WO1988007537A1 - NOVEL PROSTAGLANDIN INTERMEDIATES MODIFIED IN THE omega-CHAIN AND PROCESS FOR PREPARING SAME - Google Patents

NOVEL PROSTAGLANDIN INTERMEDIATES MODIFIED IN THE omega-CHAIN AND PROCESS FOR PREPARING SAME Download PDF

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Publication number
WO1988007537A1
WO1988007537A1 PCT/HU1988/000016 HU8800016W WO8807537A1 WO 1988007537 A1 WO1988007537 A1 WO 1988007537A1 HU 8800016 W HU8800016 W HU 8800016W WO 8807537 A1 WO8807537 A1 WO 8807537A1
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formula
compound
cyclopentyl
alkyl group
cyclohexyl group
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PCT/HU1988/000016
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French (fr)
Inventor
István KÁLDOR
Vilmos Simonidesz
Péter GYÓRY
Ferencné SZABÓ
János O^"RI
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Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt.
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Publication of WO1988007537A1 publication Critical patent/WO1988007537A1/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/535Organo-phosphoranes
    • C07F9/5352Phosphoranes containing the structure P=C-
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C31/00Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C31/18Polyhydroxylic acyclic alcohols
    • C07C31/20Dihydroxylic alcohols
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C31/00Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C31/34Halogenated alcohols
    • C07C31/36Halogenated alcohols the halogen not being fluorine
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/54Quaternary phosphonium compounds
    • C07F9/5407Acyclic saturated phosphonium compounds

Definitions

  • This invention relates to novel p rost aglandin intermediates. According to an other aspect of the invention, there is provided a process for the preparation of these compounds.
  • the vinyl cuprate reagent of the formula (XIIl) is obtained by reacting a tetrahydrof uran solution of the vinyllithium compound of the formula (9) with an ethereal solution of copper (I)pentyne solvated with hexamethylphosphoric acid triamide (HMP).
  • HMP hexamethylphosphoric acid triamide
  • the phosphorane of the formula (la) may be prepared according to Scheme C)
  • R means a straight or branched chain C 1-6 alkyl group optionally substituted by a cyclopentyl or cyclohexyl group; or a cyclopentyl or cyclohexyl group; and R 1 means a C 1-4 alkyl group, with a C 1-6 alkyl bromoacetate and zinc powder (Reformatskii synthesis); then reacting the thus obtained compound of the formula (Vl),
  • a preferred embodiment of the process of the invention is as follows.
  • a compound of the formula (VIl) is reacted with zinc metal and ethyl bromoacetate or an other C 1-6 alkyl bromoacetate in tetiahydrofuran or in an other solvent commonly used in the Reformatskii synthesis.
  • the resulting compound of the formula (VI) is reduced by a complex metal hydride, preferably by lithium aluminium hydride (LAH) in tet rahydrofuran or in an other solvent commonly used in the metal hydride reductions.
  • LAH lithium aluminium hydride
  • the primary hydroxyl group of the resulting compound of formula (V) is replaced by bromine by using a system consisting of carbon tetrabromide and triphenylphosphine in acetonitrile solvent, whereafter bromine in the thus prepared compound of the formula (IV) is replaced by iodine by using an alkaline metal iodide, preferably sodium iodide in acetone medium to give a compound of the formula (Ill) which in turn is refluxed with 10 to 15 molar equivalent of triphenylphosphine in acetonitrile to give a phosphonium salt of the formula (ll).
  • bromine in the thus prepared compound of the formula (IV) is replaced by iodine by using an alkaline metal iodide, preferably sodium iodide in acetone medium to give a compound of the formula (Ill) which in turn is refluxed with 10 to 15 molar equivalent of triphenylphosphine in acetonitrile
  • the compounds of the formulae (Vl), (V) (IV), (Ill) and (ll) prepared according to our invention are stable and can be isolated thus, their purification can advantageously be achieved.
  • the compounds of the formulae (Ill) to (Vl) may be purified by distillation or chromatography whereas the salt-like compounds of the formula (ll) are purified by chromatography or recrystallization.
  • An additional and unexpected advantage of the reaction route of the invention consists in that the compounds of the formula (V) are most easy to selectively brominate in a nearly quantitative yield while the tertiary hydroxyl group remains unchanged.
  • the compounds of the formula (ll) can be transformed to compounds of the formula (I) by using 2 molar equivalents of an alkyllithium or lithium alkylamide type compound . Lithium iodide arising as a side product in this reaction increases the trans-selectivity of the Wittig reaction of the compounds of formulae (XV), (XVl) or (XVIl) with the compound of the formula (I) [Tetrahedron Lett. 26, (3) 311 (1985); J. Am. Chem. Soc. 103, 2823 (1981); as well as Liebigs Ann. Chem. 708, 1 (1967)].
  • Ethyl 3(R,S)-hydroxy-3-methylheptanoate 27.5 mi of ethyl bromoacetate and 35 ml of 2-hexanone are simultaneously portionwise added to a suspension of 17.5 g of dry zinc powder in 150 ml of abs. tetrahydrofuran at the boiling temperature within 30 minutes (the reaction is exothermic). After the addition, the reaction mixture is refluxed for additional 90 minutes, then cooled to room temperature and decomposed by adding a mixture of 100 ml of water and 20 ml of acetic acid at such a rate that the temperature does not exceed 30 °C.

