[go: up one dir, main page]

EP0615520A1 - Optisch-aktive lactone - Google Patents

Optisch-aktive lactone

Info

Publication number
EP0615520A1
EP0615520A1 EP93920787A EP93920787A EP0615520A1 EP 0615520 A1 EP0615520 A1 EP 0615520A1 EP 93920787 A EP93920787 A EP 93920787A EP 93920787 A EP93920787 A EP 93920787A EP 0615520 A1 EP0615520 A1 EP 0615520A1
Authority
EP
European Patent Office
Prior art keywords
formula
lactones
optically active
enzyme
decalactone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP93920787A
Other languages
English (en)
French (fr)
Inventor
Jean-Paul Bourdineaud
Charles Ehret
Martin Petrzilka
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Givaudan SA
Original Assignee
Givaudan Roure International SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Givaudan Roure International SA filed Critical Givaudan Roure International SA
Priority to EP93920787A priority Critical patent/EP0615520A1/de
Publication of EP0615520A1 publication Critical patent/EP0615520A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D315/00—Heterocyclic compounds containing rings having one oxygen atom as the only ring hetero atom according to more than one of groups C07D303/00 - C07D313/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/24—Synthetic spices, flavouring agents or condiments prepared by fermentation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/30—Oxygen atoms, e.g. delta-lactones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B9/00—Essential oils; Perfumes
    • C11B9/0069—Heterocyclic compounds
    • C11B9/0073—Heterocyclic compounds containing only O or S as heteroatoms
    • C11B9/008—Heterocyclic compounds containing only O or S as heteroatoms the hetero rings containing six atoms
    • 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
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/02—Oxygen as only ring hetero atoms
    • C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
    • 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
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • C12Y301/01—Carboxylic ester hydrolases (3.1.1)
    • C12Y301/01003—Triacylglycerol lipase (3.1.1.3)

