WO2008003737A1 - Procédé de production de 3,3'-dihydroxyisoréniératine et ses nouveaux produits intermédiaires - Google Patents

Procédé de production de 3,3'-dihydroxyisoréniératine et ses nouveaux produits intermédiaires Download PDF

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WO2008003737A1
WO2008003737A1 PCT/EP2007/056794 EP2007056794W WO2008003737A1 WO 2008003737 A1 WO2008003737 A1 WO 2008003737A1 EP 2007056794 W EP2007056794 W EP 2007056794W WO 2008003737 A1 WO2008003737 A1 WO 2008003737A1
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formula
cis
isomer
building block
phosphonium salt
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Hansgeorg Ernst
Hagen Jaedicke
Klaus Henrich
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Basf Se
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
    • C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
    • C07C403/08—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
    • C07C37/20—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms using aldehydes or ketones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/50—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions decreasing the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/18—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring monocyclic with unsaturation outside the aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
    • C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
    • C07C403/10—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by etherified hydroxy groups
    • 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
    • C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)
    • 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
    • C07F9/5456—Arylalkanephosphonium compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P23/00—Preparation of compounds containing a cyclohexene ring having an unsaturated side chain containing at least ten carbon atoms bound by conjugated double bonds, e.g. carotenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/09—Geometrical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • the present invention relates to a novel process for the preparation of 3,3'-Dihydroxyisorenieratin in the formula I, hereinafter referred to ⁇ , ⁇ -carotene-3,3'-diol, as well as novel intermediates of this method.
  • 3,3'-Dihydroxyisorenieratin ( ⁇ , ⁇ -carotene-3,3'-diol) of the formula I is used as a feed additive (broiler skin pigmentation: Riv Zootec Vet 1974, 1, 31-44, egg yolk pigmentation: Z Allg. Microbiol. (1970), 10 (4), 237-244) are of great interest.
  • DE 1593440 describes the synthesis of ⁇ , ⁇ -carotene-3,3'-diol of the formula I.
  • crocetine dialdehyde 1 is reacted with two equivalents of the phosphonium salt 2 in a double Wittig olefination according to the synthesis strategy C10 + C20 + C10 to form ⁇ , ⁇ -carotene-3,3'-diol of the formula I.
  • the phosphonium salt of the formula 2 required for this synthesis is prepared in a four-step sequence from 2,3,6-trimethyl-4-hydroxybenzaldehyde of the formula II.
  • Example 1 obtained from 14.6 g (89.02 mmol) of aldehyde of the formula II, only 6.4 g (11, 13 mmol) of the phosphonium salt of formula 2. This yield is not satisfactory.
  • R tetrahydropyranyl protecting group
  • radicals R 1 are identical or different, preferably identical and are a Ci-Cs-alkyl group, or the two radicals R 1 together represent a bivalent C2-Ci2-alkylene radical, that is, together with the atoms connecting them form a cyclic ketal, in particular a 5- or 6-ring ketal,
  • R 2 is an ether, silyl ether or acetal protecting group which can be converted by hydrolysis into hydroxyl
  • M 1 is Li, Na, K, MgCl, MgBr, MgI or Mgi / 2, the compound of the formula MIb being Isomer, Z-isomer or E / Z isomer mixture may be present
  • R 2 is an ether, silyl ether or acetal protecting group convertible into a hydroxy group by hydrolysis
  • Ci5-phosphonium salt of the formula IX by partial hydrogenation of the triple bond also IX is converted to the 5 Ci -phosphonium salt of the formula
  • step d preference is given to at least step d), particularly preferably at least steps d) and e), in particular steps a), b), c) d ) and e).
