DK142170B - Analogifremgangsmåde til fremstilling af terpenophenoler. - Google Patents
Analogifremgangsmåde til fremstilling af terpenophenoler. Download PDFInfo
- Publication number
- DK142170B DK142170B DK154075AA DK154075A DK142170B DK 142170 B DK142170 B DK 142170B DK 154075A A DK154075A A DK 154075AA DK 154075 A DK154075 A DK 154075A DK 142170 B DK142170 B DK 142170B
- Authority
- DK
- Denmark
- Prior art keywords
- ppm
- solution
- terpenophenols
- preparation
- phenol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 13
- -1 5-camphyl Chemical group 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 claims 1
- 241000700159 Rattus Species 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000002924 anti-infective effect Effects 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 239000012678 infectious agent Substances 0.000 claims 1
- 239000000829 suppository Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 230000001988 toxicity Effects 0.000 claims 1
- 231100000419 toxicity Toxicity 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 230000003385 bacteriostatic effect Effects 0.000 description 6
- 244000005700 microbiome Species 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- DTLTUUJDCNTTSN-UHFFFAOYSA-N 1,4-dioxane;molecular bromine Chemical compound BrBr.C1COCCO1 DTLTUUJDCNTTSN-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 3
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- NYYGACIUGBJQHR-UHFFFAOYSA-N 5-methyl-2-(4,7,7-trimethyl-3-bicyclo[2.2.1]heptanyl)phenol Chemical compound OC1=CC(C)=CC=C1C1C(C2(C)C)(C)CCC2C1 NYYGACIUGBJQHR-UHFFFAOYSA-N 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- GSQACUNMFGRAKY-UHFFFAOYSA-N bromine;1,4-dioxane Chemical compound [Br].C1COCCO1 GSQACUNMFGRAKY-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- RNRHMQWZFJXKLZ-XUWXXGDYSA-N xibornol Chemical compound C1=C(C)C(C)=CC(O)=C1[C@H]1[C@](C2(C)C)(C)CC[C@@H]2C1 RNRHMQWZFJXKLZ-XUWXXGDYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/12—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings
- C07C39/17—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings containing other rings in addition to the six-membered aromatic rings, e.g. cyclohexylphenol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
- C07C37/14—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms by addition reactions, i.e. reactions involving at least one carbon-to-carbon unsaturated bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/62—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/24—Halogenated derivatives
- C07C39/42—Halogenated derivatives containing six-membered aromatic rings and other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Oncology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Description
(11) FREMLÆGGELSESSKRIFT 1 ^21 70 DANMARK <«>lm.CI.· 0 07 C 39/42 f(21) Ansøgning nr. 1540/75 (22) Indleveret den 10. apr. 1975 (24) Løbedag 10. apr. 1975 (44) Ansøgningen fremlagt og fremlseggelseeskriftet offentliggjort den 15· SCP · 1 9')0
DIREKTORATET FOR
PATENT-OG VAREMÆRKEVÆSENET (30) Prioritet begæret fra den
11. apr. 1974, 1β142/74, GB
(71> MAR-PHA S.A. SOCIETE D» ETUDE ET D1EXPLOITATION DE MARQUES, 7, rue Biscornet, 75012 Paris, PR.
{72} Opfinder: Jean Mardiguian, 7# rue Biscornet, 75012 Paris, PR.
(74) Fuldmægtig under sagens behandling:
Ingeniørfirmaet Hofman-Bang & Boutard.
(54) Analogifremgangsmåde til fremstilling af terpenophenoler.
Den foreliggende opfindelse angår en analogifremgangsmåde til fremstilling af hidtil ukendte terpeno-phenoler med den i kravets indledning anførte almene formel, hvilken fremgangsmåde er ejendommelig ved det i kravets kendetegnende del anførte.
De omhandlede forbindelser har interessante bakteriostatiske egenskaber, og de er nyttige ved behandling af infektioner forårsaget af grampositive og gramnegative mikroorganismer britisk patentskrift nr. 1.305.217 omtales isobornylphenoler og disses methylestere, der også udviser bakteriostatiske egenskaber.