Definitions

  • the present invention provides an enzymatic process for the preparation of the compounds of formula I, which are strongly enriched in either the R- or the S-enantiomer, i.e. exhibiting optical purities of at least 50% ee.
  • the invention relates also to the utilization of compounds of formula I so obtained as perfuming or flavoring ingredients.
  • n stands for zero or 1
  • (-)-(R)- ⁇ -jasmine lactone 3b is found in jasmine oil [Winter M. et al., Helv. Chim. Acta. 45, 1250, 1962], whereas its (+)-(S) counterpart 3a is found in tuberose oil [Kaiser R., and Lamparsky D., Tetrahedron Lett. 20 , 1659, 1976] together with (-)- (R)-tuberolactone 6a, (-)-(R)-masso ⁇ alactone 5a, and (+)-(R)- ⁇ -decalactone 2a.
  • ⁇ -Jasmine lactone (Z-dec-7-en-4-olide) of unspecified absolute configuration was found in jasmine oil
  • (+)-(S)-tuberolactone 6b and (+)-(S)-masso ⁇ alactone 5b has not been described in the literature. Actually, more and more examples become known, where the two enantiomeric forms of chiral
  • both optically active forms of masso ⁇ alactone and tuberolactone were obtained by chemical transformation of the corresponding optically active ⁇ -decalactones and ⁇ -jasmine lactones.
  • tuberolactone could not be resolved enzymatically under the usually applied conditions.
  • the principle of the enzymatic resolution of racemic lactones is as follows: the enzyme and the racemic lactone are treated, e.g. stirred in a buffered reaction medium, namely in a pH-range of ca. 6.8 to ca. 7.8, preferably at pH 7.2, whereupon stereoselective hydrolysis of the internal ester bond of one of the enantiomers occurs.
  • a buffered reaction medium namely in a pH-range of ca. 6.8 to ca. 7.8, preferably at pH 7.2
  • the course of the reaction may be followed with the help of a pH-meter, and subsequent addition of alkali allows
  • the enzyme spared enantiomer is, conveniently, extracted with an organic solvent, whereas the enzyme-hydrolyzed
  • enantiomer remains in the basic aqueous phase ; the latter may then be retrieved by solvent extraction after
  • Suitable solvents for this process are hexane,
  • cyclohexane methyl-t-butyl ether, etc. preferably ethyl ether.
  • one or both of the separated enantiomers may preferably be subjected to a second cycle of enzyme-catalyzed hydrolysis in order to improve the enantiomeric excesses (e.g. for ⁇ -decalactone and ⁇ -jasmine lactone).
  • a second cycle of enzyme-catalyzed hydrolysis in order to improve the enantiomeric excesses (e.g. for ⁇ -decalactone and ⁇ -jasmine lactone).
  • ⁇ -jasmine lactone a single cycle allowed to reach a high enantiomeric excess (88%).
  • ⁇ -jasmine-lactone are preferable used the buffer and enzymes described by Blanco et al.. Tetrahedron Lett., 29 (16),
  • the enzymes used were of esterase type, whereby said term also encompasses lipases, more specifically horse liver esterase, pig pancreatic lipase or pig liver esterase, preferably horse liver esterase.
  • the alkali used for adjustment of the pH of the reaction medium were
  • centrifugation was preferred over filtration.
  • the solvents used for extraction were conveniently cyclic and aliphatic alkanes or ethers, preferably ethyl ether. After drying the combined organic phases over MgS ⁇ 4 and evaporation of the solvent, the crude lactones were purified by flash chromatography on silica gel and/or by distillation at reduced pressure. The resulting
  • enantiomerically enriched lactones were spectroscopically analyzed and organoleptically evaluated by a panel of perfumers.
  • ⁇ -decalactone as described by Blanco et al., which is, as pointed out above, inadequate for an industrial production (too slow, moderate enantiomeric excess)
  • horse liver esterase shows a higher affinity for 5-alkenyl- ⁇ -decalactones thereby inducing much higher enantioselectivities.
  • 5-alkenyl-substituted ⁇ -decalactones are much better substrates for this enzyme than ⁇ -decalactone itself.
  • enantiomerically enriched masso ⁇ alactone and tuberolactone can be prepared by converting optically active ⁇ -decalactone and ⁇ -jasmine lactone, respectively, to the corresponding allyl ß-oxoesters, which then in turn can be oxidatively decarboxylated using palladium acetate as catalyst (cf. Minami I., Nisar M., Yuhara M., Shimizu I., and Tsuji J., Synthesis, 992-998, 1987) Mercier C.,
  • optically active masso ⁇ alactone and tuberolactone were analytically and organoleptically characterized.
  • Solvent hexane, cyclohexane, tetrahydrofuran, MTBE, ethyl ether, etc., preferably cyclohexane.
  • Base sodium hydride, potassium hydride, potassium tert-butoxide, etc. preferably sodium hydride.
  • Catalyst a Palladium complex such as Pd (OAc) 2 -CH 3 CN,
  • Pd (OAc) 2 -PPh 3 Pd (OAc) 2 -dppe, preferably Pd (OAc) 2- CH 3 CN .
  • Solvent nitriles or dinitriles, e.g. acetonitrile,
  • Temp. ca. 20 to ca. 80°C, preferably 80°C, i.e.
  • jasmolactone and ⁇ -jasmine lactone were assessed via catalytic hydrogenation of their side chain double bonds and comparison of the optical rotation data of the
  • the art of preparing such odour or flavour compositions is well known to the skilled artisan.