  • step a) of the process according to the invention a monoketal of the formula II
  • radicals R 1 are identical or different, in particular identical and are a Ci-Cs-, in particular Ci-C4-alkyl group, such as methyl, ethyl, n-propyl or n-butyl, or the two radicals R 1 together for one divalent C2-C12, in particular are C 2 -C 8 -alkylene radical, that is to say, together with the atoms which join them, form a cyclic ketal, in particular a 5- or 6-ring ketal,
  • R 4 , R 5 or R 6 independently of one another are hydrogen or C 1 -C 4 -alkyl, such as methyl, ethyl, n-propyl or n-butyl, in particular the cyclic ketals
  • R 2 is an ether, silyl ether or acetal protecting group which can be converted into a hydroxy group by hydrolysis, in particular for
  • M 1 is Li, Na, K, MgCl, MgBr, MgI or Mg / 2, in particular Li, Na, MgCl or MgBr, very particularly preferably Li, where the compound of the formula MIb is in the form of an E isomer, Z isomer or E / Z isomer mixture may be present
  • the monoketal of the formula II used in step a) can be prepared in known manner (Zh. Org. Khim. 26, 5, pp. 1087-1091, 1990. Engl. Translation pp. 936-940, 1990) from the known starting material 2, 3,5-trimethylbenzoquinone of the formula XI (Ullmanns Encyclopedia of Industrial Chemistry, Vol. A 27, p 485, 1969)
  • step a) Preference is given in step a) to a cyclic monoketal of the formula II-a or II-b.
  • R 4 , R 5 or R 6 independently of one another represent hydrogen or C 1 -C 4 -alkyl, in particular the monoketals of the formulas II-a-1 or II-b-1
  • the metallated alkynes of the formula IIIa and IIIb are obtainable from the known alkynes of the formulas IIIa-a (EP 633258) and IIIb-b (EP 5748), Illa-a Illb-b in which R 2 is an ether, silyl ether or acetal protecting group which can be converted by hydrolysis to a hydroxy group, preferably for
  • an alkyne of the formula IIIa-a is used.
  • step a) the monoketal of the formula II-b-1 with the metallated alkyne of the formula MIa, wherein R 2 is 0-CH (Me) -O-Et and M 1 is Li, becomes the cis building block of the formula IVa in which the two radicals R 1 together represent a divalent ethylene group and R 2 is 0-CH (Me) -O-Et (compound of formula IVa-1).
  • the alkynes of the formulas Illa-a and Illb-b are dissolved in an inert solvent such as, for example, gen or cyclic ethers or hydrocarbons by reaction with alkali or alkaline earth amides, hydrides, organolithium or Grignard reagents in the corresponding metalated alkynes of the formulas IMa or IMb transferred.
  • an inert solvent such as, for example, gen or cyclic ethers or hydrocarbons by reaction with alkali or alkaline earth amides, hydrides, organolithium or Grignard reagents in the corresponding metalated alkynes of the formulas IMa or IMb transferred.
  • Particularly preferred bases for the deprotonation of the alkyne are lithium amides or lithium organyls, here in particular butyllithium.
  • the molar ratio of the alkyne of the formulas Illa-a or Illb-b to the monoketal of the formula II is usually between 1: 1 to 1.5: 1, preferably between 1.05: 1 and 1.3: 1. Excess alkyne can separated from IVa or IVb by distillation and recycled into the synthesis.
  • the conversion of the triple bond in the cis building block of the formula IVa or IVb into a double bond to a cis building block of the formula IVa 'or IVb' is carried out with the aid of a reducing agent.
  • the reducing agents which can be used in principle are the complex aluminum hydrides described for the reduction of propargyl alcohols, in particular lithium aluminum hydride, diisobutylaluminum hydride and sodium bis (2-methoxyethoxy) aluminum dihydride (HeIv, Chim, Acta 73, 868, 1990).
  • the reduction is carried out in inert cyclic or open-chain ethers (diethyl ether, methyl tert-butyl ether, THF) or open-chain or cyclic hydrocarbons, such as. For example, hexane or toluene.