Disse forbindelser har dog som påvist nedenfor ikke i samme udstrækning virkning over for såvel gramnegative som grampositive bakterier, således som det er tilfældet ved de her omhandlede forbindelser.
2 142170
Det ved fremgangsmåden Ifølge opfindelsen anvendte brom-dioxan-komplex er fortrinsvis dioxan-dibromid, og reaktionen gennemføres fortrinsvis i kulden i et ethylethermiljø, ved temperaturer, der er lavere end eller lig med omgivelsestemperaturen, isser 0-10°C. Fremgangsmåden ifølge opfindelsen illustreres nærmere ved nedenstående eksempler.
EKSEMPEL 1 i f
Br 2-Isobornvl-4-brom-5-methyl-phenol 3
Til en opløsning af 30 g 2-isobornyl-5-methyl-phenol i 200 cm ethylether, der er afkølet til 5°C sættes under omrøring langsomt 3,06 g dioxan-dibromid, idet man sørger for at temperaturen i reaktionsmediet ikke overstiger 10°C. Efter tilsætningen lader man reaktionsblandingen henstå ved omgivelsestemperaturen natten over. Derefter udvaskes den organiske fase successivt med en vandig natriumchloridopløsning, 10% natriumbicarbonat og endelig med vand. Efter tørring og afdampning af etheren krystalliserer man remanensen fra pentan, og derpå fra isooctan, hvorved man opnår 21,4 g af det rene produkt, snip. 89-90°C.
Analyse for C-jjHgjOBr (molvægt 322,9) C% H% Br%
Ber: 63,18 7,12 24,74
Fundet ; 63 7,2 24,5 IR-spektrum I en opløsning i carbontetrachlorid i en koncentreration på 0,1 M/l observerer man følgende karakteristiske bånd: frit OH : 36ΟΟ cm"1
Aromatisk ring : 1615, 1505
Isobornyl : 28,50, 2880; 1470-1460 3 142170 NMR- spektrum I en opløsning i deutereret chloroform med TMS som reference, observerer man: CH^ brohoved 0,78 ppm singlet CH^ tvillinger 0,82 og 0,85 ppm singletter -CH (exo) 3,03 ppm triplet i H aromatisk 6,6 og 7,4 ppm singletter OH 4,7 ppm EKSEMPEL 2
- OH
(K>
Br 2-Isobornyl-4 brom-phenol
Til en opløsning af 10 g o-isobomylphenol i 100 c nr ethylether, der er afkølet til 5°C sættes langsomt under omrøring 10,8 g dioxan-dibromid, idet man holder reaktionsmediets temperatur mellem 5 og 10°C. Efter tilsætning lader man blandingen henstå ved omgivelsestemperaturen natten over. Derpå udvasker man successivt med en natriumchloridopløsning, en 10# natriumbicarbonatopløsning, og derpå med vand. Den organiske fase tørres, hvorpå etheren afdampes. Remanensen destilleres under reduceret tryk, og man opsamler fraktionen, som går over ved 183°C ved 3 mm. Ved krystallisation fra isooctan opnår man 9 g af et rent produkt med en hvid farve.
Smp. 81°C.
Analyse for C1gH210Br (m.v, 308,9) C# H# Br#
Ber: 63,15 6,80 25,86
Fundet: 62,2 6,7 25,6 4 142170 IR-spektrum I en dispersion i KBr, observerer man følgende karakteriske bånd: frit OH : 3560 cm"1
Aromatisk ring : 1600, 1500, 890, 820
Isobornyl : 2880, 2950, 1470, 1480 HMR-spektrum I deutereret chloroform med TMS som reference, observerer man især: CHj brohoved 0,75 ppm singlet CH-j tvillinger 0,8 og 0,82 ppm singletter -C-H (exo) 3,05 ppm triplet i OH 4,6 ppm EKSEMPEL 3 χπδ
Br 2-Isocamphyl-4-brom-phenol
Til en opløsning af 8 g o-isocamphylphenol i 50 cnr ethylether, der er afkølet til 5°C sættes 8,6 g dioxan-dibromid under omrøring, idet man sørger for at reaktionsmediets temperatur ikke overstiger 10°C. Man lader derpå blandingen henstå ved omgivelsestemperaturen natten over.
