NO762960L - - Google Patents
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- Publication number
- NO762960L NO762960L NO762960A NO762960A NO762960L NO 762960 L NO762960 L NO 762960L NO 762960 A NO762960 A NO 762960A NO 762960 A NO762960 A NO 762960A NO 762960 L NO762960 L NO 762960L
- Authority
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- Norway
- Prior art keywords
- trans
- acid
- formula
- methylene
- group
- Prior art date
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- 239000002253 acid Substances 0.000 claims description 81
- 150000001875 compounds Chemical class 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- -1 1-heptyl Chemical group 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000000572 bronchospasmolytic effect Effects 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003180 prostaglandins Chemical group 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 230000017105 transposition Effects 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 230000002997 prostaglandinlike Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- OEBIHOVSAMBXIB-SJKOYZFVSA-N selitrectinib Chemical compound C[C@@H]1CCC2=NC=C(F)C=C2[C@H]2CCCN2C2=NC3=C(C=NN3C=C2)C(=O)N1 OEBIHOVSAMBXIB-SJKOYZFVSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical class C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 230000003191 uterotonic effect Effects 0.000 description 1
- 229940030508 uterotonics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (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)
Description
TITTEL : Fremgangsmåte for fremstilling av nye organiske forbindelser. TITLE: Process for the production of new organic compounds.
Foreliggende oppfinnelse vedrører en fremgangsmåte for fremstilling av nye organiske forbindelser med formel I The present invention relates to a method for the production of new organic compounds with formula I
hvori in which
A betyr en gruppe med formel Al til A7 eller et speilbilde av en gruppe med formel Al til A6, A means a group of formula Al to A7 or a mirror image of a group of formula Al to A6,
B • står for -CH2~CH2- eller (cis)-CH=CH,B • stands for -CH2~CH2- or (cis)-CH=CH,
D står for -CH2-CH2- eller (trans)- CH=CH,D stands for -CH2-CH2- or (trans)- CH=CH,
betyr alkyl med 1-10 karbonatomer eller en gruppe med means alkyl with 1-10 carbon atoms or a group with
formel IIformula II
hvori in which
Z står for alkylen med 1-5 karbonatomer,Z stands for the alkylene with 1-5 carbon atoms,
X står for -CH2- eller -0- ogX stands for -CH2- or -0- and
R^, R[- og Rg uavhengig av hverandre står for hydrogen, halogen R^, R[- and Rg independently of each other stand for hydrogen, halogen
med et atomtall fra 9 til 35 eller for trifluormetyl, with an atomic number from 9 to 35 or for trifluoromethyl,
R2betyr hydrogen eller alkyl med 1-7 karbonatomer, ogR2 means hydrogen or alkyl with 1-7 carbon atoms, and
R^betyr hydrogen, alkyl med 1-10 karbonatomer, med fenylmono- eller disubstituert alkyl med 1-10 karbonatomer eller ved bifenyl mono- eller disubstituert alkyl med 1-10 karbonatomer, med den betingelse at hvis, R^ means hydrogen, alkyl with 1-10 carbon atoms, with phenyl mono- or disubstituted alkyl with 1-10 carbon atoms or with biphenyl mono- or disubstituted alkyl with 1-10 carbon atoms, with the condition that if,
B står for (cis)-CH=CHogB stands for (cis)-CH=CHog
D står for (trans)-CH=CH,D stands for (trans)-CH=CH,
R^betyr en gruppe med formel IIIR₂ represents a group of formula III
hvori R 7 og Rg uavhengig av hverandre står for hydrogen eller alkyl med 1-4 karbonatomer, in which R 7 and Rg independently of each other stand for hydrogen or alkyl with 1-4 carbon atoms,
R^betyr hydrogen,R^ means hydrogen,
R^betyr hydrogen, alkyl med 1-8 karbonatomer eller med fenylmonosubstituert alkyl med 1-6 karbonatomer, R^ means hydrogen, alkyl with 1-8 carbon atoms or with phenyl monosubstituted alkyl with 1-6 carbon atoms,
så betyrso means
A en gruppe med formel A5 til A7 eller et speilbilde av en A a group with formula A5 to A7 or a mirror image of one
gruppe med formel A5 eller A6, og deres rasemater. group with formula A5 or A6, and their racemate.
Forbindelsene med formel I kan foreligge i optisk aktiv ellerThe compounds of formula I can be present in optically active or
i rasemisk form. De forbindelser med formel I som inneholder en karboksyl gruppe i 1-stillingen kan foreligge såvel i fri form som også i saltform. Fra de sistnevnte forbindelser i fri form lar salter seg utvinne og omvendt på i og for seg kjent måte. Således danner de salter.med baser, f.eks. natriumsaltet. in racemic form. The compounds of formula I which contain a carboxyl group in the 1-position can be present both in free form and also in salt form. From the latter compounds in free form, salts can be extracted and vice versa in a manner known per se. Thus they form salts with bases, e.g. the sodium salt.
Substituentene på cyklopropanringen står i cis- eller i trans-s.ti.llingen og foretrukket i trans-stilling til hverandre. The substituents on the cyclopropane ring are in the cis or trans position and preferably in the trans position to each other.
A betyr foretrukket en gruppe A2, A3 eller A4, foretrukketA preferably means a group A2, A3 or A4, preferably
A3 eller A4, spesieltA4. R^betyr foretrukket alkyl. StårA3 or A4, especially A4. R 2 preferably means alkyl. Stands
R^for alkyl er denne foretrukket rettkjedet og betyr f.eks. 1-heptyl eller 1-pentyl, eller er "forgrenet i a-stillingen, d.v.s. ved karbonatomet i 16-stil1 ingen av prostaglandin-skjellettet. Hvis karbonatomet i 16-stillingen er sekundært, betyr R^f.eks. 2-heksyl eller 5-nonyl og, hvis det ytterligere er asymmetrisk substituert, som ,i- 2-heksyl, er konfigurasjonen på karbonatomene i 15- og 16-stil1 ingen foretrukket identisk med konfigurasjonen i(.15S, 16R)-16-metyl-PGE2 • Hvis karbonatomet i 16-stillingen er tertiært, er to av alkylsubstituentene foretrukket identiske, som f.eks..i 2-metyl-2-heksyl. Z betyr foretrukket alkylen med 1-3 karbonatomer, spesielt metylen eller isopropyliden. X står foretrukket for -0-, halogen står foretrukket for fluor eller klor. En eller spesielt to av restene R^, R^og Rg betyr foretrukket hydrogen og den annen henhv. R^ for alkyl, this is preferably straight chain and means e.g. 1-heptyl or 1-pentyl, or is "branched in the a-position, i.e. at the carbon atom in the 16-style1 none of the prostaglandin skeleton. If the carbon atom in the 16-position is secondary, R^ means, e.g., 2-hexyl or 5-nonyl and, if further asymmetrically substituted, such as ,i- 2-hexyl, the configuration of the carbon atoms in the 15- and 16-style1 none is preferably identical to the configuration in (.15S, 16R)-16-methyl-PGE2 • If the carbon atom in the 16-position is tertiary, two of the alkyl substituents are preferably identical, as for example in 2-methyl-2-hexyl. Z preferably means the alkylene with 1-3 carbon atoms, especially methylene or isopropylidene. X preferably stands for -0-, halogen preferably stands for fluorine or chlorine. One or especially two of the radicals R^, R^ and Rg preferably means hydrogen and the other respectively
de andre står for foretrukket-i meta- eller para-stil1 ing.the others stand for preferred-in meta- or para-style1 ing.
To av restene R^, Rj. og Rg står foretrukket for hydrogen,Two of the residues R^, Rj. and Rg preferably stands for hydrogen,
den tredje rest står foretrukket for fluor i p-stilling eller trif lubrmetyl i m—still ing.-. R^ betyr foretrukket hydrogen. Står R^for alkyl betyr dette foretrukket metyl.. Står R^for alkyl med mer enn 2 karbonatomer er dette foretrukket rettkjedet. R2betyr foretrukket hydrogen eller usubstituert alkyl. Står R^for substituert alkyl inneholder dette foretrukket 1-4, spesielt 1 karbonatom og er foretrukket disubstituert med fenyl, spesielt på det samme karbonatom, spesielt på endekarbonatomet eller monosubstituert med bifenyl. R^ betyr f.eks. benzyl, difenylmetyl eller bifenyl-metyl. Foreligger forbindelsene med formel I i optisk aktiv form står 15-OH-gruppen foretrukket i den samme konfigurasjon som i naturlig PGE2, d.v.s. i oc-konfigurasjon. A står for en gruppe Al til A6 foretrukket et speilbilde av en gruppe Al til A6. the third residue preferably stands for fluorine in the p-position or triflubrmethyl in the m-position. R 1 preferably means hydrogen. If R^ stands for alkyl, this preferably means methyl. If R^ stands for alkyl with more than 2 carbon atoms, this is preferably straight chain. R2 preferably means hydrogen or unsubstituted alkyl. If R^ stands for substituted alkyl, this preferably contains 1-4, especially 1 carbon atom and is preferably disubstituted with phenyl, especially on the same carbon atom, especially on the terminal carbon atom or monosubstituted with biphenyl. R^ means e.g. benzyl, diphenylmethyl or biphenylmethyl. If the compounds of formula I are present in optically active form, the 15-OH group is preferably in the same configuration as in natural PGE2, i.e. in oc configuration. A stands for a group Al to A6, preferably a mirror image of a group Al to A6.
