+

WO1997031894A1 - Nouveau procede de preparation de pigments carotenoides - Google Patents

Nouveau procede de preparation de pigments carotenoides Download PDF

Info

Publication number
WO1997031894A1
WO1997031894A1 PCT/ES1997/000049 ES9700049W WO9731894A1 WO 1997031894 A1 WO1997031894 A1 WO 1997031894A1 ES 9700049 W ES9700049 W ES 9700049W WO 9731894 A1 WO9731894 A1 WO 9731894A1
Authority
WO
WIPO (PCT)
Prior art keywords
reaction
oxidation
carried out
procedure
organic medium
Prior art date
Application number
PCT/ES1997/000049
Other languages
English (en)
Spanish (es)
Inventor
Nuria Sanroma Virgili
Joan Carles Ferrater Martorell
Mildred De Bloos De Clercq
Juan A. Fernandez Martin
Original Assignee
Investigaciones Quimicas Y Farmaceuticas, S.A.
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 Investigaciones Quimicas Y Farmaceuticas, S.A. filed Critical Investigaciones Quimicas Y Farmaceuticas, S.A.
Priority to AU19271/97A priority Critical patent/AU1927197A/en
Priority to US08/945,385 priority patent/US5998678A/en
Publication of WO1997031894A1 publication Critical patent/WO1997031894A1/fr

Links

Classifications

    • 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
    • C07C403/24—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 six-membered non-aromatic rings, e.g. beta-carotene