Man udvasker etherfasen successivt med en opløsning af natrium-chlorid, 10% natriumbicarbonat, natriumchlorid og derpå med vand.
Man tørrer over magnesiumsulfat og afdamper etheren under reduceret 5 142170 tryk. Remanensen krystalliseres fra isooctan. Efter tre krystallisationer opnår man 2 g af det rene produkt. Smp. 67°C.
Analyse for C]_6H21Br0 (molvæSt 309,25) C# Wi Br%
Bert 62,1 6,8 25,9
Fundet? 62,7 6,8 25,7 IR»spektrum I en dispersion i KBr, observerer man følgende karakteristiske bånd:
Isocamphyl : 2900, 2950 cm”1
Aromatisk ring : 1600, 1500, 820 OH : 3605 (i CCl^) NMR- spektrum I deutereret chloroform observerer man i forhold til TMS:
Isocamphyl: CH^ 0,085 ppm dubletter CH^ 0,9 og 1 ppm singletter OH 5 ppm EKSEMPEL 4 Γ
Crp
Br
Exo-2-norbornyl-4-brom-phenol
Til en opløsning af 40 g exo-2-norbornyl-phenol (0,21 mol) i 200 cm·^ ethylether, der er afkølet til 0°C sættes langsomt i løbet af 15 minutter 53 g (0,21 mol) dioxan-dibromid. Efter omrøring ved omgivelsestemperaturen i 1 time udvasker man successivt etherfasen med natriumchloridopløsning, derpå med en natrium-bicarbonatopløsning, og derpå med vand indtil neutralitet. Man tørrer over natriumsulfat, inddamper i vakuum, hvorpå manefestille- 6 142170 rer ved reduceret tryk. Man opsamler fraktionen, der går over ved 150°C ved 1 mm og opnår således 35 g af en farvet olie, der størk ner.
Analyse for C-^H-^OBr (molvægt 267,17) C% Br%
Ber: 58,44 5,66 29,91
Fundet: 58,20 5,52 29,90 IR-spektrum I form af en film observerer man følgende karakteristiske bånd:
Norbornyl : 2870, 2950, 1475 cm“^ OH : 3550, 3440 cm-1 NMR-spektrum I opløsning i dimethylsulfoxid observerer man med TMS som reference:
Norbornyl endo-proton 2,9 ppm (triplet) andre protoner 1,5 ppm (massiv) 9,5 ppm (singlet) OH 6,7 - 7,10 - 7,15 ppm EKSEMPEL 5
OH
Br
Exo-2-norbornyl-4-brom-5-methyl-phenol
Til en opløsning af 80 g exo-2-norbornyl-5-methyl-phenol (0,4 mol) i 400 crn^ vandfri ether, der er afkølet til 0°C , sættes langsomt 100 g (0,4 mol) dioxan-dibromid, idet man sørger for at temperaturen ikke overstiger 5°C. Efter omrøring i 1 time udvasker man etherfa- 7 142170 sen successivt med en natriumchloridopløsnlng, en natriumbicarbo-natopløsning og derpå med vand indtil neutralitet. Man tørrer over natriumsulfat, hvorpå man afdamper opløsningsmidlet i vakuum. Remanensen krystalliseres fra pentan ved 20°C. Man opnår 82 g af det rene produkt. Smp. 80°C.
Analyse for C-^H^OBr (molvægt 281,20) C% H# Br$
Ber: 59,80 6,08 28,42
Fundet: 59,91 6,00 28,57 IR-spektrum I en dispersion i KBr er de væsentlige absorptionsbånd følgende:
Norbomyl : 2950 , 2870, 1455 cm"·1· OH : 3200 cm-1
Aromatisk ring : 1615, 1500 cm“^ NMR- spektrum I en opløsning i dimethylsulfoxid observerer man med TMS som reference:
Norbornyl CH2 1,4 ppm (massiv H endo 2,35 ppm (triplet) OH 9,58 ppm (singlet) aromatiske protoner 6,72-7,15 ppm CH^ 2,2 ppm (singlet)
Bakteriostatisk virkning
Den bakteriostatiske virkning af de omhandlede phenoler er undersøgt ved udstrygningsmetoden på agarmedier. Denne metode består i at foretage stigende fortyndinger af det produkt, der skal undersøges, i næringsagar udhældt i petriskåle.