  • the cis building block of the formula IVa-1 is particularly preferably converted into a cis building block of the formula IVa'-1
  • the protective groups of a cis building block of the formula IVa, IVb, IVa 'or IVb' are cleaved off by hydrolysis, in particular acid hydrolysis, to give a deprotected cis building block of the formula Va or Vb,
  • R 2 is an ether, silyl ether or acetal protecting group which can be converted by hydrolysis to a hydroxy group, preferably
  • Both the hydrolysis of the protecting groups for the ketone function and the hydrolysis of the protected hydroxy functions in a cis building block of the formula IVa, IVb, IVa 'or IVb' to a deprotected cis building block of the formula Va or Vb is usually carried out in an inert solvent in the presence of water and catalytic amounts of a strong acid.
  • Suitable solvents are water-miscible or immiscible inert solvents, such as open-chain or cyclic ethers, e.g.
  • the cis building block of the formula IVa'-1 is deprotected to the Ci 5 building block of the formula Va'-a.
  • a deprotected cis-building block of the formula Va is converted by addition of two equivalents of vinyl ethyl ether into a cis-ketone of the formula VIa,
  • R 2 is -O-CH (Me) -O-CH 2 CH 3 .
  • a cis-ketone of the formula VIa or VIb is converted by reduction of the carbonyl group to a secondary cis-alcohol of the formula VIIa or VIIb,
  • all hydride reducing agents are suitable with which a keto group can be reduced to the alcohol, such as complex boron and aluminum hydrides such.
  • complex boron and aluminum hydrides such as Sodium borohydride, lithium aluminum hydride, diisobutylaluminum hydride or sodium bis (2-methoxyethoxy) aluminum dihydride.
  • a cis-ketone of the formula VIa is converted by reduction into a secondary cis-alcohol of the formula VIIa,
  • R 2 is -O-CH (Me) -O-CH 2 CH 3 .
  • the cis-ketone of the formula VIa and VIb prepared in process step b is preferred without isolation and without further workup in process step c) for the preparation of the secondary cis Alcohol of formula VIIa or VIIb used.
  • process step d the reaction of a secondary cis-alcohol of the formula VIIa or VIIb with a strong organic or inorganic acid HX and with a triarylphosphane P (aryl) 3, wherein X represents the anion of the acid HX and aryl is a substituted or unsubstituted C6-Ci4-aryl radical, via a cis-phenol of the formula Villa or VIIIb as an isolable intermediate,
  • R 3 is OH or R 2 , and R 2 and Y are as defined in formula VIa in step b),
  • Ci5-phosphonium salt of formula IX ' is also converted by partial hydrogenation of the triple bond in the cis-phosphonium salt of formula IX.
  • a secondary cis-alcohol of the formula VIIa or VIIb is subjected to the reaction conditions of the OH-protecting group elimination, in particular the acid-catalyzed acetal hydrolysis.
  • Strong organic or inorganic acids are understood as meaning those acids whose pK a values are less than 3, preferably less than 1.
  • Examples of strong organizational see or inorganic acids are hydrohalic acids, such as hydrochloric acid, hydrobromic acid or hydroiodic acid, sulfonic acids, such as methanesulfonic acid, p-toluenesulfonic acid or trifluoromethanesulfonic acid, or trihaloacetic acids, such as trifluoroacetic acid or trichloroacetic acid.
  • the aryl radicals are both substituted and unsubstituted C ⁇ -Cu, preferably C ⁇ -Cio-aryl radicals, in particular phenyl.
  • the substituents on the aryl radical can be, for example, halogens and / or C 1 -C 12, in particular C 1 -C 4 -alkyl radicals, such as methyl, ethyl, propyl or butyl.
  • triphenylphosphane is preferably used as the triarylphosphane P (aryl) 3.
  • Hydrobromic acid or hydrochloric acid and triphenylphosphine as triarylphosphane P (aryl) 3 are preferably used in process step d) in the reaction of the secondary cis-alcohol of the formula VIII or VIIIb to give the cis-phosphonium salt of the formula IX or IX '.
  • triarylphosphine-HX adducts of the formula P (aryl) 3 * HX in particular triphenylphosphine hydrochloride or triphenylphosphine hydrobromide used.
  • Y is -CH: CH - or -C ⁇ C-
  • R 2 for -O-CH (Me) -O-CH 2 CH 3 is reacted with triphenylphosphine hydrobromide to give a cis-phosphonium salt of the formula IX or IX '.