Abstract

The invention relates to the preparation of compounds of formula (I), wherein R means a straight or branched chain C1-6 alkyl group optionally substituted by a cyclopentyl or cyclohexyl group; or a cyclopentyl or cyclohexyl group; and R1 stands for a C1-4 alkyl group. The invention relates also to the new intermediates of formula (II), formula (III), formula (IV) and formula (V).

Description

NOVEL PROSTAGLANDIN INTERMEDIATES MODIFIED IN THE ω-CHAIN AND PROCESS FOR PREPARING SAME
This invention relates to novel p rost aglandin intermediates. According to an other aspect of the invention, there is provided a process for the preparation of these compounds.
It is known that several prostaglandin-E (PGE) derivatives exert a remarkable gastric secretion-inhibiting and cytoprotective effect. Such compounds are e.g. misoprostol of the formula (VIIl)
Figure imgf000003_0001
and rioprostil of the formula (IX)
Figure imgf000003_0002
[Drugs of the Future 2 , 817 (1977); ibid. 10, 207 (1985)].
The above compounds are prepared in a way known from the literature [Tetrahedron Lett. 48, 4217 (1975); as well as US-PS No. 4,l32,738j according to the Scheme A)
Figure imgf000004_0001
via a conjugate addition of a cyclopent-1-enealkanecarboxylic acid ester of the formula (Xl)
Figure imgf000005_0001
or cyclopent-1-enealcohol of the formula (XII)
Figure imgf000005_0002
protected by te trahydropy ranyl (THP) group, with the vinyl cuprate reagent of the formula (XIIl)
Figure imgf000005_0003
The preparation of the vinyl cuprate of the formula (XIIl) is known from the literature [J. Med. Chem. 20, 1152 (1977); as well as BE-PS No. 827,127 and US-PS No. 4,087, 447 ] as shown in Scheme B).
Figure imgf000006_0001
According to Scheme B) the tr im ethyIsilyl-protected 4-methyl-1-octine-4(RS)-ol of the formula (4)
Figure imgf000007_0001
which can be obtained by reacting 2-hexanone with propargylmagnesium bromide in a Grignard reaction followed by trimethylsilylation, is transformed through stereoselective hydroborat ion, hydroalumination or hydrostannation to the corresponding trans-vinylborane, -alane or -stannane compounds of the formula (5), (6) or (7), respectively
Figure imgf000007_0002
Figure imgf000007_0003
Figure imgf000007_0004
from which the corresponding trans-iodoalkene of the formula (8)
Figure imgf000008_0001
is obtained with elementary iodine. From the thus obtained iodoalkene of the formula (8) or vinylstannane of the formula (7), the appropriate trans-vinyllithium compound of the formula (9)
Figure imgf000008_0002
is prepared by transmetalation carried out with n-butyllithium. The vinyl cuprate reagent of the formula (XIIl) is obtained by reacting a tetrahydrof uran solution of the vinyllithium compound of the formula (9) with an ethereal solution of copper (I)pentyne solvated with hexamethylphosphoric acid triamide (HMP). In addition to the complicateness, the carrying out of these reactions requires very high accuracy, particular conditions, extreme purity and anhydrousness of the reagents and solvents. A more recent synthesis of the compounds of formulae (VIII), (ix) and (XIV)
Figure imgf000009_0001
may be achieved in such a way that the ∞-chain is built up by reacting the compound of the formula (XV)
Figure imgf000009_0002