Det særegne ved fremgangsmåten i henhold til oppfinnelsenThe peculiarity of the method according to the invention
er at beskyttelsesgruppene avspaltes fra en forbindelse med formel IV. is that the protective groups are removed from a compound of formula IV.
hvori in which
A"<*>"har den ovenfor fon A angitte betydning eller står for en gruppe mee formel A8 eller A9, A"<*>" has the meaning given above for A or stands for a group with formula A8 or A9,
hvori R., betyr en syreømfintlig beskyttelsesgruppe eller står- for et sp.eilbilde av en gruppe med formel A8 eller A9, in which R. means an acid-sensitive protecting group or stands for a specific form of a group of formula A8 or A9,
B, D, R^og R2har den ovennevnte betydning,B, D, R^ and R 2 have the above meaning,
Rg har den ovennevnte for R^ angitte betydning eller betyr Rg has the meaning or means given above for R^
en syreømfin bl ig beskyttelsesgruppe, ogan acid-sensitive bl ig protecting group, and
R.nbetyr hydrogen eller en syreømfintlig beskyttelsesgruppe, R.n represents hydrogen or an acid-sensitive protecting group,
lu -vlu -v
med den betingelse at minst en syreømfintlig beskyttelsesgruppe foreligger, with the condition that at least one acid-sensitive protecting group is present,
eller fra et rasemat av en•forbindelse med formel IV. or from a race food of a compound of formula IV.
Fremgangsmåten i henhold til oppfinnelsen utgjør enThe method according to the invention constitutes a
avspalting av prostaglandin-beskyttelsesgruppe. Den kan gjennomføres analogt med kjente metoderEksempler på egnede besky ttel sesgrupper er tetrahydropyran-2-yl- og ter t-rbutyl-dimetylsilyl-gruppen. Eksempler på egnede sure reaksjonsmedier er følgende blandinger: cleavage of prostaglandin protecting group. It can be carried out analogously to known methods. Examples of suitable protecting groups are the tetrahydropyran-2-yl and tert-butyl-dimethylsilyl groups. Examples of suitable acidic reaction media are the following mixtures:
Eddiksyre/tetrahydrofuran, saltsyre/aceton, saltsyre/metanol og svovel syre/metanol. Om ønsket kan man arbeide i nærvær av vann. Temperaturen utgjør omtrent -10 til *50°C, foretrukket omtrent' +10 til +30°C. Forbindelsene med formel IV kan f.eks. erholdes ved at man analogt med kjente metoder, under Wittig-betingelser omsetter en forbindelse med formel V Acetic acid/tetrahydrofuran, hydrochloric acid/acetone, hydrochloric acid/methanol and sulfuric acid/methanol. If desired, you can work in the presence of water. The temperature is approximately -10 to *50°C, preferably approximately +10 to +30°C. The compounds of formula IV can e.g. is obtained by analogously to known methods, under Wittig conditions reacting a compound of formula V
hvori in which
R^, R^, R^q og D har den ovennevnte betydning og E betyr en gruppe med formel El til E3 R^, R^, R^q and D have the above meaning and E means a group of formula E1 to E3
hvori in which
R12betyr'hydrogen eller en syreømfintlig beskyttelsesgruppe, R12 means'hydrogen or an acid-sensitive protecting group,
elleror
betyr et speilbilde av en gruppe El til E3, means a mirror image of a group E1 to E3,
med en forbindelse med formel VI,with a compound of formula VI,
hvori Rg har den ovennevnte betydning og om nødvendig deretter i de således erholdte forbindelser med formel VII wherein Rg has the above-mentioned meaning and, if necessary, subsequently in the thus obtained compounds of formula VII
hvori in which
D, D^, R^, Rg og R^q har den ovennevnte betydning og F står for en gruppe med formel Fl .til F3 D, D^, R^, Rg and R^q have the above meaning and F stands for a group of formula Fl .to F3
hvori R.p har den ovennevnte betydning, eller står for et speilbilde av en gruppe Fl til F3 gjennomfører- en éi ler flere av de følgende omsetninger: a) oksydasjon av en gruppe Fl til en gruppe Al; b) oksydasjon av en gruppe F2 til en gruppe av A2 og om ønsket påfølgende isomerisering av den således erholdte gruppe A2 under alkaliske betingelser til en gruppe A7j c) oksydasjon av en gruppe F3 til en.gruppe A4 henh<y>. A9 og om ønsket etterfølgende reduksjon med natriumborhydrid ca) av en således erholdt gruppe A4 til gruppene A3 og A5 eller cb) av en således erholdt gruppe A9 til de to grupper A8 med 9-hydroksyl i a- henhv. |3-s till ingen og etterfølgende kromatografisk separering av de dannede forbindelser med 9-hydroksyl i oc-stillingen fra de dannede forbindelser med 9-hydroksyl i B-stillingen; d) oksydasjon av en gruppe F3, hvori R.^betyr hydrogen,, til en gruppe A6 og etterfølgende separering av de dannede forbindelser, som inneholder en gruppe A6, fra eventuelt dannede forbindelser som inneholder en gruppe A4; e) katalytisk hydrogenering av en forbindelse med formel VII til en forbindelse hvori 5,6-dobbeltbindingen er mettet, in which R.p has the above meaning, or stands for a mirror image of a group Fl to F3 carrying out several of the following reactions: a) oxidation of a group Fl to a group Al; b) oxidation of a group F2 to a group of A2 and, if desired, subsequent isomerization of the thus obtained group A2 under alkaline conditions to a group A7j c) oxidation of a group F3 to a group A4 henh<y>. A9 and, if desired, subsequent reduction with sodium borohydride ca) of a thus obtained group A4 to groups A3 and A5 or cb) of a thus obtained group A9 to the two groups A8 with 9-hydroxyl in a- respectively. |3-s to none and subsequent chromatographic separation of the formed compounds with 9-hydroxyl in the oc position from the formed compounds with 9-hydroxyl in the B position; d) oxidation of a group F 3 , in which R 1 is hydrogen, to a group A 6 and subsequent separation of the compounds formed, which contain a group A 6 , from any compounds formed which contain a group A 4 ; e) catalytic hydrogenation of a compound of formula VII to a compound in which the 5,6-double bond is saturated,
d.v.s. B står for -CH2-CH2, og/elleri.e. B stands for -CH2-CH2, and/or
f) ' beskyttelse av foreliggende hydroksy- og/eller karboksyl-grupper med en syreømfintlig beskyttelsesgruppe. f) 'protection of present hydroxy and/or carboxyl groups with an acid-sensitive protecting group.
Trinnene a) til f) kan også gjennomføres med forbindelser med formel VII, hvori F betyr et speilbilde av en gruppe Fl til F3, for fremstilling av de tilsvarende forbindelser med formel IV. Steps a) to f) can also be carried out with compounds of formula VII, in which F means a mirror image of a group Fl to F3, to prepare the corresponding compounds of formula IV.
For fremstilling av forbindelsene med formel IV i optiskFor the preparation of the compounds of formula IV in optical
aktiv form kan man gå ut fra optisk aktive forbindelser med formel V. For fremstilling av forbindelsene med formel IV active form, one can start from optically active compounds of formula V. For the preparation of the compounds of formula IV
i rasemisk form kan man gå ut fra forbindelser med formel IVin racemic form, one can start from compounds of formula IV
i rasemisk form.in racemic form.
Trinnene a) til f) kan gjennomføres analogt med kjenteSteps a) to f) can be carried out analogously to known ones
metoder. Man arbeider vanlig under milde betingelser. F.eks.methods. One usually works under mild conditions. E.g.
kan trinn e) gjennomføres i nærvær av palladium ved en temperatur på omtrent -40°C til -10°C for den selektive hydrogenering av 5,6-dobbeltbindingen i forbindelser med formel VII, som ennå inneholder en 13,14-dobbeltbinding. step e) can be carried out in the presence of palladium at a temperature of about -40°C to -10°C for the selective hydrogenation of the 5,6-double bond in compounds of formula VII, which still contain a 13,14-double bond.
I den utstrekning fremstillingen av de nødvendige utgangs-materialer ikke er beskrevet er disse kj:ente eller kan fremstilles og renses anlogt med i og for seg kjente metoder henhv. analogt med de her, f.eks. i eksemplene beskrevne eller anlogt med i og for seg kjente metoder. To the extent that the production of the necessary starting materials is not described, these are known or can be produced and purified appropriately using methods known in and of themselves or analogous to those here, e.g. in the examples described or applied with per se known methods.
Forbindelsene med formel I i optisk aktiv eller rasemisk form ogoevetituelt deres farmakologisk tålbare salter, i det følgende kort som substanser fremstilt i henhold til oppfinnelsen, fremviser interessante farmakodynamiske virkninger ved dyreforsøk og de kan følgelig anvendes som legemiddel. The compounds of formula I in optically active or racemic form and, alternatively, their pharmacologically tolerable salts, hereinafter briefly as substances produced according to the invention, exhibit interesting pharmacodynamic effects in animal experiments and they can consequently be used as medicine.
Spesielt viser de prostaglandin-lignende virkninger. Noen av disse virkninger er en uterus-stimulerende virkning, en bronkospasmolytisk virkning, en inhibering av mavesekresjonen, en senking av det artérielle blodtrykk, såvel som en inhibering av blodplateaggregasjonen. In particular, they show prostaglandin-like effects. Some of these effects are a uterine stimulating effect, a bronchospasmolytic effect, an inhibition of gastric secretion, a lowering of arterial blood pressure, as well as an inhibition of platelet aggregation.
På grunn av disse virkninger er de egnet for anvendelse som uterotonika, bronkospasmolytika, mavesyresekresjonshemmere, antihypertensiva og blodplateaggregasjonshemmere. Because of these effects, they are suitable for use as uterotonics, bronchospasmolytics, gastric acid secretion inhibitors, antihypertensives and platelet aggregation inhibitors.
Forbindelsen (lloc,13E, 15S, 16R)-11,15-dihydroksy-l6-metyl-9-okso-2,3-(-)-tran.s-metylen-prost-13-ensyre og dens fysiologisk -tålbare salter fremviser'en spesielt interessant bronkospasmolytisk virkning. Legemidler som inneholder en substans fremstilt i henhold til oppfinnelsen, f.eks. en løsning, en tablett eller en nebulisator kan fremstilles etter kjente metoder, under anvendelse av vanlige hjelpe- The compound (1loc,13E,15S,16R)-11,15-dihydroxy-16-methyl-9-oxo-2,3-(-)-tran.s-methylene-prost-13-enoic acid and its physiologically tolerable salts exhibits a particularly interesting bronchospasmolytic effect. Medicines containing a substance produced according to the invention, e.g. a solution, a tablet or a nebulizer can be prepared according to known methods, using common auxiliary
og bærer stoff er. Substans.ene kan tilføres alene eller i passende preparatform. and carries substance is. The substances can be added alone or in a suitable preparation form.
