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WO1988007537A1 - NOUVEAUX PRODUITS INTERMEDIAIRES DE PROSTAGLANDINE MODIFIES DANS LA CHAINE omega ET PROCEDE DE PREPARATION DESDITS PRODUITS - Google Patents

NOUVEAUX PRODUITS INTERMEDIAIRES DE PROSTAGLANDINE MODIFIES DANS LA CHAINE omega ET PROCEDE DE PREPARATION DESDITS PRODUITS 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
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
cyclopentyl
alkyl group
cyclohexyl group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/HU1988/000016
Other languages
English (en)
Inventor
István KÁLDOR
Vilmos Simonidesz
Péter GYÓRY
Ferencné SZABÓ
János O^"RI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chinoin Private Co Ltd
Original Assignee
Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt filed Critical Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Publication of WO1988007537A1 publication Critical patent/WO1988007537A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/535—Organo-phosphoranes
    • C07F9/5352—Phosphoranes containing the structure P=C-
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C31/00—Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C31/18—Polyhydroxylic acyclic alcohols
    • C07C31/20—Dihydroxylic alcohols
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C31/00—Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C31/34—Halogenated alcohols
    • C07C31/36—Halogenated alcohols the halogen not being fluorine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds
    • C07F9/5407—Acyclic 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.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à la préparation de composés représentés par la formule (I), où R représente un groupe alkyle de 1 à 6 atomes de carbone à chaîne droite ou ramifiée, éventuellement substitué par un groupe cyclopentyle ou cyclohexyle; ou un groupe cyclopentyle ou cyclohexyle; et R1 représente un groupe alkyle de 1 à 4 atomes de carbone. La présente invention se rapporte également aux nouveaux produits intermédiaires représentés par la formule (II), la formule (III), la formule (IV) et la formule (V).
PCT/HU1988/000016 1987-03-24 1988-03-23 NOUVEAUX PRODUITS INTERMEDIAIRES DE PROSTAGLANDINE MODIFIES DANS LA CHAINE omega ET PROCEDE DE PREPARATION DESDITS PRODUITS Ceased WO1988007537A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU1281/87 1987-03-24
HU128187A HU198503B (en) 1987-03-24 1987-03-24 Process for producing triphenyl phosphonium salts

Publications (1)

Publication Number Publication Date
WO1988007537A1 true WO1988007537A1 (fr) 1988-10-06

Family

ID=10953674

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU1988/000016 Ceased WO1988007537A1 (fr) 1987-03-24 1988-03-23 NOUVEAUX PRODUITS INTERMEDIAIRES DE PROSTAGLANDINE MODIFIES DANS LA CHAINE omega ET PROCEDE DE PREPARATION DESDITS PRODUITS

Country Status (5)

Country Link
CS (1) CS266349B2 (fr)
DD (1) DD268247A5 (fr)
HU (1) HU198503B (fr)
PL (1) PL153699B1 (fr)
WO (1) WO1988007537A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005097812A1 (fr) * 2004-04-09 2005-10-20 Valorisation-Recherche, Société en Commandite Derives de sels de phosphonium, utilisation de ces derniers en tant qu'adjuvants de regulation de la solubilite
US7276531B2 (en) 2003-03-03 2007-10-02 Applied Research Systems Ars Holding N.V. G-lactam derivatives as prostaglandin agonists

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF ORGANIC CHEMISTRY, Vol. 43, No. 4, issued 1978, W.G. SALMOND et al., " A Stereoselective Wittig reagent and its application to the synthesis of 25-hydroxylated vitamin D metabolites", 790-792. *
PATENT ABSTRACTS OF JAPAN, Unexamined applications, C field, Vol. 8, No. 130, (C229) (1567), issued 16 June 1984, The Patent Office Japanese Government, see page 107 C 229; & JP,A,59 042 330, (08.03.1984) (SUNTORY K.K.). *
SOVIET INVENTIONS ILLUSTRATED, section Ch, week C44, 720, 773-724, 077, issued 10 December 1980, Derwent Publications Ltd. London 1980, Pharmaceuticals p. 2, see Abstract-No. 78 517 C/44; & SU,A,722893 (UFA PETROLEUM INST). *
SOVIET INVENTIONS ILLUSTRATED, section Ch: Chemical, week 8416, 784 502-1 030 028, issued 30 May 1984, Derwent Publications Ltd., London 1984, see Abstract-No. 84 099 870/16, E16; & SU,A,1028657 A (AS UKR PHYS CHEM IN). *
SOVIET INVENTIONS ILLUSTRATED, section Ch: Chemical, week 8737, 421 304-1 288 505, issued 28 October 1987, Derwent Publications Ltd., London 1987, see Abstract-No. 87 262 303/37; & SU,A,1286588 A (UFA PETROLEUM INST). *
TETRAHEDRON LETTERS, Vol. 23, No. 10, issued 1982, CHIA-LIN J. WANG, "Azaprostanoids I. Synthesis of (rac)-8-aza-11-deoxy-15-deoxy-16 hydroxy-16-methylprostagandins", 1067-1070. *

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 (fr) * 2004-04-09 2005-10-20 Valorisation-Recherche, Société en Commandite Derives de sels de phosphonium, utilisation de ces derniers en tant qu'adjuvants de regulation de la solubilite
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

Also Published As

Publication number Publication date
PL271413A1 (en) 1989-03-06
DD268247A5 (de) 1989-05-24
CS266349B2 (en) 1989-12-13
HUT46333A (en) 1988-10-28
CS189888A2 (en) 1989-02-10
HU198503B (en) 1989-10-30
PL153699B1 (en) 1991-05-31

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