  • the easy access to the individual isomers, i.e. the optically active lactones as enabled by the novel method opens new opportunitites if compared to the use of the corresponding racemates, in as fas as by blending one of these optically active lactones, preferably the (+) form for the ⁇ -lactones and the (-) form for the ⁇ -lactones, the final composition can be targeted: by adding the racemate, or the + form, or the - form to one and the same basic composition, the optimum formulation can easily be
  • perfume compositions can be used in perfumes, soaps, shampoos, detergents, cosmetics, etc. and the flavor compositions in foodstuffs, drinks, etc.
  • Mass spectra were recorded on a FINNIGAN 4500 instrument (ionization voltage : 70 eV, acceleration voltage : 1500V, ion source temperature : 150°C).
  • Chiral Gas chromatography was carried out on a PERKIN ELMER 8500 apparatus equipped with a FID-detector and a Lipodex E (MACHEREY-NAGEL) capillary column (25m ⁇ 0.25mm i.d., isotherm 140°C, carrier gas : 0.7ml/min.). Retention times (Rt) are given in minutes.
  • the potassium phosphate buffer (“KPO 4 " buffer) was obtained by addition of 0.1M KH 2 PO 4 to 0.1M K 2 HPO 4 until the pH of 7.2 was reached.
  • G -MS 170(M + ,0), 152(2), 114(10), 99(100), 71(35), 55(33), 42(40).
  • (+)-(R)- ⁇ -decalactone 2a was obtained after one cycle of enzyme-catalyzed hydrolysis via the enzyme hydrolyzed isomer (cf. Scheme 1).
  • the reaction was carried out as described in example 1, using 200ml of 0.1M "KPO 4 " buffer, 9g of horse liver esterase and 18g (106 mmol) of racemic ⁇ -decalactone 1a
  • (+)-(R)- ⁇ -jasmine lactone 3b was obtained after one cycle of enzyme-catalyzed hydrolysis via the enzyme-spared isomer (cf . Scheme 1).
  • the reaction was carried out as described in example 1, using 200ml of 0.1M "KPO 4 " buffer, 10g of horse liver esterase and 20g (119 mmol) of racemic ⁇ -jasmine lactone 1b (cf. Utaka M. et al., J. Org. Chem., 51, 935-38, 1986 or refs cited therein).
  • 2h 20min. (4h 30min. if sodium phosphate buffer is used) when the hydrolysis had reached a conversion of 50%, extraction followed by distillation at reduced pressure (140°C/ 0.4mmHg)
  • IR (cm -1 ) 726, 933, 1047, 1132, 1159, 1183, 1242, 1340, 1362, 1383, 1444, 1463, 1737, 2877, 2935, 2962, 3012.
  • IR (cm -1 ) 931, 968, 1045, 1181, 1242, 1333, 1343, 1376, 1445, 1736, 2856, 2885, 2922, 2940, 3018.
  • (+)-(S)-tuberolactone 6b was prepared by starting from (-)-(R)- ⁇ -jasmine lactone 3b as described in example 3.
  • (+)-(S)-masso ⁇ alactone 5b was prepared by starting from (-)-(S)- ⁇ -decalactone 2b (3.4g, 20 mmol), which was obtained as described in example 1, and by following the procedure given for (+)-(S)-tuberolactone 6b (example 5).
  • IR (cm -1 ) 816, 954, 1040, 1058, 1119, 1158, 1252, 1387, 1465, 1726, 2862, 2933, 2956
  • (+)-(R)- and (-)-(S)- ⁇ -jasmine lactones were obtained after two cycles of enzyme-catalyzed hydrolysis in 10% CaCl 2 (cf. Scheme 2).
  • (+)-(R)- ⁇ -jasmine lactone 9a and the yield of (-)-(S)- ⁇ -jasmine lactone 9b a second hydrolysis cycle was carried out. Accordingly the above obtained 660mg of (+)-(R)- ⁇ -jasmine lactone 9a were added to a mixture of 8ml of 10% CaCl 2 (pH adjusted to 7.2) and 1g of porcine pancreatic lipase under stirring while maintaining the pH at 7.2 by controlled addition of 2M NaOH. After 5 hours, the hydrolysis leveled off at a conversion of 21%. Work-up was carried out as described for the first cycle.
  • (+)-(R)- and (-)-(S)- ⁇ -decalactones were obtained starting from racemic ⁇ -decalactone after two cycles of enzyme-catalyzed hydrolysis as described in example 7. After 24 hours of reaction the hydrolysis leveled off at a
  • IR (cm -1 ) 913, 967, 1022, 1127, 1183, 1218, 1352, 1463, 1778, 2859, 2932, 2956.
  • Fragrance compositions of the floral, fruity and peachy type were prepared according to the following scheme (the parts are by weight) :
  • fragrance composition A containing optically active (-)-(S)- ⁇ -decalactone 2b is considerably stronger and much more peachy with a sweeter and a more lactonic effect than fragrance B, which instead contains the corresponding racemate 2a/2b.
  • Fragrance compositions of a floral, jasmine like and fruity type were prepared according to the following scheme (parts by weight) :
  • fragrance composition A containing optically active (-)-(R)- ⁇ -jasmine lactone 3b has a clear-cut fruity, apricot, frangipane and dry fruit like odour with a much more characteristic jasmine note than
  • fragrance B which instead contains the corresponding racemate 3a/3b. Simultaneously the strength and intensity of the lactonic base note in composition A have also been clearly improved.
  • Fragrance compositions of a floral, tuberose type were prepared according to the following scheme (parts by weight) :
  • fragrance composition A containing optically active (-)-(R)-jasmolactone 4b exhibits a much stronger floral note with more freshness towards a lighter tuberose note than fragrance B, which instead contains the corresponding racemate 4a/4b.
  • Apricot flavours were prepared according to the following scheme (parts by weight) :
  • flavour A containing optically active (-)-(S)- ⁇ -decalactone 2b is much more fruity, more
  • flavour A containing optically active (-)-(R)- ⁇ -jasmine lactone 3b is more fruity, more

