GB1585499A - Polyene compounds - Google Patents

Polyene compounds Download PDF

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GB1585499A
GB1585499A GB32189/77A GB3218977A GB1585499A GB 1585499 A GB1585499 A GB 1585499A GB 32189/77 A GB32189/77 A GB 32189/77A GB 3218977 A GB3218977 A GB 3218977A GB 1585499 A GB1585499 A GB 1585499A
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cyclopent
trimethyl
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pent
dioxo
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23GCOCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
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    • C07C35/00Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C35/02Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic
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    • C07C45/72Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C07C45/74Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
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    • C07C49/587Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/647Unsaturated compounds containing a keto groups being part of a ring having unsaturation outside the ring
    • C07C49/653Unsaturated compounds containing a keto groups being part of a ring having unsaturation outside the ring polycyclic
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    • C07C49/587Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/707Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups a keto group being part of a three- to five-membered ring
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    • C07C49/743Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups having unsaturation outside the rings, e.g. humulones, lupulones
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  • Polymers & Plastics (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
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Description

(54) POLYENE COMPOUNDS (71) We, F. HOFFMANN-LA ROCHE & CO., AKTIENGESELL SCHAFT, a Swiss Company of 124-184 Grenzacherstrasse, Basle, Switzerland, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention relates to polyene compounds. More particularly, the invention is concerned with novel carotenoid polyene compounds and a process for the manufacture of these compounds and of derivatives thereof.
The novel polyene compounds provided by the present invention have the following general formula
wherein R represents an oxo, acyloxy or hydroxy group and the broken lines denote optional carbon-carbon bonds.
The polyene compounds of the formula
which are embraced by formula I hereinbefore, are deep-red pigments which are suitable for the colouring of foodstuffs, pharmaceuticals and cosmetic preparations. They are also key substances for the manufacture of violerythrin and actinoerythrol.
Violerythrin [2,2'-dinor-astacene] has a deep blue colour which is surprising for a carotenoid. Violerythrin can be converted by reduction into the red actinoerythrol [2,2'-dinor-astaxanthin]. Moreover, actinioerythrol can be oxidised in solution to violerythrin by simply blowing air through the solution.
Violerythrin has hitherto been obtainable in large amounts only by oxidation of 2,2'-dinor-canthaxanthin. Violerythrin is now especially readily accessible from the novel polyene compounds of formula IA hereinbefore as shown in the following Formula Scheme:
o owv \ violerythrin i .Ji"i"i" r blu/ (Ib) \veow A' Acowe-a ^ ACO AcO 0 (Ic) 0 (Id) \ ,ÓAe \ o o < HO < gt OH HO (Ie) (If) I HO' & H ) OH & a :tinioerythrol o o ro o (Ig) \ o (Ih) (Ih) Wa L I , fviolerythrin The process provided by the present invention for the manufacture of the polyene compounds of formula IA comprises reacting a compound of the general formula
with a compound of the general formula
wherein R represents an oxo or acyloxy group, one of the symbols A and B repre sents the formyl group and the other symbol represents a triarylphosphonium methyl group of the formula H2-P [X] ,Y, in which X represents an aryl group and Y represents the anion of an organic or inorganic acid, and the broken line denotes an optional carbon-carbon bond, to give a polyene compound of the general formula
wherein R and the broken lines have the significance given earlier, and, if desired, converting the compound of formula I in which R represents an oxo group by partial hydrogenation into violerythrin, or converting a compound of formula I in which R represents an acyloxy group in optional sequence by partial hydrogenation and saponification into actinioerythrol or by partial hydrogenation, saponification and oxidation or saponification, oxidation and partial hydrogenation into violerythrin.
Of the aforementioned embodiments for the manufacture of the polyene compounds of formula IA there have been found to be especially convenient the procedures denoted as (a), (b), (c) and (d) hereinafter, namely the reaction of (a) a phosphonium salt of the general formula
wherein X and Y have the significance given earlier, or (b) a phosphonium salt of the general formula
wherein X and Y have the significance given earlier, or (c) a phosphonium salt of the general formula
wherein R' represents an acyloxy group and X and Y have the significance given earlier, or (d) a phosphonium salt of the general formula
wherein R', X and Y have the significance given earlier, with the dialdehyde of the formula
The starting materials are reacted with one another by means of a Wittig reaction in the presence of an acid-binding agent, for example an alkali metal hydroxide such as potassium hydroxide, an alkalii metal alcoholate such as sodium methyl ate or an alkylene oxide which may be alkyl-substituted, especially in the presence of ethylene oxide or 1,2-butylene oxide, if desired in a solvent, for example an alkanol such as isopropanol, a chlorinated hvdrocarbon such as methvlene chloride or dimethylformamide, at a temperature between room temperature and the boiling point of the reaction mixture.
