr) * 2004-03-19 2007-02-14 GROSS, Richard A. Proprietes spermicides et virocides de differentes formes de sophorolipides
EP1729782A2 (fr) * 2004-03-24 2006-12-13 Polytechnic University Traitement et prophylaxie d'une sepsie et d'un choc septique
EP1729782A4 (fr) * 2004-03-24 2010-11-10 Polytechnic Inst Of New York U Traitement et prophylaxie d'une sepsie et d'un choc septique
EP2402014A3 (fr) * 2004-03-24 2012-02-15 Polytechnic Institute of New York University Utilisation de sophorolipides synthétisés par fermentation de Candida bombicola
WO2006069175A2 (fr) 2004-12-22 2006-06-29 Polytechnic University Proprietes antifongiques de diverses formes de sophorolipides
EP1838864A2 (fr) * 2004-12-22 2007-10-03 Polytechnic University Proprietes antifongiques de diverses formes de sophorolipides
EP1838864A4 (fr) * 2004-12-22 2011-10-12 Univ Polytechnic Proprietes antifongiques de diverses formes de sophorolipides
EP1953237A1 (fr) * 2007-02-01 2008-08-06 Ecover N.V. Procédé de production de glycolipides en chaînes courtes
CN101199539B (zh) * 2007-12-10 2010-04-14 山东大学 槐糖脂在制备抗皮肤癣菌药物中的应用
WO2010050413A1 (fr) 2008-10-28 2010-05-06 株式会社カネカ Procédé pour produire le lipide sophorose
US8664373B2 (en) 2008-10-28 2014-03-04 Kaneka Corporation Method for producing sophorose lipid
EP2555620A1 (fr) * 2010-04-05 2013-02-13 Polytechnic Institute of New York University Compositions d'analogues de sophorolipides
EP2555620A4 (fr) * 2010-04-05 2013-10-23 Politechnic Inst Univ New York Compositions d'analogues de sophorolipides
WO2011154523A1 (fr) 2010-06-11 2011-12-15 Universiteit Gent Souches de levures dont la production de sophorolipides est modifiée et leurs utilisations
WO2012080116A1 (fr) 2010-12-15 2012-06-21 Universiteit Gent Production de sophorolipides non acétylés par fermentation
US10287615B2 (en) 2011-06-06 2019-05-14 Ecover Co-Ordination Center N.V. Sophorolactone production
US9795131B2 (en) 2011-06-06 2017-10-24 Ecover Co-Ordination Center N.V. Sophorolactone compositions and uses thereof
WO2012167815A1 (fr) * 2011-06-06 2012-12-13 Ecover Co-Ordination Center N.V. Compositions de sophorolactone et leurs utilisations
EP2764006A1 (fr) * 2011-10-04 2014-08-13 Polytechnic Institute of New York University Sophorolipides modifiés pour l'inhibition de phytopathogènes
EP2764006A4 (fr) * 2011-10-04 2014-12-10 Politechnic Inst Univ New York Sophorolipides modifiés pour l'inhibition de phytopathogènes
CN102492605A (zh) * 2011-11-30 2012-06-13 中海石油环保服务（天津）有限公司 生物反应器及其连续生产槐糖脂的方法
US9388443B2 (en) 2011-12-20 2016-07-12 Universiteit Gent Lactonase derived from Candida bombicola and uses thereof
US9394559B2 (en) 2011-12-20 2016-07-19 Universiteit Gent Lactonase derived from candida bombicola and uses thereof
WO2013092421A1 (fr) * 2011-12-20 2013-06-27 Universiteit Gent Lactonase dérivée de candida bombicola et ses utilisations
EP3569689A4 (fr) * 2017-01-31 2020-11-11 Saraya Co., Ltd. Composition de cryoconservation de cellules et procédé de cryoconservation
WO2019020578A1 (fr) 2017-07-25 2019-01-31 Dsm Ip Assets B.V. Utilisation de sophorolipides en tant qu'additif pour alimentation animale
CN115947770A (zh) * 2022-12-26 2023-04-11 安徽省森湶谷药业股份有限公司 新的百蕊草苷化合物及其应用

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