I de etterfølgende eksempler, som illustrerer oppfinnelsen nærmere.;, er alle temper aturangi vel ser i °C og er ukorrigert. In the following examples, which illustrate the invention in more detail, all temperatures are in °C and are uncorrected.
IR vedrører de karakteristiske bånd ved infrarød-spektrumIR relates to the characteristic bands of the infrared spectrum
(i metylenkloridløsning). Betegnelsen av forbindelsene er basert på natTuerlig prostansyre, med den 5-leddede ring til vénstre og de to sidekjeder til høyre.Forstavelsen "epi" betyr at det angitte karbonatom har konfigurasjon motsatt konfigurasjonen av prostansyre ved dette karbonatom. "(+)" eller "(-)-trans-metylen" vedrører den som utgangsprodukt anvendte-(+)- eller (in methylene chloride solution). The designation of the compounds is based on natural prostanic acid, with the 5-membered ring on the left and the two side chains on the right. The prefix "epi" means that the specified carbon atom has a configuration opposite to the configuration of prostanic acid at this carbon atom. "(+)" or "(-)-trans-methylene" refers to the (+)- or used as starting product
(-)-trans-2-(2'-brornetyl)cykloprop-1-yl-karboksyl syre henholdsvis (-)-trans-2-(2'-bromomethyl)cycloprop-1-yl-carboxylic acid, respectively
dens ester. its ester.
Eksempel 1: lia', 13E, 15S, 16R -11, 15-dihydroksy-16-metyl-9- Example 1: 11a', 13E, 15S, 16R -11, 15-dihydroxy-16-methyl-9-
dkso-2', 3-(-)*»trans-metylenprosta-13-ensyre.dkso-2', 3-(-)*» trans-methyleneprosta-13-enoic acid.
400 mg lia, 13E, 15S; 16R -11-, 15-bis tetrahydropyran-2'-yloksy-16-metyl-9-okso-2,3-(-)-trans-metylen-prosta-13-ensyre oppløses i 18 ml av en 1:1:1 blanding av eddiksyre/tetrahydrofpran/vann. Etter 36 timer ved romtemperatur inndampes løsningen og resten kromatograferes på silikagel med kloroform/1% metanol. Man erholder den i overskriften nevnte forbindelse (IR 3650, 3500-3400, 1745-1740, 1700-1690 cm<-1>). 400 mg lia, 13E, 15S; 16R -11-, 15-bis tetrahydropyran-2'-yloxy-16-methyl-9-oxo-2,3-(-)-trans-methylene-prosta-13-enoic acid is dissolved in 18 ml of a 1:1: 1 mixture of acetic acid/tetrahydrofuran/water. After 36 hours at room temperature, the solution is evaporated and the residue is chromatographed on silica gel with chloroform/1% methanol. The compound mentioned in the title is obtained (IR 3650, 3500-3400, 1745-1740, 1700-1690 cm<-1>).
Utgangsproduktet erholdes på følgende måte:The starting product is obtained in the following way:
a) 600 mg natriumborhydrid suspenderes i 6 ml absolutt dimetylsulfoksyd og suspensjonen holdes under nitrogen i 55 minutter a) 600 mg of sodium borohydride are suspended in 6 ml of absolute dimethyl sulphoxide and the suspension is kept under nitrogen for 55 minutes
ved 75°C. Etter avkjøling tildryppes 4,5 ml av denne løsning langsomt til en på forhånd fremstilt løsning av 4,08 g tfifenyl-fosfoniumsalt av (-)-trans-2-(2'-brornetyl)cykloprop-l-ylkarboksyl-syre i 10 ml dimetylsul foksyd.og omrøres under nitrogen i 45 at 75°C. After cooling, 4.5 ml of this solution is slowly added dropwise to a previously prepared solution of 4.08 g of the triphenylphosphonium salt of (-)-trans-2-(2'-bromomethyl)cycloprop-1-ylcarboxylic acid in 10 ml dimethylsulfoxide.and stirred under nitrogen for 45
.minutter. 8 ml av den erholdte ylid-løsning tilsettes langsomt.minutes. 8 ml of the ylide solution obtained is added slowly
til en løsning av 2,0 g 2|3-(4' R-metyl-3 1 S-tetrahydropyran-2-yloksyTtrans-l'-oktenyl)-5a-hydroksy-3a-tetrahydropyran-21 - yloksycyklopent-loc-yitéddiksyre-^- -laktal i 6 ml absolutt tetra-hydrofuran og 6 ml. dimetylsulfoksyd. Reaksjonsblandingen holdes i 60 minutter ved 50°C. Etter tilsetning av ytterligere 8 ml av yl idiøsningen holdes temperaturen nok en gang i 1 time ved 50°C. to a solution of 2.0 g of 2|3-(4'R-methyl-3 1S-tetrahydropyran-2-yloxyTtrans-1'-octenyl)-5a-hydroxy-3a-tetrahydropyran-21-yloxycyclopent-loc-yl acetic acid -^- -lactal in 6 ml of absolute tetra-hydrofuran and 6 ml. dimethyl sulfoxide. The reaction mixture is kept for 60 minutes at 50°C. After adding a further 8 ml of the aqueous solution, the temperature is maintained once more for 1 hour at 50°C.
Den avkjølte reaksjonsblanding uthelles på.100 g is, den vandige fase innstilles til pH 3-4, ekstraheres 3 ganger med metylenklorid og kromatograferes på silikagel med kloroform/2% metanol, hvorved (5Z, 9a, lia, 13E, . 15.S, 16R)-11, 15-bis (tetrahydropyran-2 1 -yloksy)-^-9-hydroksy^l6-metyl-2 , 3-(-) -trans-metylenprosta-5 ,13-diensyre erholdes (IR 3600, 3550, 1730-1690 cm"<1>). b) l,6 g av (5Z, 9a, lia, 13E, 15S, 16R)-11,15-bis(tetrahydropyran-2'-yloksy)-9-hydroksy-16-mety1-2^3-(-)-trans-metylenprosta-5,13-diensyre i 150 ml aceton omsettes v ed -15°C etter Jones under anvendelse av avmålte mengder av en blanding av 13,34 g krom(VI) trioksyd, 10,7 ml svovelsyre og 35 ml vann, som tilsettes dråpevis. Etter 25 minutter tilsettes metanol og etter ytterligere 10 minutter uthelles blandingen på 300 ml isblandet vann og ektraheres fibere ganger med metylenklorid. Forbindelsen (5Z, lia,13E, 15S, 16R)-11, 15-bis(tetrahydropyran-2'-yloksy)-16-metyl-9-oksy-2,3-(-0-trans-metylenprosta-5 , 13-diensyre érholdes (IR: 3500, 1740-1730, 1690 em<-1>). c) 460 m<3 av (5Z, lia, 13E, 15S, 16R)-11,15-bis (tetrahydropyran-2«-yloksy)-16-metyl-9-okso-2,3-(-)-trans-metyleriprosta—5,13-diensyre i 40 ml absolutt metanol hydrogeneres i 3 timer ved -15°C til -10°C i nærvær av 100 mg palladium/kull, hvorved (lia, 13E, 15S, 16R)-11,15-bis(tetrahydropyran-2<1->yloksy)-16-metyl-9-okso-2,3-(-)-trans-metylen-prost-13-ensyre erholdes. The cooled reaction mixture is poured onto 100 g of ice, the aqueous phase is adjusted to pH 3-4, extracted 3 times with methylene chloride and chromatographed on silica gel with chloroform/2% methanol, whereby (5Z, 9a, 11a, 13E, 15.S . 3550, 1730-1690 cm"<1>). b) 1.6 g of (5Z, 9a, 11a, 13E, 15S, 16R)-11,15-bis(tetrahydropyran-2'-yloxy)-9-hydroxy -16-methyl-2^3-(-)-trans-methyleneprosta-5,13-dienoic acid in 150 ml of acetone is reacted at -15°C according to Jones using measured amounts of a mixture of 13.34 g of chromium ( VI) trioxide, 10.7 ml of sulfuric acid and 35 ml of water, which are added dropwise. After 25 minutes methanol is added and after a further 10 minutes the mixture is poured into 300 ml of ice water and extracted several times with methylene chloride. The compound (5Z, 11a, 13E, 15S,16R)-11,15-bis(tetrahydropyran-2'-yloxy)-16-methyl-9-oxy-2,3-(-0-trans-methyleneprosta-5,13-die n acid is retained (IR: 3500, 1740-1730, 1690 em<-1>). c) 460 m<3 of (5Z, 11a, 13E, 15S, 16R)-11,15-bis(tetrahydropyran-2'-yloxy)-16-methyl-9-oxo-2,3-(-)-trans -methyleriprosta—5,13-dienoic acid in 40 ml absolute methanol is hydrogenated for 3 hours at -15°C to -10°C in the presence of 100 mg palladium/charcoal, whereby (lia, 13E, 15S, 16R)-11,15 -bis(tetrahydropyran-2<1->yloxy)-16-methyl-9-oxo-2,3-(-)-trans-methylene-prost-13-enoic acid is obtained.
Analogt med eks. 1 erholdes følgende forbindelser med formel .1Analogous to e.g. 1, the following compounds with formula .1 are obtained
ved å gå ut fra de tilsvarende 15-tetrahydrbpyran-2-yletere med formel IV, hvori Rg har betydningen av R^, eller hvis slutt-produktet inneholder en 11-hydroksygruppe, ved å gå ut fra de tilsvarende 11,15-bis(tetrahydropyran-2-yl)etére med formel IV, hvori Rg har betydningen av R^. starting from the corresponding 15-tetrahydrbpyran-2-yl ethers of formula IV, in which Rg has the meaning of R^, or if the end product contains an 11-hydroxy group, starting from the corresponding 11,15-bis( tetrahydropyran-2-yl)ether of formula IV, in which Rg has the meaning of R^.