  • the Ci5 phenols of the formula VIIIa and VIIa-b run through, but need not be isolated in substance.
  • Aryl is phenyl and X is Br.
  • the intermediate of the formula VIIIa or VIIIb is not isolated, but the secondary cis-alcohol of the formula VIIa or VIIb directly to the cis Phosphonium salt of the formula IX or IX 'implemented.
  • the compounds of the formulas IVb, IVb ', Vb, VIb, VIIb, VIIIb, XI and IX' used or obtained in process steps a), b), c), d) and e) can be used as E isomer, Z, Isomer or E / Z isomer mixture present.
  • Preferred bases for the production of the ylid are alkali metal or alkaline earth metal C 1 -C 6 -alcoholates, preferably as a solution in the corresponding C 1 -C 6
  • chlorinated hydrocarbons such as methylene chloride, 1, 2-dichloroethane, 1, 2-dichloropropane or open-chain or cyclic ethers can be used.
  • ethereal solvents for example, tetrahydrofuran, dioxane or ethers of ethylene glycol can be used.
  • hydroxyl-containing ethers such as 1-methoxy-2-propanol or 1-methoxy-2-propanol
  • C 1 -C 6 -hydric alcohol corresponding to the alkoxide either alone or in combination t one of the above-mentioned solvents - suitable for this reaction.
  • Another preferred embodiment consists in the generation of the ylide by oxiranes as "latent bases" (Chem. Ber 107, 2050 ff, (1974)), for example by heating the C 15-phosphonium salt of the formula IX in the presence for several hours of the dialdehyde of the formula X in an oxirane as solvent, preferably 1,2-epoxybutane
  • This reaction can be carried out in pure oxirane or in mixtures of the oxirane with one of the abovementioned solvents
  • the end product of the formula I can be obtained by filtration of the reaction mixture without additional Work-up steps are isolated.
  • radicals R 1 and R 2 are defined as described above in step a), that is to say in which R 1 are identical or different, in particular identical and are a C 1 -C 8 -alkyl group, or the two radicals R 1 together represent a bicyclic C 2 -C 12 -alkylene radical, that is to say, together with the atoms which join them, form a cyclic ketal, in particular a 5- or 6-ring ketal, and R 2 represents an ether which can be converted into a hydroxy group by hydrolysis. , Silyl ether or acetal protecting group, and wherein the cis-building block of the formula IVb can be present as E-isomer, Z-isomer or E / Z isomer mixture.
  • radicals R 1 and R 2 are defined as described above in step a), that is to say in which R 1 are identical or different, in particular different and are a C 1 -C 8 -alkyl group or the two radicals R 1 together represent a divalent C 2 -C 12 -alkylene radical, that is to say, together with the atoms which join them, form a cyclic ketal, in particular a 5- or 6-ring ketal, and R 2 denotes an ether, silyl radical which can be converted into a hydroxy group by hydrolysis. ether or acetal protecting group, and wherein the cis-building block of formula IVb 'may be present as E-isomer, Z-isomer or E / Z isomer mixture.
  • Another object of the present invention is to provide a third object of the present invention.
  • Another object of the present invention is a secondary cis-alcohol of the formula VIIa or VIIb
  • Ci 5 phenol of the formula VIIIa or VIIIb is also the subject of the present invention.
  • R 3 is OH or R 2
  • R 2 and Y are as in formula VIIa
  • the Ci5-phenol of formula VIIIb may be present as E-isomer, Z-isomer or E / Z isomer mixture.
  • a cis-phenol of formula Villa wherein R 3 is OH or -O-CH (Me) -O-CH 2 CH 3 .
  • aryl and X are defined as previously described in step d), that is, wherein X is the anion of a strong organic or inorganic acid HX, and aryl is a substituted or unsubstituted C6-Ci4 aryl radical, and wherein the C15 phosphonium salt of the formula IX or IX 'can be present as E isomer, Z isomer or E / Z isomer mixture.
  • X is Cl or Br and aryl is phenyl.