Definitions

  • the objective is, as described below, to improve the pigmenting power of natural products, obtained by extractive processes, by chemical transformation of one of its components of general formula II (Scheme 2) in the compound of formula I (Scheme 1) Likewise, the chemical transformation of the compounds of general formula II is an objective of the present invention, when these do not come from a natural source, but are obtained by synthetic route
  • R and R are the same or different and can be H, lower acyl, fatty acyl or hydroxyl protecting group
  • lower acyl refers to an acyl group with a branched hydrocarbon chain or not of 2 to 5 Carbon atoms.
  • fatty acyl refers to an acyl moiety derived from a fatty acid.
  • the compounds object of the present invention are part of a wide family of compounds called Carotenoids, within which two large groups, hydrocarbons or CAROTEN and their oxygenated derivatives or XANTOFELAS are differentiated
  • the products described here are part of the latter group.
  • the carotenoids are made up of eight isoprenoid units linked in such a way that they are invested in the exact center of the molecule, since the two central methyl groups remain in relative position 1.6, while the other non-terminal methyl are in relative position 1 , 5 All carotenoids can be formally derived from a C40H56 acyclic structure, consisting of a long central chain of conjugated double bonds, to which it is subjected to hydrogenation, dehydrogenation, cyclization, oxidation, or a combination thereof.
  • Some carotenoids have biological activity as provitamins A, that is, they generate "in vivo", by an enzymatic process, the corresponding
  • Vitamin A This function is more common in those carotenes in which there is no substitution in the beta-ionone ring, and, as a consequence, they show greater structural similarity with vitamin A There are exceptions to this general rule, and thus, they have described certain carotene epoxides that have high activity as provitamins.
  • SUBSTITUTE SHEET (RULE 26) Carotenoids are widely distributed in nature, being responsible for the colors of fruits, flowers and even birds and marine animals. They are produced by a multitude of plants and microorganisms. However, animals, although they can metabolize them, are not able to synthesize them. Generally, they are mixed together, with one or the other predominant depending on the natural source from which they originate, the usual form of presentation being the corresponding fatty esters.
  • This carotenoid is the main constituent of the resin of marigold ⁇ Tagetes erecta L.), an extractive product that constitutes one of the most important natural sources of xanthophylls.
  • Marigold resin contains, together with Lutein, small amounts of other xanthophylls, mainly Zeaxanthin (I, Scheme 1).
  • the natural product has a high proportion of Lutein around 85-90% compared to a proportion of Zeaxanthin in the order of 4-5% of total xanthophylls
  • the final product should have the absolute configuration 3R, 3'S, or meso form, optically inactive, such as AG Andrewes confirmed in a paper published in Acta Chem. Scand. B, 137 (1974)
  • Zeaxanthin (3R, 3'S isomer) would present, for these cases, a pigmenting power even lower than that of natural Lutein itself, so that the isomerization process, instead of improving the dye, would make it worse
  • the resulting product I (Scheme 1) can be a stereoisomer or a mixture of two or more, with high pigmenting power.
  • Helv.Chim.Acta, 30, 266 (1947) describes the action of sodium in ethanol / benzene for the isomerization of alpha-carotene in beta-carotene and xanthophyll in zeaxanthin.
  • the Assays are carried out starting from quantities of the order of 30 mg of carotenoid, and the isolation and purification of the final products is carried out by chromatography In the same line, Andrewes et al in Acta Chem. Scand. B, 28, 137
  • SUBSTITUTE SHEET (RULE 26)
  • the development of the invention consists of three phases, the isomerization of the compounds of general formula II (Scheme 2) in the corresponding of formula I (Scheme 1), oxidation for the preparation of the compounds of general formula III (Scheme 3) and the subsequent reduction to the racemic mixture
  • the first phase of the process is based on the transformation of the compounds II (Scheme 2) into the corresponding compound I (Scheme 1) by action of a basic reagent in organic medium
  • the compounds of formula II include natural products, that is, obtained by extractive procedures, and those that have been prepared by chemical synthesis.
  • the reagent used in the isomerization process It is, as noted, of a basic nature. Sodium and potassium hydroxides and alkoxides, alkaline earth oxides, etc. must be considered included in this term. With all of them some conversion has been obtained, reaching in many cases values of 90% and higher
  • Temperature is a parameter of great importance in the development of the reaction. Excessive heating leads to the formation of a large number of thermal degradation products and, as a consequence, to a large decrease in the reaction performance. too low do not allow the evolution of the starting products It has been found that the most suitable range is between room temperature and 115 ° C, preferably between 65 and 90 ° C.
  • the temperature values define, in turn, the reaction time This is another critical parameter, since for a given temperature, excessively long times do not increase the degree of conversion, but favor the formation of many secondary products Reaction times They vary, depending on the conditions, between 5 minutes and 9 hours. Under optimal conditions times of the order of 30 min are enough to reach conversions of 80-90%
  • the final products are isolated and purified according to the usual methods. It should be noted that the high conversion achieved under the conditions described and the absence of significant amounts of impurities, together with the nature of the reagents and solvents used , allows to carry out the oxidation process without isolating the isomerized product.
  • the isomerization process entails their subsequent elimination by the usual methods.
  • the second phase of the dye preparation process consists in the oxidation of the hydroxyl groups of compound I (Scheme 1), obtained by isomerization, to obtain the corresponding keto groups (Scheme 3)
  • oxidation can be carried out on one of the hydroxyl groups or on both, depending on the reaction conditions.
  • the reagents used to carry out this process can be chosen from a wide variety of oxidants, such as salts, oxides and derivatives of Cr (VI), oxides and derivatives of manganese, DDQ, etc. . Good results have been obtained with chromium trioxide and its derivatives in neutral medium
  • the oxidation conditions must be extraordinarily mild. It is therefore important to carry out the oxidation reaction at low temperature, preferably between 0 and 15 ° C. Under these conditions reaction times of the order of 20min to 3 hours are sufficient to complete the oxidation. It is not advisable to prolong
  • the third, and last phase consists in the reduction of the corresponding oxidation product (III, Scheme 3), to obtain the racemic (I, Scheme 1)
  • reaction can be carried out on the isolated and purified product or on the oxidation crude without isolation or prior purification
  • the reduction has been carried out using different reagents, achieving the best results with hydrides, such as sodium or potassium borohydride or alkyl aluminum hydrides.
  • hydrides such as sodium or potassium borohydride or alkyl aluminum hydrides.
  • the times and conditions of the reduction have been defined by the nature of the solvent and the reagent used. Good results have been achieved with reaction times of the order of 30 min. using potassium borohydride as a reagent in a mixture of methanol / dichloromethane at 0 ° C
  • reaction conditions allow conversions of the order of 80-90% or higher to be achieved, simultaneously preventing the formation of degradation products, that is, the loss of total xanthophylls. Direct consequence is the possible direct use of the resulting product, without prior isolation or purification
  • SUBSTITUTE SHEET (RULE 26)
  • An aspect of extraordinary interest of the present invention is that the isomerization reaction can be carried out in an organic medium suitable as a food additive and, where appropriate, will not be affected by subsequent oxidation and reduction processes. Thus, and given the high conversion and purity obtained, it will be possible to use the isomerized product as an additive with hardly any subsequent manipulations.
  • the isomerization process entails a further improvement of the product characteristics.
  • This aspect represents an important improvement in the quality of the final product
  • An advantage, of extraordinary interest when working with extractive products, is that isomerization can be carried out directly on the natural products themselves without saponification or prior purification
  • the starting products, object of the present invention which are of natural origin, are usually present in the form of esters of fatty acids.
  • the treatment of these under the reaction conditions simultaneously produces saponification and the corresponding isomerization. , which is a great novelty compared to what has already been described.
  • SUBSTITUTE SHEET (RULE 26) The racemization of the final product is carried out, as described, in two phases, oxidation of the isomerized product and subsequent reduction
  • the final purification is carried out by the usual methods and, given the almost total absence of degradation products, it is simple.
  • SUBSTITUTE SHEET (RULE 26) 7.5 g of sodium methoxide is added at room temperature and under nitrogen atmosphere. Nitrogen is bubbled into the reaction mass for 10 min and, with strong stirring, the temperature is raised to 80 ° C. Under these conditions, stirring is maintained for 7 hours The solvent is cooled and evaporated in vacuo.
  • Example 1 The product of Example 1 is dissolved in 50 ml of dichloromethane The solution is cooled to 0 ° C and added with strong stirring
  • the solution is filtered and washed thoroughly with brine and with water. It is dried over sodium sulfate and filtered.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