Disse agarmedier podes derpå i parallelle striber med de forskellige mikroorganismer, der skal undersøges, ved hjælp af et platinøje, der har været neddyppet i en 24 timer gammel kulturvæske inde g 142170 holdende hver mikroorganisme. Den bakteriostatiske dosis svarer til den laveste koncentration, ved hvilken mikroorganismen ikke udvikles langs podningsstriberne.
Man har undersøgt de omhandlede forbindelsers virkning overfor 2 grampositive mikroorganismer, nemlig Staphylococcus aureus og Streptococcus pyogenes, samt overfor 1 gramnegativ mikroorganisme, nemlig Escherichia coli. Man har endvidere undersøgt virkningen af den i Britisk patentskrift nr. 1 306 217 omtalte forbindelse 6-isobornyl-3,4-xylenol som kontrol.
Nedenstående tabel angiver de minimale hæmningskoncentrationer udtrykt i mg/1 for forbindelserne beskrevet i eksemplerne.
Minimal hæmningskoncentration (mg/1)
Forbindel- Staphylococcus Streptococcus Escherichia ser i eks. aureus_ pyogenes , coli_ 15 15 2 2 30 3 2,5 5 4 7,5 20 7,5 5 5 20 Kontrol: 6-isa- bornyl-3 , 4-xylenol 5 20 uvirksom ved 125
Af ovenstående tabel fremgår, at de i eksemplerne 4 og 5 beskrevne forbindelser, nemlig exo-2-norbornyl-4-brom-phenol samt exo-2-norbornyl-4-brom-5-methyl-phenol, udviser den særegenhed samtidigt at være virksom overfor grampositive og gramnegative bakterier, mens kontrolforbindelsen er uvirksom overfor gramnegative bakterier selv ved en så høj koncentration som 125 mg/1.
De i eksemplerne 1 til 3 omtalte forbindelser udviser en større bakteriostatisk virksomhed over for grampositive bakterier end kontrolforbindels en.
Claims (1)
- 9 142170 Toxicitet LD50 for de omhandlede forbindelser bestemt på mus og rotter er større end 1000 mg/kg. De omhandlede forbindelser er anvendelige som antiinfektiøse mid ler. Til dette formål kan de formuleres i en passende form til indgivelse ad oral eller rektal vej, såsom tabletter, kapsler og suppositorier, der indeholder 100-200 mg aktiv ingrediens, og som skal indgives i mængder på 200-1000 mg/dag. Patentkrav : Analogifremgangsmåde til fremstilling af terpenophenoler med den almene formel OH Ά, Br hvor R betegner: (2) 5-camphyl < (5)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1614274 | 1974-04-11 | ||
| GB16142/74A GB1510302A (en) | 1974-04-11 | 1974-04-11 | Terpenophenols |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK154075A DK154075A (da) | 1975-10-12 |
| DK142170B true DK142170B (da) | 1980-09-15 |
| DK142170C DK142170C (da) | 1981-02-09 |
Family
ID=10071943
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK154175AA DK142358B (da) | 1974-04-11 | 1975-04-10 | Analogifremgangsmåde til fremstilling af terpenophenoler. |
| DK154075AA DK142170B (da) | 1974-04-11 | 1975-04-10 | Analogifremgangsmåde til fremstilling af terpenophenoler. |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK154175AA DK142358B (da) | 1974-04-11 | 1975-04-10 | Analogifremgangsmåde til fremstilling af terpenophenoler. |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4067899A (da) |
| JP (2) | JPS5830288B2 (da) |
| BE (1) | BE827797A (da) |
| CA (2) | CA1055529A (da) |
| CH (2) | CH593891A5 (da) |
| DE (1) | DE2515382A1 (da) |
| DK (2) | DK142358B (da) |
| FR (1) | FR2267093B1 (da) |