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Polymers & Plastics (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Fats And Perfumes (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Cosmetics (AREA)
  • Furan Compounds (AREA)
  • Pyrane Compounds (AREA)
EP93920787A 1992-09-29 1993-09-21 Optisch-aktive lactone Withdrawn EP0615520A1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP93920787A EP0615520A1 (de) 1992-09-29 1993-09-21 Optisch-aktive lactone

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP92810732 1992-09-29
EP92810732 1992-09-29
EP93920787A EP0615520A1 (de) 1992-09-29 1993-09-21 Optisch-aktive lactone
PCT/EP1993/002554 WO1994007887A1 (en) 1992-09-29 1993-09-21 Optically active lactones

Publications (1)

Publication Number Publication Date
EP0615520A1 true EP0615520A1 (de) 1994-09-21

Family

ID=8211996

Family Applications (1)

Application Number Title Priority Date Filing Date
EP93920787A Withdrawn EP0615520A1 (de) 1992-09-29 1993-09-21 Optisch-aktive lactone

Country Status (3)

Country Link
EP (1) EP0615520A1 (de)
JP (1) JPH07502285A (de)
WO (1) WO1994007887A1 (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4700867B2 (ja) * 2001-09-27 2011-06-15 花王株式会社 新規化合物及び用途
JP4323271B2 (ja) 2002-09-27 2009-09-02 花王株式会社 バレロラクトン化合物及び香料組成物
WO2004106320A1 (ja) * 2003-05-28 2004-12-09 Zeon Corporation 光学活性ラクトン類の製造方法
GB0506263D0 (en) * 2005-03-29 2005-05-04 Givaudan Sa Skin lightening methods, composition and products
US10149830B2 (en) 2016-06-03 2018-12-11 Cushing Academy Pharmaceutical agents and methods relating thereto
JP6953677B2 (ja) * 2018-03-06 2021-10-27 曽田香料株式会社 果実風味改善剤
WO2023232241A1 (en) * 2022-06-01 2023-12-07 Symrise Ag 5,5-disubstitued tetrahydrofuran-2-one as fragrance compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9407887A1 *

Also Published As

Publication number Publication date
WO1994007887A1 (en) 1994-04-14
JPH07502285A (ja) 1995-03-09

Similar Documents

Publication Publication Date Title
Fortunati et al. Chemoenzymatic preparation of musky macrolactones
Davoli et al. Stereoselective synthesis of fluorinated β-aminoacids from ethyl trans-N-benzyl-3-trifluoromethylaziridine-2-carboxylate
EP0615520A1 (de) Optisch-aktive lactone
Abate et al. Biocatalysed synthesis of the enantiomers of the floral odorant Florhydral®
Aleu et al. Lipase-mediated synthesis of the enantiomeric forms of 4, 5-epoxy-4, 5-dihydro-α-ionone and 5, 6-epoxy-5, 6-dihydro-β-ionone. A new direct access to enantiopure (R)-and (S)-α-ionone
Serra et al. Enzyme‐Mediated Preparation of Enantiomerically Pure p‐Menthan‐3, 9‐diols and Their Use for the Synthesis of Natural p‐Menthane Lactones and Ethers
Abate et al. Preparation of the enantiomerically enriched isomers of the odorous cyclic ethers Clarycet®, Florol®, and Rhubafuran® by enzymatic catalysis
JP5026276B2 (ja) γ−ウンデセノラクトン、化粧品としての及び食品添加物の形態における、その生産方法及び使用方法
US7196050B2 (en) Unsaturated ester as perfuming ingredient
EP0378825B1 (de) Alicyclische Ester und ihre Anwendung als Riechstoffkomponenten
JPH0889282A (ja) 立体異性アルコール混合物の分解方法
Asamitsu et al. Synthesis and Odor Description of Both Enantiomers of Methyl 4, 5‐Didehydrojasmonate, a Component of Jasmin Absolute
Barnier et al. Chemo-enzymatic preparation of optically active endo-bicyclo [4.1. 0] heptan-2-ols
Luparia et al. Enantioselective synthesis and olfactory evaluation of 13‐alkyl‐substituted α‐ionones
Brenna et al. Enzyme‐Mediated Preparation of (+)‐and (−)‐β‐Irone and (+)‐and (−)‐cis‐γ‐Irone from Irone alpha®
Kawasaki et al. Lipase-catalyzed preparation of optically active isomers of cyclamen aldehyde
Ferraboschi et al. A chemoenzymatic synthesis of enantiomerically pure (R)-and (S)-2-methyldecan-1-ol
Kawasaki et al. Lipase-mediated preparation of optically active isomers of Rosaphen®
Brenna et al. Enzyme‐mediated preparation of the single enantiomers of the olfactory active components of the woody odorant Timberol®
SUEMUNE et al. Enzymatic procedure for the synthesis of 11-deoxyprostaglandins
EP3280704B1 (de) Verfahren zur synthese eines vorläufers eines einzigen milch-lacton-isomers
JP2000327631A (ja) 新規マロネートおよびその製法
Sakauchi et al. Enzymatic resolution and odor description of both enantiomers of lavandulol, a fragrance of lavender oil
JP4859826B2 (ja) フレグランス組成物の製造に好適な三置換フラン
Kurosawa et al. Pheromonal and kairomonal activities can be separated: synthesis and bioactivity studies of pine bast scale sex pheromones and their analogues

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19940520

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): CH DE ES FR GB IT LI NL

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19970402