Procédé de préparation de caroténoïde de formule générale (I) et des pigments qui contiennent ce composé en tant que composant de base. On l'obtient par réaction de composés d'origine naturelle ou synthétique ayant la formule générale (II), ou des extraits végétaux qui contiennent l'un de ces composés en tant qu'ingrédients de base, où R et R', identiques ou différents, représentent hydrogène, acyle inférieur, acyle gras ou un groupe protecteur d'hydroxyle, avec un réactif alcalin en milieu organique, oxydation et réduction ultérieure du produit résultant afin d'obtenir le mélange racémique.
PCT/ES1997/000049 1996-02-27 1997-02-25 Nouveau procede de preparation de pigments carotenoides WO1997031894A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU19271/97A AU1927197A (en) 1996-02-27 1997-02-25 New process for preparing carotenoid pigments
US08/945,385 US5998678A (en) 1997-02-25 1997-02-25 Process for preparing carotenoid pigments

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP9600521 1996-02-27
ES9600521A ES2107391B1 (es) 1996-02-27 1996-02-27 Procedimiento para la preparacion de carotenoides y pigmentos que los contienen.

Publications (1)

Publication Number Publication Date
WO1997031894A1 true WO1997031894A1 (fr) 1997-09-04

Family

ID=8294051

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/ES1997/000049 WO1997031894A1 (fr) 1996-02-27 1997-02-25 Nouveau procede de preparation de pigments carotenoides

Country Status (5)

Country Link
AU (1) AU1927197A (fr)
ES (1) ES2107391B1 (fr)
MX (1) MX9708181A (fr)
PE (1) PE19999A1 (fr)
WO (1) WO1997031894A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0834536A1 (fr) * 1996-10-04 1998-04-08 F. Hoffmann-La Roche Ag Isomérisation de xanthophylles
US5780693A (en) * 1996-10-04 1998-07-14 Roche Vitamins Inc. Process for the manufacturing of zeaxanthin from lutein
WO2002030769A1 (fr) * 2000-10-10 2002-04-18 Industrial Organica, S.A. De C.V. Procede d'obtention de 3'-epiluteine
US7015014B2 (en) 2000-01-27 2006-03-21 Dsm Ip Assets B.V. Isolation of carotenoid crystals
US8093436B2 (en) 2008-03-19 2012-01-10 University Of Maryland, College Park Process for synthesis of (3R,3′R)-zeaxanthin and (3R,3′S;meso)-zeaxanthin from (3R,3′R,6′R)-lutein via (3R)-3′,4′-anhydrolutein