Eksempel 2: (5Z, 9a, lia, 13E, 15R)-15-metyl-9, 11, 15-trihydrbksy-2,3-(-)-trans-metylen-prosta-5, 13-diensyremetylester IR: 3660-3400, 1710-1700 cm"<1>Example 2: (5Z, 9a, 11a, 13E, 15R)-15-methyl-9, 11, 15-trihydroxy-2,3-(-)-trans-methylene-prosta-5, 13-dienoic acid methyl ester IR: 3660- 3400, 1710-1700 cm"<1>
Eksempel; 3: (5Z, 9a, lia, 13E, 15S)-15-metyl-9, 11, 15-trihydroksy-2,3-(-)-trans-metylen-prosta-5, 13-diensyrenretyl ester Smeltepunkt 16- 11- C Example; 3: (5Z, 9a, 1a, 13E, 15S)-15-methyl-9, 11, 15-trihydroxy-2,3-(-)-trans-methylene-prosta-5, 13-diene acid retyl ester Melting point 16- 11 - C
Eksempel 4: (5Z, 9a, Ila, 13E, 15R)-15-metyl-9, 11, 15-trihydroksy-2,3-(+)-trans-metylen-prosta-5, 13-diensyremetylester IR: 3550, 1710 cm Example 4: (5Z, 9a, 11a, 13E, 15R)-15-methyl-9, 11, 15-trihydroxy-2,3-(+)-trans-methylene-prosta-5, 13-dienoic acid methyl ester IR: 3550, 1710 cm
Eksempel 5: (5Z, 9a, lia, 13E, 15S)-15-metyl-9, 11, 15-trihydroksy-2,3-(+)-trans-metylen-prosta-5, 13-diensyremetylester' Smeltepunkt 68-70°C Example 5: (5Z, 9a, 11a, 13E, 15S)-15-methyl-9, 11, 15-trihydroxy-2,3-(+)-trans-methylene-prosta-5, 13-dienoic acid methyl ester' Melting point 68- 70°C
Eksempel '6: (5Z, 9a, lia, 13E, 15S)-15-metyi-9, 11, 15-trihydroksy-2,3-(-)-trans-metylen-prostaT5, 13-diensyre"Example '6: (5Z, 9a, 11a, 13E, 15S)-15-methyl-9, 11, 15-trihydroxy-2,3-(-)-trans-methylene-prostaT5, 13-dienoic acid"
IR: 3500-3300, 1700 cm"<1>IR: 3500-3300, 1700 cm"<1>
Eksempel 7: (5Z*9a, lia, 13E, 15R)-15-metyl-9, 11, 15-trihydroksy-^Example 7: (5Z*9a, 11a, 13E, 15R)-15-methyl-9, 11, 15-trihydroxy-^
2, 3-( -) ^-trans-metyifcen-prosta-5 , 13-diensyre2, 3-( -) ^-trans-methylifcene-prosta-5, 13-dienoic acid
IR: 3500-3300, 1700 cm"<1>IR: 3500-3300, 1700 cm"<1>
Eksempel 8: (5Z, 9a, lia, 13E, 15R)-15-metyl-9, 11, 15-trihydroksy-2 , 3-(+ )-trans-metylen-prosta-5., 13-diensyre Example 8: (5Z, 9a, 11a, 13E, 15R)-15-methyl-9, 11, 15-trihydroxy-2, 3-(+ )-trans-methylene-prosta-5, 13-dienoic acid
IR: 3550-3300, 1720-1680 cm"<1>IR: 3550-3300, 1720-1680 cm"<1>
Eksempel 9: (5Z, 9a, lia, 13E, 15S)-15-metyl-9, 11, 15-trihydroksy-2, 3-( + ) -trans-mety3;en-prosta-5 , 13-diensyre Example 9: (5Z, 9a, 11a, 13E, 15S)-15-methyl-9, 11, 15-trihydroxy-2, 3-( + )-trans-methylene-prosta-5, 13-dienoic acid
IR: 3600-3300, 1720-1680 cm 1 IR: 3600-3300, 1720-1680 cm 1
Eksempel 10: (5Z, lia, 13E, 15R)-11, 15-dihydroksy-15-metyl-9-okso-2,3-(«)-trans-metylen-prosta-5, 13-diensyremetylester Example 10: (5Z, 11a, 13E, 15R)-11, 15-dihydroxy-15-methyl-9-oxo-2,3-(«)-trans-methylene-prosta-5, 13-dienoic acid methyl ester
IR: 3600, 1740-1710 cm"<1>IR: 3600, 1740-1710 cm"<1>
Eksempel 11: (5Z, 9a, 13E, 15R)-9, 15-dihydroksy-15-metyl-ll-okso-2,3-(-)-trans-metylen-prosta-5, 13-diensyre-metyl ester Example 11: (5Z, 9a, 13E, 15R)-9, 15-dihydroxy-15-methyl-11-oxo-2,3-(-)-trans-methylene-prosta-5, 13-dienoic acid methyl ester
IR: 3600, 1740-1710 cm IR: 3600, 1740-1710 cm
Eksempel 12: (5Z, lia, 13E, 15R)-11, 15-dihydroksy-15-metyl-9-okso-2,3-(+)-trans-metyelen-prosta-5, 13-diensyre-metyjlester Example 12: (5Z, 11a, 13E, 15R)-11, 15-dihydroxy-15-methyl-9-oxo-2,3-(+)-trans-methylene-prosta-5, 13-dienoic acid methyl ester
IR: 3600, 1740-1710 cm '' ■ IR: 3600, 1740-1710 cm '' ■
Eksempel 13: (5Z, 9a, 13E, 15R)-9,15-dihydroksy-15-metyl-ll-okso-2,3-(+)-trans-metylen-prosta-5, 13-diensyremetylester IR: 3600, 1740-1710 cm"<1>. Example 13: (5Z, 9a, 13E, 15R)-9,15-dihydroxy-15-methyl-11-oxo-2,3-(+)-trans-methylene-prosta-5, 13-dienoic acid methyl ester IR: 3600, 1740-1710 cm"<1>.
Eksempel 14: (5Z, lia, 13E, 15S)-11, 15-dihydroksy-15-metyl-9-okso-2,3-(-)-trans-metylen-prosta-5, 13/diensyremetylester Example 14: (5Z, 11a, 13E, 15S)-11, 15-dihydroxy-15-methyl-9-oxo-2,3-(-)-trans-methylene-prosta-5, 13/dienoic acid methyl ester
IR: 3600, 17.40-170© cm"<1>' IR: 3600, 17.40-170© cm"<1>'
Eksempel 15: (5Z, 9a, 13E, 15S)-9, 15-dihydroksy-15-metyl-ll-okso-2,3 Example 15: (5Z, 9a, 13E, 15S)-9, 15-dihydroxy-15-methyl-11-oxo-2,3
2, 3-(-)-trans-metylenrprosta-5 , 13-diensyremetylester2, 3-(-)-trans-methylene-prosta-5, 13-dienoic acid methyl ester
IR: 3600, 1740-1700 cm"<1>IR: 3600, 1740-1700 cm"<1>
Eksempel 16: (5Z, lia, 13E, 15S)-11,15-dihydroksyv*15-metyl-9-okso-2,3-( + )-trans-met<y>ie<n>-<p>rosta-5, 13-diensyremetylester Example 16: (5Z, 11a, 13E, 15S)-11,15-dihydroxyv*15-methyl-9-oxo-2,3-( + )-trans-met<y>ie<n>-<p>rosta -5, 13-dienoic acid methyl ester
IR: 3600, 1740-1700 cm"<1>IR: 3600, 1740-1700 cm"<1>
Eksempel 17: (5Z, 9a, 13E, 15S)-9,15-dihydroksy-15-metyl-ll-okso-2, 3-( + )-trans-mebji=a3-prosta-5 , 13-diensyremetylester Example 17: (5Z, 9a, 13E, 15S)-9,15-dihydroxy-15-methyl-11-oxo-2,3-( + )-trans-methyl=α3-prosta-5,13-dienoic acid methyl ester
IR: 3600, 1740-1700 cm"<1>IR: 3600, 1740-1700 cm"<1>
Eksempel 18: (5Z, lia, 13E, 15R)-11, 15-dihydroksy-15-metyl-9-okso-2,3-(-)-trans-metylen-prosta-5, 13-diensyre Example 18: (5Z, 11a, 13E, 15R)-11, 15-dihydroxy-15-methyl-9-oxo-2,3-(-)-trans-methylene-prosta-5, 13-dienoic acid
IR: 3600, 3400, 1735, 1695 cm<-1>IR: 3600, 3400, 1735, 1695 cm<-1>
Eksempel 19: (5Z, lia, 13E, 15R)-11, 15-dihydroksy-15-metyl-9-okso-2,3-(+)-trans-metylen-prosta-5, 13-diensyre Example 19: (5Z, 11a, 13E, 15R)-11, 15-dihydroxy-15-methyl-9-oxo-2,3-(+)-trans-methylene-prosta-5, 13-dienoic acid
IR: 3600, 3500-3400, 1735, 1695 cm"<1>IR: 3600, 3500-3400, 1735, 1695 cm"<1>
Eksempel 20: (5Z, 9a, 13E, 15R)-9, 15-dihydroksy-15-metyl-ll-okso-2,3-(-)-trans-metylen-prosta-5, 13-diensyre Example 20: (5Z, 9a, 13E, 15R)-9, 15-dihydroxy-15-methyl-11-oxo-2,3-(-)-trans-methylene-prosta-5, 13-dienoic acid
IR: 3600, 3500-3400, 1740-1730, 1700-1690 cm"<1>IR: 3600, 3500-3400, 1740-1730, 1700-1690 cm"<1>
Eksempel 21: (5Z, 9a, 13E, 15R)-9, 15-dihydroksy-15-.metyl-ll-okso-..2,J3-( + )-trans-metylen-prosta-5, 13-diensyre Example 21: (5Z, 9a, 13E, 15R)-9, 15-dihydroxy-15-.methyl-11-oxo-..2,J3-( + )-trans-methylene-prosta-5, 13-dienoic acid
IR: 3600, 3500-3400, 1740-1730, 1700-1690 cm"<1>IR: 3600, 3500-3400, 1740-1730, 1700-1690 cm"<1>