  • Another object of the present invention is also a process for the preparation of a phosphonium salt of the formula IX
  • R 2 is an ether, silyl ether or acetal protecting group which can be converted by hydrolysis into a hydroxy group, and where the secondary cis-alcohol of the formula VIIb can be present as E-isomer, Z-isomer or E / Z isomer mixture, with a strong organic or inorganic acid HX and with a triarylphosphane P (aryl) 3, where X represents the anion of the acid HX and in particular represents Cl or Br, and aryl represents a substituted or unsubstituted C6-Ci 4 -aryl radical , in particular phenyl, stands,
  • Ci5-phosphonium salt is converted to a Ci5-phosphonium salt, wherein in the case of a starting material of the formula VIIa or VIIb, in which Y represents a triple bond, the triple bond of this cis-phosphonium salt is converted by partial hydrogenation in a double bond to the Ci5-phosphonium salt of the formula IX go, wherein the cis-phosphonium salt of formula IX may be present as E-isomer, Z-isomer or E / Z isomer mixture.
  • the organic phase was washed once with 1 l of saturated bicarbonate solution and twice with 1 l of water each time and dried with sodium sulfate. After filtering off the desiccant, the filtrate was concentrated on a rotary evaporator at 50 ° C to 20 mbar. 236.6 g of the cis building block of the formula Va-a (97.3% of theory) having a purity of 99.1% (gas chromatographic) were obtained as residue. For purification, the product was recrystallized from 500 ml of toluene.
  • the resulting suspension was cooled to 0 ° C, stirred for 1 hour at 0 ° C and the product was filtered off.
  • the filter cake was washed with a little cold acetonitrile and dried at + 50 ° C / 20 mbar.
  • the filtrate was concentrated on a rotary evaporator at + 50 ° C to 20 mbar.
  • the residue was taken up in 100 ml of acetonitrile.
  • the mixture was stirred for 15 min at +70 0 C, cooled to 0 ° C and stirred at 0 ° C for 1 hour.
  • the secondary crystals were filtered off, washed with a little cold acetonitrile and dried at + 50 ° C / 20 mbar.
  • 62.2 g of sodium bis (2-methoxyethoxy) aluminum dihydride (65% in toluene, diluted with 400 ml of toluene) were allowed to run in over the course of 1 hour.
  • the mixture was stirred for 2 hours at 0 ° C after.
  • a mixture of 33 ml of ethanol and 33 ml of n-hexane and then 33 ml of 15% sodium hydroxide solution were added dropwise at 0 ° C first.

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Abstract

L'invention concerne un nouveau procédé de production de 3,3'-dihydroxyisoréniératine de formule (I), ainsi que de nouveaux produits intermédiaires obtenus à partir du procédé.
PCT/EP2007/056794 2006-07-07 2007-07-05 Procédé de production de 3,3'-dihydroxyisoréniératine et ses nouveaux produits intermédiaires WO2008003737A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3468931A (en) * 1965-10-07 1969-09-23 Farmaceutici Italia 4'-substituted derivatives of 1,18-di(2',3',6'-trimethylphenyl-(1'))-3,7,12,16-tetramethyl-1,3,5,7,9,11,13,15,17-octadecanonaene
EP0005748A2 (fr) * 1978-06-02 1979-12-12 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Procédé de préparation de dérivés cyclohexéniques, ainsi que composés intermédiaires de synthèse
EP0101597A2 (fr) * 1982-08-20 1984-02-29 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Procédé pour la préparation de l'astaxanthine ainsi que les produits intermédiaires dans la synthèse de l'astaxanthine