An acyloxy group denoted by R or R' is derived from a lower or higher alkanecarboxylic acid or alkenecarboxylic acid. The lower members contain up to 6 carbon atoms and the higher members contain from 7 to 20 carbon atoms. Both members can be substituted by halogen, alkoxy or aryloxy. Examples of the lower members are the acetoxy, propionyloxy, butyryloxy, valeryloxy, caprylyloxy, monochloroacetoxy, dichloroacetoxy, ethoxyacetoxy and phenoxyacetoxy groups. Examples of the higher members are the palmitoyloxy, stearoyloxy and oleoyloxy groups.
The acyloxy groups substituted by halogen, alkoxy or aryloxy can be saponified to the hydroxy group without this being converted partially into the oxo group during the saponification.
When it is desired to convert a polyene compound of formula Ic or Id by the aforementioned procedures into actinioerythrol, then such polyene compounds must be substituted by one of the previously mentioned acyloxy groups which are readily cleavable by hydrolysis. When a normal ester of formula Ic or Id is used (e.g. the acetic acid or the palmitic acid ester), then the hydroxy group initially liberated during the saponification is converted immediately into the oxo group under the conditions required for the cleavage of the acyl groups, and violerythrin is obtained as the end nroduct.
Of the acyloxy groups which are cleavable under mild conditions there occupy a preferred position the acyloxy groups substituted by chloro or phenoxy, which can be saponified to the hydroxy group by means of weak alkalis at a temperature between about - 300C and + 500C. The monochloroacetoxy and dichloroacetoxv groups can even be hydrolysed by mere heating in water or in an aqueous alkanol. The (trichloro or trifluoro)acetoxy group is less suitable as the protecting group because of its liability.
The starting materials of the general formulae
wherein R', X, Y and the broken line have the significance given earlier, used in embodiments (a), (b), (c) and (d) of the process are novel. They can be prepared from a common key compound of the formula
which is likewise novel.
The preparation of the starting materials of formula IIAB starting from the triol of formula IX is illustrated in the following Formula Scheme in which X and Y have the significance given earlier:
The preparation of the starting materials of formula IICD starting from the triol of formula IX is illustrated in the following Formula Scheme in which R', X and Y have the significance given earlier:
The preparation of the starting materials of formula IIAB is carried out, in general, as follows: The triol of formula IX, 5 - [1,4 - dihydroxy - 2,5,5 - trimethyl - cyclopent - 2en - 1 - yl] - 3 - methyl - pent - 2 - en - 4 - yn - 1 - ol is first subjected to an allyl rearrangement to give the triol of formula X, 5 - [3,4 - dihydroxy - 2,5,5 - trimethylcyclopent - 1 - en - 1 - yl] - 3 - methyl - pent - 2 - en - 4 - yn - 1 - ol. The allyl rearrangement is conveniently carried out in an aqueous mineral acid such as sulphuric acid, if desired in the presence of a solvent such as acetone or tetrahydrofuran, or in an organic acid such as formic or acetic acid. If an organic acid is used, then the ester which intermediately results must be saponified (e.g. with an aqueous sodium carbonate solution).
The resulting triol of formula X is subsequently oxidised to the aldehyde of formula XI, 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 methyl - pent - 2 - en - 4 - yn - 1 - al. The oxidation can be carried out for example, using nickel peroxide or manganese dioxide. The oxidation is conveniently carried out in a solvent such as diethyl ether, ethyl acetate, dioxan or benzene, and at a temperature between - 30"C and the boiling point of the oxidation mixture.
The resulting acetylenic ketoaldehyde of formula XI is then either partially hydrogentaed to the olefinic ketoaldehyde of formula XII, 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - penta - 2,4 - dien - 1 - al, which is subsequently reduced to the olefinic ketoalcohol of formula XIV, 5 - [3,4 - dioxo2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - penta - 2,4 - dien - 1 - ol, or reduced to the acetylenic ketoalcohol of formula XIII, 5 - [3,4 - dioxo - 2,5,5trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - pent - 2 - en - 4 - yn - 1 - ol, which is subsequently partially hydrogenated to the olefinic ketoalcohol of formula XIV.
The partial hydrogenation of the ethynylcne to the vinylene group is carried out in a manner known per se using a partially deactivated palladium catalyst (Lindlar catalyst) in a solvent such as benzene, toluene, ethyl acetate or an alkanol such as methanol, conveniently at normal pressure and room temperature.
The conversion of the ketoaldehydes of formulae XI and XII into the ketoalcohols of formulae XIII and XIV is carried out using a reducing agent, for example sodium borohydride in ethanol, dimethylformamide, tetrahydrofuran or diethyleneglycol dimethyl ether, or sodium dihydro - bis(2 - methoxyethoxy)aluminate or diisobutylaluminium hydride in tetrahydrofuran or dimethyl ether, at a temperature below OOC, particularly at - 30"C.