Eksempel 22: (5Z, lia, 13E, 15S)-11, 15-dihUdroksy-l'5-metyl-9-•kso-2,3-(-)-trans-metylen-prosta-5, 13-diensyre Example 22: (5Z,11a,13E,15S)-11,15-Dihydroxy-1'5-methyl-9-•xo-2,3-(-)-trans-methylene-prosta-5,13-dienoic acid
IR: 3600-3300, 1740-1760 cm"<1>IR: 3600-3300, 1740-1760 cm"<1>
Eksempel 23: (5Z, lia, 13E, 15S)-11, 15-dihydroksy-15-metyl-9 Example 23: (5Z, 11a, 13E, 15S)-11, 15-dihydroxy-15-methyl-9
okso-2,3-(+)-trans-metylen-prosta-5, 13-diensyreoxo-2,3-(+)-trans-methylene-prosta-5, 13-dienoic acid
IR: 3550, 3450, 1735, 1690 cm"<1>IR: 3550, 3450, 1735, 1690 cm"<1>
Eksempel 24: (5Z, 9a, 13E, 15S)-9, 15-dihydroksy-15-metyk-ll- Example 24: (5Z, 9a, 13E, 15S)-9, 15-dihydroxy-15-methyl-11-
okso-2,3-(-)-trans-metylen-prosta-5, 13-diensyreoxo-2,3-(-)-trans-methylene-prosta-5, 13-dienoic acid
IR: 3600, 3500-3400, 1740-1730, 1695 cm"<1>IR: 3600, 3500-3400, 1740-1730, 1695 cm"<1>
Eksempel 25: (5Z, 9a, 13E, 15S)-9, 15-dihydroksy-15-metyl-ll-okso-2,3-(+)-trans-metylen-prosta-5, 13-diensyre Example 25: (5Z, 9a, 13E, 15S)-9, 15-dihydroxy-15-methyl-11-oxo-2,3-(+)-trans-methylene-prosta-5, 13-dienoic acid
IR: 3600, 3500-3400, 1740-1730, 1700-1690. cm"1 IR: 3600, 3500-3400, 1740-1730, 1700-1690. cm"1
Eksempel 26: (5Z, 9a, lia, 15S)-16, 16-dimetyl-9, 11, 15-trihydroksy-2,3-(-)-trahs-metylen-prosta-5-ensyre IR: 3600, 3500, 1690 cm"<1>Example 26: (5Z, 9a, 11a, 15S)-16, 16-dimethyl-9, 11, 15-trihydroxy-2,3-(-)-trachmethylene-prosta-5-enoic acid IR: 3600, 3500, 1690 cm"<1>
Eksempel 27: (5Z, 9a, lia, 15S)-16, 16-dimetyl-9, 11, 15-trihydroksy-2,3-(+)-trans-metylen-prosta-5-ensyre IR: 3600, 3500-3400, 1700-1690 cm"<1>Example 27: (5Z, 9a, 11a, 15S)-16, 16-dimethyl-9, 11, 15-trihydroxy-2,3-(+)-trans-methylene-prosta-5-enoic acid IR: 3600, 3500- 3400, 1700-1690 cm"<1>
Eksempel -28: (5Z, lia, 15S)-11, 15-dihydroksy-16, 16-dimetyl-9-okso-2,3-(-)-trans-metylen-prosta-5-ensyre Example -28: (5Z, 11a, 15S)-11, 15-dihydroxy-16, 16-dimethyl-9-oxo-2,3-(-)-trans-methylene-prosta-5-enoic acid
IR: 3600, 3450,,1735, 1690 cm<-1>IR: 3600, 3450,,1735, 1690 cm<-1>
Eksempel 29: (5Z, lia, 15S)-11, 15-dihydroksy-16, 16-dimetyl-9-okso-2,3-(+)-trans-metylen-prosta-5-ensyre Example 29: (5Z, 11a, 15S)-11, 15-dihydroxy-16, 16-dimethyl-9-oxo-2,3-(+)-trans-methylene-prosta-5-enoic acid
IR: 3600, 3500-3400, 1740-1730, 1690 cm"<1>IR: 3600, 3500-3400, 1740-1730, 1690 cm"<1>
Eksempel 30: (5Z, 15S)-16, 16-dimetyl-15-hydroksy-9-okso-2,3-(-)-trans-metylen-prosta-5, 10-diensyre Example 30: (5Z, 15S)-16, 16-dimethyl-15-hydroxy-9-oxo-2,3-(-)-trans-methylene-prosta-5, 10-dienoic acid
IR: 3500,, 1730, 1690 cm<-1>IR: 3500, 1730, 1690 cm<-1>
Eksempel 31: (5Z, 15S)-16, 16-dimetyl-15-hydroksy-9-okso-2,3-(+)-trans-metylen-prosta-5, 10-diensyre Example 31: (5Z, 15S)-16, 16-dimethyl-15-hydroxy-9-oxo-2,3-(+)-trans-methylene-prosta-5, 10-dienoic acid
IR: 3600, 3500, 1735-1730, 1695-1690 cm<-1>IR: 3600, 3500, 1735-1730, 1695-1690 cm<-1>
Eksempel 32: (9a, lia, 13E, 15R)-16, 16-dimetyl-9, 11, 15-trihydroksy-2,3-(+)-trans-metylen-prosta-13-ensyre IR: 3600-3400, 1695 cm<-1>Example 32: (9a, 11a, 13E, 15R)-16, 16-dimethyl-9, 11, 15-trihydroxy-2,3-(+)-trans-methylene-prosta-13-enoic acid IR: 3600-3400, 1695 cm<-1>
Eksempel 33: (9a, lia, 13E, 15S)-16-n-butyl-9, 11, 15-trihydroksy-2,3-(-)-trans-metylen-prosta-13-ensyre Example 33: (9a, 11a, 13E, 15S)-16-n-butyl-9, 11, 15-trihydroxy-2,3-(-)-trans-methylene-prosta-13-enoic acid
IR: 3600, 3500-3400, :.1700-1690 cm"<1>' IR: 3600, 3500-3400, :.1700-1690 cm"<1>'
Eksempel 34: (9a, lia, 13E, 15S)-16-n-butyl-9, 11,- 15-trihydroksy-' Example 34: (9a,11a,13E,15S)-16-n-butyl-9,11,-15-trihydroxy-'
2,3-(+)-trans-metylen-prosta-13-ensyre2,3-(+)-trans-methylene-prosta-13-enoic acid
IR: -3600, 3500-3400, 1700-1690 cm<-1>IR: -3600, 3500-3400, 1700-1690 cm<-1>
Eksempel 35: (Ila, 13E, 15R)-11, 15-dihydroksy-16, 16-dimetyl-9-okso--2 , 3-(■ + ) - trans-metyl en-pros ta-13-ensyre Example 35: (11a, 13E, 15R)-11, 15-dihydroxy-16, 16-dimethyl-9-oxo--2, 3-(■ + )-trans-methyl en-prosta-13-enoic acid
IR: 3400, 1735, 1690 cm<-1>IR: 3400, 1735, 1690 cm<-1>
Eksempel 36: (lia, 13E, 15S)-16-n-butyl-ll, 15-di$ydroksy-9-okso-2,3-(-)-trans-metylen-prosta-13-ensyre Example 36: (11a,13E,15S)-16-n-butyl-11,15-dihydroxy-9-oxo-2,3-(-)-trans-methylene-prosta-13-enoic acid
IR: 3600, 3400, 1740-1730, 1690 cm"<1>IR: 3600, 3400, 1740-1730, 1690 cm"<1>
Eksempel 37: (lia, 13E, 15S)-16-n-butyl-ll, 15-dihydroksy-9-okso-2,3-(+)-trans-metylen-prosta-13-ensyre Example 37: (11a, 13E, 15S)-16-n-butyl-11,15-dihydroxy-9-oxo-2,3-(+)-trans-methylene-prosta-13-enoic acid
IR: 3600, 3500-3400, 1735, 1700-1690 cm"<1>IR: 3600, 3500-3400, 1735, 1700-1690 cm"<1>
Eksempel 38: (13E, 15R)-16, 16-dimetyl-15-hydroksy-9-okso-2,3-(+)-trans-metylen-prosta-10, 13-diensyre Example 38: (13E,15R)-16,16-dimethyl-15-hydroxy-9-oxo-2,3-(+)-trans-methylene-prosta-10,13-dienoic acid
IR: 3600, 1695 cm<-1>IR: 3600, 1695 cm<-1>
Eksempel 39: (13E, 15S)-16-n-buty3:-15-hydroksy-9-okso-2 , 3-(-) - Example 39: (13E,15S)-16-n-Buty3:-15-hydroxy-9-oxo-2,3-(-)-
trans-metylen-prosta-10, 13-diensyretrans-methylene-prosta-10, 13-dienoic acid
IR: 3600, 3500-3400, 1700-1690 cm<-1>IR: 3600, 3500-3400, 1700-1690 cm<-1>
Eksempel 40: (13E, 15S)-16-n-butyl-15-hydrok'syr49-cGks6-2 , 3-( +) - Example 40: (13E, 15S)-16-n-butyl-15-hydroxy acid 49-cGks6-2,3-(+)-
trans-metylen-prosta-10, 13-diensyretrans-methylene-prosta-10, 13-dienoic acid
IR: 3600, 1695 cm<-1>IR: 3600, 1695 cm<-1>
Eksempel 41: (9a, lia, 15R)-16, 16-dimetyl-9, 11, 15-trihydroksy-2,3-(+)-trans-metylen-prostansyre Example 41: (9a, 11a, 15R)-16, 16-dimethyl-9, 11, 15-trihydroxy-2,3-(+)-trans-methylene-prostanic acid
IR: 3600-3400, 1695 cm<-1>IR: 3600-3400, 1695 cm<-1>
Eksempel 42: (9a, ^Lla, 15R)-16, 16-dimetyl-9, 11, 15-trihydroksy-2,3-(-)-trans-metylen-prostansyre Example 42: (9a, ^Lla, 15R)-16, 16-dimethyl-9, 11, 15-trihydroxy-2,3-(-)-trans-methylene-prostanoic acid
IR: 3600, 3500-3400, 1700-1690 cm<-1>IR: 3600, 3500-3400, 1700-1690 cm<-1>