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3879424A (en) * 1971-07-16 1975-04-22 Hoffmann La Roche Intermediate for the synthesis of zeaxanthins, xanthophylls, and 3-{62 -carotene
WO1996002594A2 (fr) * 1994-07-20 1996-02-01 Industrial Organica, S.A. De C.V. Procede d'isomerisation de la luteine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3879424A (en) * 1971-07-16 1975-04-22 Hoffmann La Roche Intermediate for the synthesis of zeaxanthins, xanthophylls, and 3-{62 -carotene
WO1996002594A2 (fr) * 1994-07-20 1996-02-01 Industrial Organica, S.A. De C.V. Procede d'isomerisation de la luteine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANDREWES, A. G.: "Isomerization of.epsilon.-carotene to.beta.-carotene and of lutein to zeaxanthin", ACTA CHEM. SCAND., SER. B (1974), 28(1), 137-8 CODEN: ACBOCV, 1974, XP002033437 *
P.KARRER ET AL: "Umwandlung von alpha-Carotin und von Xanthophyll in Zeaxanthin.", HELVETICA CHIMICA ACTA., vol. 30, no. 1, 1947, BASEL CH, pages 266 - 267, XP002033438 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0834536A1 (fr) * 1996-10-04 1998-04-08 F. Hoffmann-La Roche Ag Isomérisation de xanthophylles
US5780693A (en) * 1996-10-04 1998-07-14 Roche Vitamins Inc. Process for the manufacturing of zeaxanthin from lutein
US7015014B2 (en) 2000-01-27 2006-03-21 Dsm Ip Assets B.V. Isolation of carotenoid crystals
WO2002030769A1 (fr) * 2000-10-10 2002-04-18 Industrial Organica, S.A. De C.V. Procede d'obtention de 3'-epiluteine
US8093436B2 (en) 2008-03-19 2012-01-10 University Of Maryland, College Park Process for synthesis of (3R,3′R)-zeaxanthin and (3R,3′S;meso)-zeaxanthin from (3R,3′R,6′R)-lutein via (3R)-3′,4′-anhydrolutein

Also Published As

Publication number Publication date
MX9708181A (es) 1998-07-31
ES2107391A1 (es) 1997-11-16
ES2107391B1 (es) 1998-06-16
PE19999A1 (es) 1999-05-24
AU1927197A (en) 1997-09-16

Similar Documents

Publication Publication Date Title
US5780693A (en) Process for the manufacturing of zeaxanthin from lutein
US7485738B2 (en) Method for preparing high-content food-grade zeaxanthin
CA2544902C (fr) Procede d'isolation, de purification et de formulation d'une pate de luteine stable, de qualite commerciale a partir d'oleoresine
AU7243496A (en) A process for the formation, isolation and purification of comestible xanthophyll crystals from plants
US5998678A (en) Process for preparing carotenoid pigments
JP4266924B2 (ja) 新規ｔｒａｎｓ−ルテインに富むキサントフィルエステル濃縮物およびその調製方法
WO2000039221A1 (fr) Amelioration apportee a un procede pour produire des derives de pigments solubles, pouvant etre decomposes thermiquement
JP5794605B2 (ja) 植物源からカロテノイドを単離する方法
US20080051591A1 (en) Isolation and Purification of Carotenoids from Marigold Flowers
EP0733619A1 (fr) Procédé pour la préparation d'astaxanthine
EP2522655B1 (fr) Procédé de préparation de cristaux de xanthophylle de teneur supérieure en zéaxanthine d'oléorésine végétale
WO1997031894A1 (fr) Nouveau procede de preparation de pigments carotenoides
US9725411B2 (en) Process for a direct one-pot transformation of lutein to β-cryptoxanthin via its acetate ester
US20100121112A1 (en) Method for the purification of carotenoids from plant extracts and the products so obtained
US6420614B1 (en) Process for obtaining 3′-epilutein
US9162969B2 (en) Nitrooxyesters, their preparation and use
Khachik Transformation of naturally occurring (3R, 3′ R, 6′ R)-lutein and its fatty acid esters to (3 R)-β-cryptoxanthin and (3R, 6′ R)-α-cryptoxanthin
CA2544384C (fr) Processus de preparation d'alpha et de beta-cryptoxanthine
ES2223270B1 (es) Procedimiento para la sintesis de astaxantina.
Weedon Some recent advances in the synthesis of carotenoids
US2894003A (en) Benzonaphthofuranols
Yasuhara et al. The Synthesis of Tedanin and Its Isomer, 3-Hydroxy-2, 3-didehydro-β, φ-caroten-4-one
US962712A (en) Leuco diethylgallocyanin.
CN114044749A (zh) 一种二羟基玉米黄质二乙酸酯的制备方法及其应用
CN119948013A (zh) β-胡萝卜素合成(II)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU BR CA CN JP KR MX PL RU UA US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 08945385

Country of ref document: US

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 97530646

Format of ref document f/p: F

NENP Non-entry into the national phase

Ref country code: CA

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载