EP0283979A2 (fr) * 1987-03-27 1988-09-28 F. Hoffmann-La Roche Ag Dérivés de l'éthinylcyclohexène
EP0882709A1 (fr) * 1997-06-04 1998-12-09 Basf Aktiengesellschaft Procédé pour la préparation de la zéaxanthine, intermédiaires pour ce procédé et procédé pour leur préparation
WO2007090095A2 (fr) * 2006-01-27 2007-08-09 Cardax Pharmaceuticals, Inc. Synthese d'analogues ou derives de carotenoides dotes de proprietes antioxydantes ameliorees

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3468931A (en) * 1965-10-07 1969-09-23 Farmaceutici Italia 4'-substituted derivatives of 1,18-di(2',3',6'-trimethylphenyl-(1'))-3,7,12,16-tetramethyl-1,3,5,7,9,11,13,15,17-octadecanonaene
DE1593440B1 (de) * 1965-10-07 1971-11-25 Farmaceutici Italia Substituierte 1,18-Di-[2',3',6'-trimethylphenyl-(1')]-3,7,12,16-tetramethyl-1,3,5,7,9,11,13,15,17-octadecanonaene und Verfahren zu ihrer Herstellung
EP0005748A2 (fr) * 1978-06-02 1979-12-12 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Procédé de préparation de dérivés cyclohexéniques, ainsi que composés intermédiaires de synthèse
EP0101597A2 (fr) * 1982-08-20 1984-02-29 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Procédé pour la préparation de l'astaxanthine ainsi que les produits intermédiaires dans la synthèse de l'astaxanthine
EP0283979A2 (fr) * 1987-03-27 1988-09-28 F. Hoffmann-La Roche Ag Dérivés de l'éthinylcyclohexène
EP0882709A1 (fr) * 1997-06-04 1998-12-09 Basf Aktiengesellschaft Procédé pour la préparation de la zéaxanthine, intermédiaires pour ce procédé et procédé pour leur préparation
WO2007090095A2 (fr) * 2006-01-27 2007-08-09 Cardax Pharmaceuticals, Inc. Synthese d'analogues ou derives de carotenoides dotes de proprietes antioxydantes ameliorees

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TUTORSKAYA, O. O. ET AL: "Regioselective synthesis of a 2,3,5-trimethyl-p-benzoquinone monoacetal and its reactions.", XP002454244, retrieved from STN Database accession no. 1990:611886 *
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TUTORSKAYA, O. O. ET AL: "Synthesis of 4-hydroxy-2,5-cyclohexadien-1-ones with isoprenoid substituents of varying structure", XP002454243, retrieved from STN Database accession no. 1992:173610 *
M. SOUKOUP ET AL: "Technical Procedures for the Syntheses of Carotenoids and Related Compounds from 6-Oxo-isophorone:Syntheses of (3R,3'R)-Zeaxanthin", HELVETICA CHIMICA ACTA, vol. 73, no. 4, 1990, pages 868 - 873, XP002453197 *
NOBUHISA OKUKADO ET AL: "SYNTHESIS OF PHENOLIC CAROTENOID,3,3'-DIHYDROXYISORENIERATENE", MEMOIRS OF THE FACULTY OF SCIENCE SER. C, vol. 9, no. 1, 1974, XP009090156 *
O.O. TUTORSKAYA ET AL: "Regioselective Synthesis of 2,3,5-Trimethyl-p-benzoquinone monoacetal and its transformations", J.ORG.CHEM. USSR (ENGL.TRANSL.), vol. 26, no. 5, 1990, pages 936 - 940, XP009090137 *
O.O.TUTORSKAYA ET AL: "Synthesis of 4-Hydroxy-2,5-cyclohexadien-1-ones with various isoprenoid substituents", J.ORG.CHEM.USSR (ENGL. TRANS.), vol. 27, no. 7, 1991, pages 1423 - 1428, XP009090136 *
WIDMER E: "SYNTHETIC ADVANCES IN THE CAROTENOID FIELD", PURE & APPLIED CHEMISTRY, vol. 57, no. 5, 1985, pages 741 - 752, XP001063958, ISSN: 0033-4545 *
ZHURNAL ORGANICHESKOI KHIMII , 26(5), 1087-91 CODEN: ZORKAE; ISSN: 0514-7492, 1990 *
ZHURNAL ORGANICHESKOI KHIMII , 27(7), 1423-8 CODEN: ZORKAE; ISSN: 0514-7492, 1991 *

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