Eksempel 43: (9a, lia, 15R)-16-n-butyl-9', 11, 15-trihydroksy-2,3-(-)-trans-metylen-prostansyre l IR: 3600, 3500-3400, 1695 cm"<1>Example 43: (9a, 11a, 15R)-16-n-butyl-9', 11, 15-trihydroxy-2,3-(-)-trans-methylene-prostanic acid 1 IR: 3600, 3500-3400, 1695 cm "<1>
Eksempel 44: (9a, lia, 15R)-16-n-butyl-9', 11, 15-trihydroksy-2,3-(+)-trans-metylen-prostansyre Example 44: (9a, 11a, 15R)-16-n-butyl-9', 11, 15-trihydroxy-2,3-(+)-trans-methylene-prostanic acid
IR: 3600-3400'1695 cm<-1>IR: 3600-3400'1695 cm<-1>
Eksempel 45: (lia, 15S)-11, 15-dihydroksy-9-okso-2,3-(-)-trans-metyl en-pros tansyre- Example 45: (11a, 15S)-11, 15-dihydroxy-9-oxo-2,3-(-)-trans-methyl en-prostanic acid-
IR: 3600, 3400, 1735, 1690 cm<-1>IR: 3600, 3400, 1735, 1690 cm<-1>
Eksempel 46: (lia, 15S)-11, 15-dihydroksy-9-okso-2., 3-(,+ )-trans-metyl en-prostansyre Example 46: (11a, 15S)-11, 15-dihydroxy-9-oxo-2., 3-(,+ )-trans-methyl en-prostanoic acid
IR: 3600; 3400, 1740-1730, 1690 cm<-1>IR: 3600; 3400, 1740-1730, 1690 cm<-1>
Eksempel 47: (lia,. 15S)-11, 15-dihydroksy-16, 16-dimetyl-9-okso-2,3-(-)-trans-metylen-prostansyre Example 47: (11a,.15S)-11,15-dihydroxy-16,16-dimethyl-9-oxo-2,3-(-)-trans-methylene-prostanic acid
IR: 3600,. 3500-3400, 1735,1700-1690 cm<-1>IR: 3600,. 3500-3400, 1735,1700-1690 cm<-1>
Eksempel 48: (lia, 15R)-11, 15-dihydroksy-16, 16-dimetylr9-okso-2,3-(+)-trans-metylén^prostansyre Example 48: (11a, 15R)-11, 15-dihydroxy-16, 16-dimethyl R9-oxo-2,3-(+)-trans-methylene^prostanic acid
IR: 3600, 3500-3400, 1740-1730, 1700-1690 cm<-1>IR: 3600, 3500-3400, 1740-1730, 1700-1690 cm<-1>
Eksempel 49: (lia, 15R9-16-n-buty'l-ll, 15/dihydroksy-9-okso-2,3-(-)-trans-metylen-prostansyre Example 49: (11a, 15R9-16-n-butyl'1-11,15/dihydroxy-9-oxo-2,3-(-)-trans-methylene-prostanic acid
IR. 3600, 3500-3400, 1740-1730, 1695 cm<-1>Eksempel' 50(:s (lia, 15 R')-16-n-butyl-ll, 15-dihydrok sy-9-oteso-2, 3- (.+) - trans-metyl en-pros tansyre IR. 3600, 3500-3400, 1740-1730, 1695 cm <-1>Example' 50(:s (lia, 15 R')-16-n-butyl-11, 15-dihydro sy-9-oteso-2, 3 - (.+) - trans-methyl en-prostanic acid
IR: 3600, 3500-3300, 1740-1730, .1695 cm<-1>'" IR: 3600, 3500-3300, 1740-1730, .1695 cm<-1>'"
Eksempel 51: (15S)-15-hydroksy-9-okso-2,3-(-)-trans-metylen-post-10-ensyre Example 51: (15S)-15-hydroxy-9-oxo-2,3-(-)-trans-methylene-post-10-enoic acid
IR ' 3600-3400,1730-1680 cm"<1>IR ' 3600-3400,1730-1680 cm"<1>
EksempeF"52 : (15S)-15^hydroksy-9-oko-2, 3-( + ) -trans-metyl en-prost-10-ensyre Example F"52 : (15S)-15^hydroxy-9-oco-2,3-( + )-trans-methyl en-prost-10-enoic acid
IR 3600,3500-3400, 1730-1600 cm<-1>IR 3600,3500-3400, 1730-1600 cm<-1>
Eksempel 53: (15R)-16-n-butyl-15-hydroksy-9-okso-2,3-(-)-trans-metylen-prost-10-ensyre Example 53: (15R)-16-n-butyl-15-hydroxy-9-oxo-2,3-(-)-trans-methylene-prost-10-enoic acid
IR 3600-3400, 1730-1680 cm<-1>IR 3600-3400, 1730-1680 cm<-1>
Eksempel 54: (15R)-16-n-butyl-15-hydroksy-9-okso-2,3-(+)-trans-metylen-prost-10-ensyre Example 54: (15R)-16-n-butyl-15-hydroxy-9-oxo-2,3-(+)-trans-methylene-prost-10-enoic acid
IR 3600-3400, 1725-1685 cm"<1>IR 3600-3400, 1725-1685 cm"<1>
Eksempel 5.5: (15S)-16,.16-dimetyl-15-hydroksy-9-okso-2,3-(-)-trans-metylen-prost-10-ensyre Example 5.5: (15S)-16,.16-dimethyl-15-hydroxy-9-oxo-2,3-(-)-trans-methylene-prost-10-enoic acid
IR 3600-3400, 1730-1680 cm<-1>IR 3600-3400, 1730-1680 cm<-1>
Eksempel 56: (15R)-16,16-dimetyl-15-hydroksy-9-okso-2,3-(+)-trans-metylen-prost-10-ensyre Example 56: (15R)-16,16-dimethyl-15-hydroxy-9-oxo-2,3-(+)-trans-methylene-prost-10-enoic acid
IR 3600-3400, 1725-1680 cm"<1>IR 3600-3400, 1725-1680 cm"<1>
Eksempel 57 : .(9a, lia, 15S) -9,11,15-trihydroksy-2, 3-(-) - Example 57 : .(9a, 11a, 15S) -9,11,15-trihydroxy-2, 3-(-) -
trans-metylen-prostansyretrans-methylene-prostanic acid
IR 3600-3400, 1710-1680 cm"<1>IR 3600-3400, 1710-1680 cm"<1>
Eksempel 58: (9a,lia, 15S-9,11,15-trihydroksy-2,3-(+)-trans-metylen-prostansyre Example 58: (9a,11a, 15S-9,11,15-trihydroxy-2,3-(+)-trans-methylene-prostanic acid
IR 3600, 3500-3400, 1700-1690 cm"<1>IR 3600, 3500-3400, 1700-1690 cm"<1>
Eksempel 59: (9a,lla,13E, 15R)-16,16-dimetyl-9,11,15-trihydroksy-2,3-(-)-trans-metylen-prost-13-ensyre Example 59: (9a,lla,13E,15R)-16,16-dimethyl-9,11,15-trihydroxy-2,3-(-)-trans-methylene-prost-13-enoic acid
IR 3600-3400, 1695 cm"<1>IR 3600-3400, 1695 cm"<1>
Eksempel 60: (lla,13E, 15R)-11,15-dihyrroksy-16,16-dimetyl-9-okso-2,3-(-)-trans/metylen-prost-13-ensyre Example 60: (lla,13E,15R)-11,15-dihydroxy-16,16-dimethyl-9-oxo-2,3-(-)-trans/methylene-prost-13-enoic acid
IR 3600-3400, 1735, 1690 cm"<1>IR 3600-3400, 1735, 1690 cm"<1>
Eksempel 61: (13E, 15R)-16,16-dimetyl-15-hydrojsy-9-okso-2,3-(-)-trans/metylen-prosta-10,13-diensyre Example 61: (13E,15R)-16,16-dimethyl-15-hydroxy-9-oxo-2,3-(-)-trans/methylene-prosta-10,13-dienoic acid
IR 3600, 1695 cm"<1>IR 3600, 1695 cm"<1>
Eksempel 62: (9a, lia, 13E, 15S)-9,11,15-trihydroksy-2,3-(-)-trans-metylen-prost-13-ensyre Example 62: (9a, 11a, 13E, 15S)-9,11,15-trihydroxy-2,3-(-)-trans-methylene-prost-13-enoic acid
IR 3600-3400, 1695 cm"<1>IR 3600-3400, 1695 cm"<1>
Eksempel 63: (9a, lia, 13E, 15S)-9,11,15-trihydroksy-2,3-(rO - trans^metySen-prost-13-ensyre 3600,3500-3400, 1700-1690 cm"<1>Example 63: (9a, 11a, 13E, 15S)-9,11,15-trihydroxy-2,3-(rO-trans^methySen-prost-13-enoic acid 3600,3500-3400, 1700-1690 cm"<1 >
Eksempel 64: (lia, 13E, 15S)-11,15-dihydroksy-9-okso-2 , 3-(-)-trans-metylen-prost-13-ensyre Example 64: (11a, 13E, 15S)-11,15-dihydroxy-9-oxo-2,3-(-)-trans-methylene-prost-13-enoic acid
IR 3600-3400, 1735, 1690 cm<-1>IR 3600-3400, 1735, 1690 cm<-1>
Eksempel 65: (lia, 13E, 15S)-11,15-dihydroksy-9-okso-2, 3-( + ) -transrinetylen-prost-13-ensyre Example 65: (11a, 13E, 15S)-11,15-dihydroxy-9-oxo-2,3-( + )-transrinethylene-prost-13-enoic acid
IR 3600, 3500-3400, 1735, 1700-1690 cm"<1>IR 3600, 3500-3400, 1735, 1700-1690 cm"<1>
Eksempel 66: (13E, 15S)-15-hydroksy-9-okso-2,3-(-)-trans-metylen-prosta-10,13-diensyre Example 66: (13E, 15S)-15-hydroxy-9-oxo-2,3-(-)-trans-methylene-prosta-10,13-dienoic acid