or formula (XVI)
Figure imgf000009_0003
with the phosphorane of the formula (la)
Figure imgf000009_0004
in a trans-selective Witting reaction [Tetrahedron
Lett. 23, (10) 1067 (1982)].
The phosphorane of the formula (la) may be prepared according to Scheme C)
Figure imgf000010_0001
wherein all the intermediates of the reaction series are unisolable reactive substances whereby any way of purification is excluded.
If is obvious that the known solutions involve important drawbacks from the viewpoint of an industrial realization.
In order to eliminate these disadvantages, a novel method has been sought for preparing the intermediates of the formula (i)
Figure imgf000011_0001
and (la).
Surprisingly, it has been found that the intermediates of the formula (i) can be obtained by reacting an oxo compound of the formula (VIl),
Figure imgf000011_0002
wherein
R means a straight or branched chain C1-6 alkyl group optionally substituted by a cyclopentyl or cyclohexyl group; or a cyclopentyl or cyclohexyl group; and R1 means a C1-4 alkyl group, with a C1-6 alkyl bromoacetate and zinc powder (Reformatskii synthesis); then reacting the thus obtained compound of the formula (Vl),
Figure imgf000012_0001
wherein R and R1 are the same as defined above, with a metal hydride; reacting the thus prepared compound of the formula (V),
Figure imgf000012_0002
wherein R and R1 are the same as defined above, with triphenylphosphine and carbon tet rabromide; then transforming the obtained compound of the formula (iv), wherein R and R1 are the same as defined above, with an inorganic iodine compound; reacting the thus obtained compound of the formula (Ill),
Figure imgf000013_0001
wherein R and R1 are the same as defined above, with triphenylphosphine; and transforming the thus prepared novel phosphonium salt of the formula (Il)
Figure imgf000013_0002
with 2 molar equivalents of an alkyllithium or lithium alkylamide type compound in one step to give the intermediate of the formula (I).
A preferred embodiment of the process of the invention is as follows. A compound of the formula (VIl) is reacted with zinc metal and ethyl bromoacetate or an other C1-6 alkyl bromoacetate in tetiahydrofuran or in an other solvent commonly used in the Reformatskii synthesis. The resulting compound of the formula (VI) is reduced by a complex metal hydride, preferably by lithium aluminium hydride (LAH) in tet rahydrofuran or in an other solvent commonly used in the metal hydride reductions. Thereafter, the primary hydroxyl group of the resulting compound of formula (V) is replaced by bromine by using a system consisting of carbon tetrabromide and triphenylphosphine in acetonitrile solvent, whereafter bromine in the thus prepared compound of the formula (IV) is replaced by iodine by using an alkaline metal iodide, preferably sodium iodide in acetone medium to give a compound of the formula (Ill) which in turn is refluxed with 10 to 15 molar equivalent of triphenylphosphine in acetonitrile to give a phosphonium salt of the formula (ll).
The compounds of the formulae (Vl), (V) (IV), (Ill) and (ll) prepared according to our invention are stable and can be isolated thus, their purification can advantageously be achieved. The compounds of the formulae (Ill) to (Vl) may be purified by distillation or chromatography whereas the salt-like compounds of the formula (ll) are purified by chromatography or recrystallization.