| GB (1) | GB1510302A (da) |
| IE (1) | IE40910B1 (da) |
| LU (2) | LU72250A1 (da) |
| NL (2) | NL7504369A (da) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4301306A (en) * | 1980-03-27 | 1981-11-17 | The B. F. Goodrich Company | Norbornenyl phenolic compounds |
| JPS59116242A (ja) * | 1982-12-22 | 1984-07-05 | Kao Corp | シクロヘキサノ−ル誘導体および香料組成物 |
| ATE25513T1 (de) * | 1983-05-24 | 1987-03-15 | Dow Chemical Co | Bis(norbornyl oder substituierte norbornyl)derivate eines phenols oder phenylamines, verfahren zu ihrer herstellung und sie enthaltende zusammenstellungen. |
| US5382713A (en) * | 1993-02-05 | 1995-01-17 | Shell Oil Company | Phenolic compounds |
| RU2406487C1 (ru) * | 2009-05-06 | 2010-12-20 | Учреждение Российской академии медицинских наук Научно-исследовательский институт фармакологии Сибирского отделения РАМН | Средство, обладающее ретинопротекторной активностью |
| KR20130141492A (ko) * | 2010-09-28 | 2013-12-26 | 프로메러스, 엘엘씨 | 노르보르난-베이스 pac 밸러스트 및 상기 pac를 포함하는 포지티브형 감광성 수지 조성물 |
| WO2013006098A2 (ru) * | 2011-07-06 | 2013-01-10 | Федеральное Государственное Бюджетное Учреждение Науки Институт Химии Коми Научного Центра Уральского Отделения Российской Академии Наук | Производные 2,6-диизоборнилфенола |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2289550A (en) * | 1940-08-07 | 1942-07-14 | American Cyanamid Co | Nitro bornyl phenols as insecticides |
| US2537647A (en) * | 1948-02-21 | 1951-01-09 | Firestone Tire & Rubber Co | Rearrangement of terpenyl aryl ethers |
| US3878254A (en) * | 1962-11-28 | 1975-04-15 | Marpha Societe A Responsibilit | 6-isoformyl-3,4-xylenol and a process for its preparation |
| FR1355165A (fr) | 1963-04-11 | 1964-03-13 | Wolfen Filmfab Veb | Procédé de préparation de phénols terpéniques et de leurs éthers, et produits obtenus |
| GB1306217A (da) * | 1969-07-04 | 1973-02-07 |
-
1974
- 1974-04-11 GB GB16142/74A patent/GB1510302A/en not_active Expired
-
1975
- 1975-04-01 FR FR7510168A patent/FR2267093B1/fr not_active Expired
- 1975-04-02 CH CH415475A patent/CH593891A5/xx not_active IP Right Cessation
- 1975-04-02 CH CH415575A patent/CH593221A5/xx not_active IP Right Cessation
- 1975-04-07 IE IE773/75A patent/IE40910B1/xx unknown
- 1975-04-09 DE DE19752515382 patent/DE2515382A1/de not_active Withdrawn
- 1975-04-09 LU LU72250A patent/LU72250A1/xx unknown
- 1975-04-09 US US05/566,364 patent/US4067899A/en not_active Expired - Lifetime
- 1975-04-09 LU LU72249A patent/LU72249A1/xx unknown
- 1975-04-10 DK DK154175AA patent/DK142358B/da not_active IP Right Cessation
- 1975-04-10 DK DK154075AA patent/DK142170B/da not_active IP Right Cessation
- 1975-04-10 BE BE155288A patent/BE827797A/xx not_active IP Right Cessation
- 1975-04-11 JP JP50043490A patent/JPS5830288B2/ja not_active Expired
- 1975-04-11 CA CA224,571A patent/CA1055529A/en not_active Expired
- 1975-04-11 JP JP50043491A patent/JPS5830289B2/ja not_active Expired
- 1975-04-11 NL NL7504369A patent/NL7504369A/xx not_active Application Discontinuation
- 1975-04-11 CA CA224,583A patent/CA1045164A/fr not_active Expired
- 1975-04-11 NL NL7504368A patent/NL7504368A/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| BE827797A (fr) | 1975-07-31 |
| CH593221A5 (da) | 1977-11-30 |