IR 3600, 1720, 1695 cm<-1>IR 3600, 1720, 1695 cm<-1>
Eksempel 67: (13E, 15S)-15-hydroksy-9-okso-2,3-(-)-trans-metylen-prosta-10, 13-diensyre Example 67: (13E, 15S)-15-hydroxy-9-oxo-2,3-(-)-trans-methylene-prosta-10, 13-dienoic acid
IR 3600-3400, 1725-1710, 1700-1690 cm<-1>IR 3600-3400, 1725-1710, 1700-1690 cm<-1>
Eksempel 68: (5Z,lla, 13E, 15R)-11,15-dihydroksy-9-okso-16-(3'-trifluormetylfenoksy)-17,18,19,20-tetranor-2,3-(+)-trans-metyåen-prosta-5,13-diensyre Example 68: (5Z,lla,13E,15R)-11,15-dihydroxy-9-oxo-16-(3'-trifluoromethylphenoxy)-17,18,19,20-tetranor-2,3-(+)- trans-methylene-prosta-5,13-dienoic acid
IR 3600-3400, 1740, 1690, 1590 cm"<1>IR 3600-3400, 1740, 1690, 1590 cm"<1>
Eksempel 69: (5Z, 9a,lia,13E,15R)-16-(3'-trifluoro-metylfenoksy)-9,11,15-trihydroksy-17,18,19,20-tetranor-2,3-(+)-trans-metylen-pros ta-5 , 13-diensyre Example 69: (5Z,9a,11a,13E,15R)-16-(3'-trifluoromethylphenoxy)-9,11,15-trihydroxy-17,18,19,20-tetranor-2,3-(+ )-trans-methylene-pros ta-5,13-dienoic acid
IR 3600-3300, 1690, 1590 cm<-1>IR 3600-3300, 1690, 1590 cm<-1>
Eksempel 70: (5Z,9a, lia, 13E, 15R)-16-(3'-trifluoro-metylfenoksy)-9,11-15-trihydroksy-17 ,-18 ,19 , 20-tetranor-2 , 3-(-)-trans-metylen prosta-5,13-diensyre Example 70: (5Z,9a,11a,13E,15R)-16-(3'-trifluoromethylphenoxy)-9,11-15-trihydroxy-17,-18,19,20-tetranor-2,3-( -)-trans-methylene prosta-5,13-dienoic acid
IR 3600-3300, 1690, 1590 cm"<1>IR 3600-3300, 1690, 1590 cm"<1>
Eksempel 71: (lia, 15R)-11, 15-dihydroksy-15-metyl-9-. Example 71: (11a, 15R)-11,15-dihydroxy-15-methyl-9-.
okso-2,3-(+)-trans-metylen-prostansyreoxo-2,3-(+)-trans-methylene-prostanic acid
IR 3600, 1740-1690 cm<-1>IR 3600, 1740-1690 cm<-1>
Eksempel 72: (15R)-15-hydroksy-15-metyl-9-okso-2,3-(+)-trans-metylen-prost-10-ensyre Example 72: (15R)-15-hydroxy-15-methyl-9-oxo-2,3-(+)-trans-methylene-prost-10-enoic acid
IR 1740-1640 cm"<1>IR 1740-1640 cm"<1>
Eksempel 73: (lia,15S)-11,15-dihydroksy-15-metyl-2,3-(+)-trans-metylen-9-pkso-prostansyre Example 73: (11a,15S)-11,15-dihydroxy-15-methyl-2,3-(+)-trans-methylene-9-pxo-prostanoic acid
IR 3600-3300, 1760-1660 cm"<1>IR 3600-3300, 1760-1660 cm"<1>
Eksempel 74: (15R)-15-hydroksy-9-okso-16-(3 *-trifluoro-metylfenoksy-17,18,19,20-tetranor-2,3-(+)-trans-metylen-prost-10-ensyre- Example 74: (15R)-15-hydroxy-9-oxo-16-(3*-trifluoro-methylphenoxy-17,18,19,20-tetranor-2,3-(+)-trans-methylene-prost-10 -monoacid-
metylestermethyl ester
IR 3600, 1735, 1710, 1595 cm<-1>IR 3600, 1735, 1710, 1595 cm<-1>
Eksempel 75: (lia,13E,15R)-11,15-dihydroksy-9-okso-16-(3'-trifluorometylfenoksy)-17,18,19,20-tetranor-2, 3-( + )-trans-metylen-prost-13'-ensyre-metylester Example 75: (11a,13E,15R)-11,15-dihydroxy-9-oxo-16-(3'-trifluoromethylphenoxy)-17,18,19,20-tetranor-2,3-( + )-trans- methylene-prost-13'-enoic acid methyl ester
IR 3600-3300, 1740, 1720, 1590 cm"'<1>IR 3600-3300, 1740, 1720, 1590 cm"'<1>
Eksempel 76: (lla-15R)-11,15-dihydroksy-9-okso-16-(3'-tri-fluormetylfenoksy)-17,18,19,20-tetranor-2,3-(+)-trans-metylen-prostansyre-metyléster Example 76: (11a-15R)-11,15-dihydroxy-9-oxo-16-(3'-trifluoromethylphenoxy)-17,18,19,20-tetranor-2,3-(+)-trans- methylene-prostanic acid methyl ester
IR 3600-3400, 1740, 1720, 1590 cm<-1>IR 3600-3400, 1740, 1720, 1590 cm<-1>
Eksempel 77: (5Z,13E,15R)-15-hydroksy-9-okso-16-(3'-trifluormetylfenoksy)-17,18,19,20-tetranor-2,3-(+)-trans-metylen-prost-5,10,13-triensyre Example 77: (5Z,13E,15R)-15-hydroxy-9-oxo-16-(3'-trifluoromethylphenoxy)-17,18,19,20-tetranor-2,3-(+)-trans-methylene- prost-5,10,13-trienoic acid
IR 3600, 1700, 1590 cm<-1>IR 3600, 1700, 1590 cm<-1>
Eksempel 78: ( 5Z, 9(3 , lia, 23E, 15R)-16,16-dimetyl-16-(3'-trifluorometylfenoksy)-9,11,15-trihydroksy-17,18,19,20-tetranor-2,3-(+)-trans-metylen-prosta-5,13-diensyre Example 78: (5Z, 9(3, 11a, 23E, 15R)-16,16-dimethyl-16-(3'-trifluoromethylphenoxy)-9,11,15-trihydroxy-17,18,19,20-tetranor- 2,3-(+)-trans-methylene-prosta-5,13-dienoic acid
IR 3600-3300, 1700-1690 cm<-1>IR 3600-3300, 1700-1690 cm<-1>
Eksempel 79: 5Z,9a,lia,13E,15R)-16,16-dimetyl-16-(3<1->trifluorometylfenoksy)-9,11,15-trihydroksy-17,18,19T20-tetranor-2,3-(+)-trans-métylen-prosta-5,13-diensyre Example 79: 5Z,9a,lia,13E,15R)-16,16-dimethyl-16-(3<1->trifluoromethylphenoxy)-9,11,15-trihydroxy-17,18,19T20-tetranor-2,3 -(+)-trans-methylene-prosta-5,13-dienoic acid
IR 3600, 3350, 1690 cm"<1>IR 3600, 3350, 1690 cm"<1>
Eksempel 80: (5Z,9a,lia,13E,15R)-16,16-dimetyl-16-(3'-trifluorometylfenoksy)-9,11,15-trihydroksy-17,18,19,20-tetranor-2,3-(-)-trans-metyl en-pros ta-5 ,13-diensyre Example 80: (5Z,9a,11a,13E,15R)-16,16-dimethyl-16-(3'-trifluoromethylphenoxy)-9,11,15-trihydroxy-17,18,19,20-tetranor-2, 3-(-)-trans-methyl en-pros ta-5,13-dienoic acid
IR 3500-33.00, 1700-1680 cm"<1>IR 3500-33.00, 1700-1680 cm"<1>
Eksempel 81: (9a,lia,13E,15S,16R)-16-metyl-9,11,15-tr i hy drok sy-2 ,3-(-)-trans-metylen-prost-13-ensyre Example 81: (9a,11a,13E,15S,16R)-16-methyl-9,11,15-trihydroxy-2,3-(-)-trans-methylene-prost-13-enoic acid
IR 3400,1720-1695 cm"<1>IR 3400,1720-1695 cm"<1>
Eksempel 82: (lia,15R,16R)-11,15-dihydroksy-16-metyl-9-okso-2,3-(-)-trans-metylen-prostansyre Example 82: (11a,15R,16R)-11,15-dihydroxy-16-methyl-9-oxo-2,3-(-)-trans-methylene-prostanic acid
IR 3600-3300, 1740-1690 cm"1 IR 3600-3300, 1740-1690 cm"1
Eksempel 83:' (15R,16R-15-hydroksy-16-metyl-9-okso-2,3-(-)-trans-metylen-prost-10-ensyre IR 3600, 3500-3400, 1710-1695■cm"<1>Example 83: (15R,16R-15-hydroxy-16-methyl-9-oxo-2,3-(-)-trans-methylene-prost-10-enoic acid IR 3600, 3500-3400, 1710-1695■cm "<1>
Eksempel 84: (13E, 15S,16R)-15-hydroksy-16-metyl-9-okso-2,3-(-)-trans-metylen-prosta-10,13-diensyre Example 84: (13E,15S,16R)-15-hydroxy-16-methyl-9-oxo-2,3-(-)-trans-methylene-prosta-10,13-dienoic acid
IR 3600, 3500, 1730-1695 cm"<1>IR 3600, 3500, 1730-1695 cm"<1>
Eksempel 85: (5Z,lia,15R,16R)-11,15-dihydroksy-16-metyl-9-okso-2,3-(-)-trans-metylen-pros t-5-ensyre Example 85: (5Z,11a,15R,16R)-11,15-dihydroxy-16-methyl-9-oxo-2,3-(-)-trans-methylene-pros t-5-enoic acid
IR 3600-3350, 1735-1685 cm"<1>IR 3600-3350, 1735-1685 cm"<1>