The compounds of the formulae (ll) to (v) prepared according to our invention are novel.
An additional and unexpected advantage of the reaction route of the invention consists in that the compounds of the formula (V) are most easy to selectively brominate in a nearly quantitative yield while the tertiary hydroxyl group remains unchanged. As mentioned hereinbefore, the compounds of the formula (ll) can be transformed to compounds of the formula (I) by using 2 molar equivalents of an alkyllithium or lithium alkylamide type compound . Lithium iodide arising as a side product in this reaction increases the trans-selectivity of the Wittig reaction of the compounds of formulae (XV), (XVl) or (XVIl) with the compound of the formula (I) [Tetrahedron Lett. 26, (3) 311 (1985); J. Am. Chem. Soc. 103, 2823 (1981); as well as Liebigs Ann. Chem. 708, 1 (1967)].
The process of the invention is illustrated in detail by the following non-limiting Examples.
Example 1
Ethyl 3(R,S)-hydroxy-3-methylheptanoate 27.5 mi of ethyl bromoacetate and 35 ml of 2-hexanone are simultaneously portionwise added to a suspension of 17.5 g of dry zinc powder in 150 ml of abs. tetrahydrofuran at the boiling temperature within 30 minutes (the reaction is exothermic). After the addition, the reaction mixture is refluxed for additional 90 minutes, then cooled to room temperature and decomposed by adding a mixture of 100 ml of water and 20 ml of acetic acid at such a rate that the temperature does not exceed 30 °C. After the decomposition, the phases are separated and the aqueous phase is extracted 3 times with 80 ml of ethyl acetate each. After that the solvent is removed from the combined organic phases, which are then subjected to fractional distillation to give 35.3 g (76%) of the title compound, b.p. 68-70 °C at 2 Hgmm. 1H-NMR (CDCl3, with TKS as internal standard, δ ppm): 0.9 t (3H); 1-1.5 m (11H); 2.5 s (3H) ; 3.5 s
(1H); 4.2 q (2H). Example 2
2(R,S)-Hydroxy-2-(2-hydroxyethyl) hexane 2 g of lithium aluminium hydride are carefully added in little portions to a solution of 9 g of ethyl 3(R,S)-hydroxy-3-methylheptanoate in 50 ml of abs. tetrahydrofuran at room temperature, then the temperature is increased to 40 ºC and the reaction is followed by chromatography [with a developing system of a 4:1 vol./ /vol. mixture of hexane and ethyl acetate on a Kieselgel 60 F254 (herck) sheet, by detecting with an 5% ethanolic phosphomolybdenic acid solution with heating to 150 ºC; the Rf value of the starting material is 0.4, that of the title product is 0.1]. When no starting material, may be observed in the reaction mixture, the reaction mixture, the excess lithium aluminium hydride is decomposed by adding 10 ml of ethyl acetate and then diluted (carefully) with 50 ml of water. The precipitated lithium and aluminium salts are filtered off and the phases of the mother liquor are separated. The aqueous phase is extracted 3 times with 20 ml of ethyl acetate each, the organic phases are combined and the solvent is removed. The residue is purified by column chromatography to give