| FR2267093B1 (da) | 1980-02-22 |
| DK154075A (da) | 1975-10-12 |
| DE2515382A1 (de) | 1975-11-06 |
| CH593891A5 (da) | 1977-12-30 |
| IE40910L (en) | 1975-10-11 |
| LU72250A1 (da) | 1975-08-20 |
| DK154175A (da) | 1975-10-12 |
| JPS5830289B2 (ja) | 1983-06-28 |
| DK142170C (da) | 1981-02-09 |
| CA1055529A (en) | 1979-05-29 |
| DK142358B (da) | 1980-10-20 |
| NL7504369A (nl) | 1975-10-14 |
| NL7504368A (nl) | 1975-10-14 |
| CA1045164A (fr) | 1978-12-26 |
| IE40910B1 (en) | 1979-09-12 |
| LU72249A1 (da) | 1975-08-20 |
| US4067899A (en) | 1978-01-10 |
| JPS50151857A (da) | 1975-12-06 |
| DK142358C (da) | 1981-07-06 |
| GB1510302A (en) | 1978-05-10 |
| JPS51118753A (en) | 1976-10-18 |
| FR2267093A1 (da) | 1975-11-07 |
| JPS5830288B2 (ja) | 1983-06-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Roblin Jr et al. | Studies in Chemotherapy. VIII. Methionine and Purine Antagonists and their Relation to the Sulfonamides1 | |
| Kaminsky et al. | Quinoline antibacterial agents. Oxolinic acid and related compounds | |
| DE2110388C3 (de) | Verfahren zur Herstellung von 2-Methylen- und 2-Methyl- A3 - cephalosporinverbindungen und deren Sulfoxiden | |
| DK142170B (da) | Analogifremgangsmåde til fremstilling af terpenophenoler. | |
| Clark et al. | The fungicidal activity of substituted acetanilides and related compounds | |
| DE2647515A1 (de) | Neue cephalosporinderivate | |
| Dunn et al. | Orally active 7-phenylglycyl cephalosporins structure-activity studies related to cefatrizine (SK&F 60771) | |
| CS390391A3 (en) | ANTI-MICROBIALLY ACTIVE 6,7-DIHYDRO-5,8-DIMETHYL -9- FLUOR-1-OXO-1H,5H-BENZO-(ij)-QUINAZOLINE-2-CARBOXYLIC ACID AND DERIVATIVES THEREOF | |
| FR2543953A1 (fr) | Analogue de la mitomycine comportant un groupe disulfure, leur preparation et leur application pharmacologique | |
| Morimoto et al. | Semisynthetic. beta.-lactam antibiotics. 1. Acylation of 6-aminopenicillanic acid with activated derivatives of. alpha.-sulfophenylacetic acid | |
| US3101377A (en) | Sulfone derivatives of mercaptohaloethylene | |
| Josey et al. | The Synthesis of N-Benzylthieno [3, 2-b] pyrrole1 | |
| US3171778A (en) | Biologically active applications of hexachloro-trithiane-tetroxide and trimethyl-tritiane-dioxide | |
| US3873591A (en) | Halo-substituted cyanomethyl benzenesulfonates | |
| JPH03287558A (ja) | 酵素阻害剤 | |
| US3767645A (en) | Acylthioacetyl penicillins | |
| CN114773389B (zh) | 具有抑菌活性的噁二唑杂环取代的季鏻盐及其制备方法和应用 | |
| US4060527A (en) | Pyrido[2,3-c]-acridine-1-hydroxy-2-carboxylic acid derivatives | |
| CH645905A5 (de) | Cephalosporinderivate, verfahren fuer ihre herstellung und antibakteriell wirkende zusammensetzungen, die solche verbindungen enthalten. | |
| CH593924A5 (en) | Cephalosporin carbamates - from alcohols and isocyanates | |
| SU1512480A3 (ru) | Способ получени производных гомопропаргиламина | |
| US2971962A (en) | Method of making the lactone of 2-hydroxybiphenyl-2'-carboxylic acid | |
| SU1301301A3 (ru) | Гербицидное средство | |
| US3445484A (en) | Organic phosphorus compounds | |
| Gilman et al. | Orientation in the Furan Nucleus. XII. 3-Methyl-4-furoic Acid and Some of its Derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed | ||
| PBP | Patent lapsed |