Eksempel 86: (5Z,lla,15R, 16R)-11,15-dihydroksy-16-metyl-9-okso-2,3-(-)-trans-metylen-pros t-5 -ensyr erne tyl ester Example 86: (5Z,11a,15R,16R)-11,15-dihydroxy-16-methyl-9-oxo-2,3-(-)-trans-methylene-pros t-5-enic acid ethyl ester
IR 3600-3450, 1750-1700 cm"<1>IR 3600-3450, 1750-1700 cm"<1>
Eksempel 87: (5Z,13E,15R)-16,16-dimetyl-15-hydroksy-9-okso-16-(3'-trifluorornetyl fenoksyl)-17,18,19,20-tetranor-2,3-(+)-trans-métylen prosta-5,10,13-triensyre Example 87: (5Z,13E,15R)-16,16-dimethyl-15-hydroxy-9-oxo-16-(3'-trifluoroethyl phenoxyl)-17,18,19,20-tetranor-2,3-( +)-trans-methylene prosta-5,10,13-trienoic acid
IR 3600-3500, 1720-1680 cm<-1>IR 3600-3500, 1720-1680 cm<-1>
Eksempel 88: (5Z,lia,13E,15R)-11,15-dihydroksy-16,16-dimetyl-9-okso-16-(3'-trifluorometyl-f enoksy)-17,18,19, 20-tetr anor-2 , 3T£+)-trans-metylen-prosta-5,13-diensyre Example 88: (5Z,11a,13E,15R)-11,15-dihydroxy-16,16-dimethyl-9-oxo-16-(3'-trifluoromethyl-phenoxy)-17,18,19,20-tetr anor-2 , 3T£+)-trans-methylene-prosta-5,13-dienoic acid
IR 3700-3500, 1760-1720, 1720-1680 cm<-1>IR 3700-3500, 1760-1720, 1720-1680 cm<-1>
Eksempel 89: .(5Z, 15R, 16.R)-15-hydroksy-16-metyl-9-okso-2,3-C-)-trans-metylen-prosta-5,10-diensyre - Example 89: .(5Z,15R,16.R)-15-hydroxy-16-methyl-9-oxo-2,3-C-)-trans-methylene-prosta-5,10-dienoic acid -
IR 3600-3400, 1740-1670 cm"<1>IR 3600-3400, 1740-1670 cm"<1>
Eksempel 90: (5Z,9a,lia,13E,15R)-16,16-dimetyl-9,11,15-tr ihydroksy-2,3-(+)-trans-metylen-prosta-5,13-diensyredifenyImetylester Example 90: (5Z,9a,11a,13E,15R)-16,16-dimethyl-9,11,15-trihydroxy-2,3-(+)-trans-methylene-prosta-5,13-diene acid diphenyl methyl ester
IR 3600, 3400, 1720-1715 cm<-1>IR 3600, 3400, 1720-1715 cm<-1>
Eksempel 91: (lia,13E,15S,16R)-11,15-dihydroksy-16-me tyl -9-okso-2 ,3-(-)-trans-metylen-prost-13-ensyredecanylester Example 91: (11a,13E,15S,16R)-11,15-dihydroxy-16-methyl-9-oxo-2,3-(-)-trans-methylene-prost-13-enoic acid decanyl ester
IR 3600, 1745, 1725, 1695 cm<-1>IR 3600, 1745, 1725, 1695 cm<-1>
Eksempel 92: (11(3, 13E,15S)-11,15-dihydroksy-9-okso-2,3-(+)-trans-metylen-8,12-epi-prost-13-ensyre IR 3600, 3500-2600, 1740, 1695 cm"<1>Example 92: (11(3,13E,15S)-11,15-dihydroxy-9-oxo-2,3-(+)-trans-methylene-8,12-epi-prost-13-enoic acid IR 3600, 3500 -2600, 1740, 1695 cm"<1>
Eksempel 93: (13E,15S)-15-hydroksy-9-okso-2,3-(+)-trans-metylen-9,12-epi-prost-10,13-diensyre IR 3600, 3500-2600, 1700 cm<-1>Example 93: (13E,15S)-15-hydroxy-9-oxo-2,3-(+)-trans-methylene-9,12-epi-prost-10,13-dienoic acid IR 3600, 3500-2600, 1700 cm<-1>
Eksempel 94: (15S)-15-hydroksy-9-okso-2,3-(+)-trans-metylen-8,12-epi-prostansyre Example 94: (15S)-15-hydroxy-9-oxo-2,3-(+)-trans-methylene-8,12-epi-prostanic acid
IR 3600, 3500-2600, 1735 .cm"1 IR 3600, 3500-2600, 1735 .cm"1
Eksempel 95: d,1-(5Z,9a,lia,13E,15R)-16-(3•-trifluoro-metylf enoksy)-9,11,15-trihydroksy-17,18,19,20-tetranor-2,3-(+)-trans-metylen-prosta-5,13-diensyre Example 95: d,1-(5Z,9a,1ia,13E,15R)-16-(3•-trifluoromethylphenoxy)-9,11,15-trihydroxy-17,18,19,20-tetranor-2 ,3-(+)-trans-methylene-prosta-5,13-dienoic acid
IR 3600-3300,1690, 1590 cm"<1>IR 3600-3300,1690, 1590 cm"<1>
Claims (2)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1159375 | 1975-09-05 | ||
| CH1628175 | 1975-12-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO762960L true NO762960L (en) | 1977-03-08 |
Family
ID=25708612
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO762960A NO762960L (en) | 1975-09-05 | 1976-08-27 |
Country Status (14)
| Country | Link |
|---|---|
| JP (1) | JPS5233656A (en) |
| AU (1) | AU1749676A (en) |
| DE (1) | DE2638401A1 (en) |
| DK (1) | DK391076A (en) |
| ES (1) | ES451202A1 (en) |
| FI (1) | FI762467A7 (en) |
| FR (1) | FR2322594A1 (en) |
| GB (1) | GB1554925A (en) |
| IL (1) | IL50408A0 (en) |
| NL (1) | NL7609710A (en) |
| NO (1) | NO762960L (en) |
| NZ (1) | NZ181935A (en) |
| PT (1) | PT65553B (en) |
| SE (1) | SE7609505L (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08880B2 (en) * | 1984-12-12 | 1996-01-10 | 住友ダウ株式会社 | Resin composition with excellent chemical resistance |
| JPH0757836B2 (en) * | 1984-12-14 | 1995-06-21 | 住友ダウ株式会社 | Resin composition |
| JP2003064231A (en) * | 2001-08-29 | 2003-03-05 | Asahi Kasei Corp | Weather and impact resistant styrenic resin composition |
| US6720386B2 (en) | 2002-02-28 | 2004-04-13 | General Electric Company | Weatherable styrenic blends with improved translucency |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO742378L (en) * | 1973-07-09 | 1975-02-03 | Sandoz Ag |
-
1976
- 1976-08-26 DE DE19762638401 patent/DE2638401A1/en not_active Withdrawn
- 1976-08-27 FI FI762467A patent/FI762467A7/fi not_active Application Discontinuation
- 1976-08-27 SE SE7609505A patent/SE7609505L/en unknown
- 1976-08-27 NO NO762960A patent/NO762960L/no unknown
- 1976-08-27 DK DK391076A patent/DK391076A/en unknown
- 1976-09-01 NL NL7609710A patent/NL7609710A/en not_active Application Discontinuation
- 1976-09-02 GB GB36369/76A patent/GB1554925A/en not_active Expired
- 1976-09-03 IL IL50408A patent/IL50408A0/en unknown
- 1976-09-03 PT PT65553A patent/PT65553B/en unknown
- 1976-09-03 ES ES451202A patent/ES451202A1/en not_active Expired
- 1976-09-03 NZ NZ181935A patent/NZ181935A/en unknown
- 1976-09-04 JP JP51105447A patent/JPS5233656A/en active Pending
- 1976-09-06 FR FR7626743A patent/FR2322594A1/en active Granted
- 1976-09-06 AU AU17496/76A patent/AU1749676A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| ES451202A0 (en) | 1977-11-16 |
| FR2322594B1 (en) | 1979-09-07 |
| DK391076A (en) | 1977-03-06 |
| FI762467A7 (en) | 1977-03-06 |
| PT65553A (en) | 1976-10-01 |
| GB1554925A (en) | 1979-10-31 |
| JPS5233656A (en) | 1977-03-14 |
| NL7609710A (en) | 1977-03-08 |
| DE2638401A1 (en) | 1977-03-17 |
| NZ181935A (en) | 1978-09-20 |
| IL50408A0 (en) | 1976-11-30 |
| FR2322594A1 (en) | 1977-04-01 |
| ES451202A1 (en) | 1977-11-16 |
| PT65553B (en) | 1978-10-10 |
| AU1749676A (en) | 1978-03-16 |
| SE7609505L (en) | 1977-03-06 |
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