5.7 g (82%) of the title compound. 1H-uncoupled 13C-NMR (CDCl3 with TKS as internal standard, δ ppm): 14.1; 23.3; 26.3; 26.5; 41.4; 42.3; 59.4; 73.4; 73.8.
Example 3
2-(2-Bromoethyl)-2(R,S)-hydroxyhexane 4.7 g of triphenylphosphine are added to a solution of 2.4 g of 2(R,S)-hydroxy-(2-hydroxyethyl)-hexane in 10 ml of acetonitrile. Then, 5.1 g of carbon tetrabromide are portionwise added to the suspension obtained at room temperature, the reaction solution is stirred for 3 hours. The reaction is followed by chromatography (under the same conditions as described in Example 2, the Rf value of the title compound is 0.5). At the end of the reaction, the solvent is removed and the residue is purified by column chromatography with a column of 2 cm in diameter, with a charge height of 20 cm of Kieselgel 60 F254 (Merck); a 4:1 vol./vol. mixture of hexane and ethyl acetate is used as eluent under a pressure of 2 bar. Thus 3.3 g (97%) of the title compound are obtained. H-NMR (CDCl3 with TMS as internal standard, δ ppm):
0.9 t (3H); 1.2 s (3H); 1.2-1.5 m (7H); 1.95-2.2 m (2H); 3.4-3.6 m (2H). Example 4 2(R,S)-Hydroxy-2-(2-iodoethyl)hexane
A solution containing 2.1 g of 2-(2-bromoethyl-2(R,S)-hydroxy-hexane in 10 ml of acetone saturated with sodium iodide is refluxed for 30 minutes, then the acetone is distilled off. The residue is taken up in 15 ml of n-hexane, filtered and the salts filtered out are washed 3 times with 10 ml of n-hexane each. The combined n-hexane phases are evaporated to give 2.3 g (90 %) of the title compound. 1H-NMR (CDCl3 with TMS as internal standard, δppm): 0.92 t (3H); 1.17 s (3H); 1.2-1.6 m (7H);
2.03-2.22 m (2H); 3.15-3.35 m (2H) 1H-uncoupled 3C-NMR (CDCl3 with TMS as internal standard, δ ppm): -0.55; 14.0; 23.1; 25.0; 25.3; 41.6; 46.8; 74.0. Example 5
3(R,S)-Hydroxy-3-methyl-1-heptyl-triphenylphosphonium iodide
A mixture containing 2 g of 2(R,S)-hydroxy-2-(2-iodoethyl)hexane, 20 g of triphenylphosphine and 20 ml of acetonitrile is refluxed for 8 hours, then the disappearance of the starting material is observed by chromatography (under the same conditions as described in Example 2, the Rf value of the starting iodine compound is 0.5). At the end of the reaction, the mixture is cooled to room temperature, triphenylphosphine is filtered off and washed twice with 20 ml of acetonitrile each. The acetonitrile washings and the mother liquor are combined and the solvent is removed. The residue is purified by removing the excess triphenylphosphine with chromatography on the column ard under conditions described in Example 3. Triphenylphosphine is eluted by ethyl acetate then, the title product is eluted by a 2:1 vol./vol. mixture of acetone and ethyl acetate. Thereafter, the solvent is carefully evaporated from the product under reduced pressure which is then crystallized while stirring with hexane at room temperature. Thus 3.4 g (84%) of the title compound are obtained, m.p.; 128-130 °C. 1H-NMR (CDCl3 with TMS as internal standard, δppm): 0.85 t (3H); 1.3 s (3H); 1.4-1.9 m (8H);
3.4-3.85 m (3H); 7.7-8 m (15 H)
1H-uncoupled 13C-NMR (CDCl3 with TMS as internal standard, δ ppm) : 14.1 (C7); 17.5; 19.6 (C2);
23.0 (C6); 26.1; 25.2 (C methyl); 33.9; 34.0 (C4); 41.5 (C5); 71.8; 72.3 (C3);
116.4; 119.8 (C1); 130.4; 130.8; 133.3; 133.7;
135.2 (Caromatic).

Claims

Claims
1. A process for the preparation of compounds of the formula (I),
Figure imgf000019_0001
wherein
R means a straight or branched chain C1-6 alkyl group optionally substituted by a cyclopentyl or cyclohexyl group; or a cyclopentyl or cyclohexyl group; and R1 stands for a C1-4 alkyl group, which comprises reacting a compound of the formula
(VII),
Figure imgf000019_0002
wherein R and R1 are the same as defined above, with zinc metal and a C1-6 alkyl bromoacetate; then reacting the thus obtained compound of the formula (VI)
wherein R a
Figure imgf000019_0003
nd R1 are the same as defined above, by a metal hydride reacting the thus prepared ccmpoinds of the formula (V) ,
Figure imgf000019_0004
wherein R and R1 are the same as defined above, with triphenylphosphine and carbon tetrabromide; transforming the obtained compound of the formula (IV),
Figure imgf000020_0001
wherein R and R1 are the same as defined above, with an inorganic iodine compound; bringing into reaction the thus obtained iodine compound of the formula (Ill),
Figure imgf000020_0002
wherein R and R1 are the same as defined above, with triphenylphosphine; and reacting the thus prepared phosphonium salt of the formula (ll),
Figure imgf000020_0003
wherein R and R1 are the same as defined above, with an alkyllithium or a lithium alkylamide type compound to give the compound of the formula (I),
2. A process as claimed in claim 1, which comprises reacting a compound of the formula (VII) with ethyl bromoacetate and zinc metal in an anhydrous organic solvent.
3. A process as claimed in claim 1, which comprises using lithium aluminium hyαride as a metal hydride.
4. A process as claimed in claim 1, which comprises reacting a compound of the formula (v) with triphenylphosphine and carbon tetrabromide in an organic solvent, preferably in acetonitrile.
5. A process as claimed in claim 1, which comprises using an alkaline metal iodide, preferably sodium iodide as an iorganic iodine compound.
6. A process as claimed in claim 1, which comprises transforming a compound of the formula (ll) to a compound of the formula (i) by using an alkyllithium compound containing a C1-6 alkyl group or a C1-10 lithium dialkylamide or cycloalkylalkylamide compound.
7. Compounds of the formula (V),
Figure imgf000021_0001
where in
R means a straight or branched chain C1-6 alkyl group optionally substituted by a cyclopentyl or cyclohexyl group; or a cyclopentyl or cyclohexyl group; and R1 stands for a C1-6 alkyl group.
8. Compounds of the formula (IV),
Figure imgf000022_0001
whe rein R means a straight or branched chain C1-6 alkyl group optionally substituted by a cyclopentyl or cyclohexyl group; or a cyclopentyl or cyclohexyl group; and stands for a C1-4 alkyl group.
9. Compounds of the formula (Ill),
Figure imgf000022_0002
wherein R means a straight or branched chain C1-6 alkyl group optionally substituted by a cyclopentyl or cyclohexyl group; or a cyclopentyl or cyclohexyl group; and R1 stands for a C1-4 alkyl group.
10. Compounds of the formula (ll),
Figure imgf000022_0003
wherein
R means a straight or branched chain C1-6 alkyl group optionally substituted by a cyclopentyl or cyclohexyl group; or a cyclopentyl or a cyclohexyl group; and R1 stands for a C1-4 alkyl group.
11. 2(R,S)-Hydroxy-2-(2-hydroxyethyl) hexane.
12. 2-(2-Bromoethyl)-2(R,S)-hydroxyhexane.
13. 2(R,S)-Hydroxy-2-(2-iodoethyl) hexane.
14. 3(R,S)-Hydroxy-3-methyl-1-heptyl-triphenylphosphonium iodide.
PCT/HU1988/000016 1987-03-24 1988-03-23 NOVEL PROSTAGLANDIN INTERMEDIATES MODIFIED IN THE omega-CHAIN AND PROCESS FOR PREPARING SAME WO1988007537A1 (en)

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HU128187A HU198503B (en) 1987-03-24 1987-03-24 Process for producing triphenyl phosphonium salts
HU1281/87 1987-03-24

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WO2005097812A1 (en) * 2004-04-09 2005-10-20 Valorisation-Recherche, Société en Commandite Phosphonium salts derivatives and their use as solubility controlling auxiliaries
US7276531B2 (en) 2003-03-03 2007-10-02 Applied Research Systems Ars Holding N.V. G-lactam derivatives as prostaglandin agonists

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7276531B2 (en) 2003-03-03 2007-10-02 Applied Research Systems Ars Holding N.V. G-lactam derivatives as prostaglandin agonists
WO2005097812A1 (en) * 2004-04-09 2005-10-20 Valorisation-Recherche, Société en Commandite Phosphonium salts derivatives and their use as solubility controlling auxiliaries
US7880037B2 (en) 2004-04-09 2011-02-01 Valorisation-Recherche, Limited Partnership Phosphonium salts derivatives
US8067440B2 (en) 2004-04-09 2011-11-29 Valorisation-Recherche, Limited Partnership Phosphonium salts derivatives and uses thereof

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DD268247A5 (en) 1989-05-24
HUT46333A (en) 1988-10-28

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