The resulting ketoalcohols of formulae XIII and XIV are subsequently converted by treatment with a halogenating agent, for example phosphorus tribromide, phosphorus oxychloride, thionyl chloride or phosgene in an ether or in dimethylformamide or N-bromosuccinimide in the presence of dimethvlsulphide, into the correspnpding halides, which are converted by reaction with a triarylphosphine (e.g. triphenylphosphine) into the phosphonium salts of formulae IIa and llB which can be generically formulated under formula IIAB.
The preparation of the starting materials of formula IICD is carried out, in general, as follows: The triol of formula X obtained as previously described from the triol of formula IX by allyl rearrangement is oxidised to rhe aldehyde of formula XV, 5 - [3 - oxo - 4hydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - pent - 2 - en4 - yn - 1 - al. The oxidation is carried out in the same manner as previously described for the oxidation of the triol of formula X to the aldehyde of formula XI. As the oxidation agent there is, however, conveniently used 2,3 - dichloro - 5,6 - dicyano - benzoquinone since this guarantees the desired selectivity.
The resulting acetylenic hydroxyaldehyde of formula XV is either partially hydrogenated to the olefinic hydroxyaldehyde of formula XVI, 5 - (3 - oxo - 4hydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - penta - 2,4dien - 1 - al, which is subsequently esterified to an olefinic ester of formula XVIII, a 5 - [3 - oxo - 4 - acyloxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - ylJ - 3 - methyl- penta - 2,4 - dien - 1 - al, or esterified to an acetylenic ester of formula XVII, a 5 - [3 oxo - 4 - acyloxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - ylj - 3 - methyl - pent2 - en - 4 - yn - 1 - al which is subsequently partially hydrogenated if desired to the olefinic ester of formula XVIII.
The sequence in which the partial hydrogenation of the acetylenic compound and the masking of the hydroxy group is carried out is determined by the choice of the esterification agent. When there is used a halogenated carboxylic acid, the halogen atom of which could poison the catalyst, such as, for example, monochloroacetic acid or dichloroacetic acid, then it is recommended to initially partially hydrogenate the acetylenic hydroxyaldehyde of formula XV and subsequently to esterify the resulting olefinic hydroxyaldehyde of formula XVI. On the other hand, when there is used a halogen-free esterification agent, then the acetylenic hydroxyaldehyde of formula XV can initially be esterified and the resulting acetylenic ester of formula XVII can be subsequently partially hydrogenated.
The partial hydrogenation is carried out in an analogous manner to that previously described in detail.
The masking of the hydroxy group by esterification with a lower or higher alkanecarboxylic acid or alkenecarboxylic acid anhydride or halide, which may be substituted by halogen, alkoxy or aryloxy, is carried out, if desired in a solvent such as tetrahydrofuran or methylene chloride, in the presence of an organic nitrogen base such as pyridine or triethylamine at a temperature between about -300C and + 50 C.
The resulting masked ketoaldehydes of formulae XVII and XVIII are subsequently converted into the ester alcohols of formulae XIX and XX in the same manner as described earlier for the conversion of the ketoaldehydes of formulae XI and XII into the ketoalcohols of formulae XIII and XIV.
The resulting ester alcohols of formulae XIX and XX are subsequently converted, in the same manner as previously described in connection with the alcohols of formulae XIII and XIV, via the halides into the phosphonium salts of formulae IIC and IID which can be generically formulated under formula IICD.
The dialdehyde starting material of formula IIIA, 2,7 - dimethyl - octa - 2,6dien - 4 - yne - 1,8 - dial, is a known compound.
Likewise known is the analogous 2,7 - dimethyl - octa - 2,4,6 - trien - 1,8 - dial which, by reaction with a phosphonium sak of formula IIB directly yields violerythrin and by reaction with a phosphonium salt of formula IID directly yields actinioerythrol.
The aforementioned key compound of formula IX can be obtained, for example, from 2,5,5 - trimethyl - cyclopent - 2 - ene - 1,4 - dione of formula IV as shown in the following Formula Scheme:
The individual steps of this Formula Scheme are carried out, for example, as follows: The known 2,5,5 - trimethyl - cyclopent - 2 - en - 1,4 - dione of formula IV is dissolved in an organic solvent (e.g. an alkanol) and reduced at a temperature below 0 C with sodium borohydride. The desired 4 - hydroxy - 2,5,5 - trimethyl - cyclo pent - 2 - en - 1 - one of formula V is isolated by rectification from the isomers mixture which occurs during the working-up.
The 4 - hydroxy - 2,5,5 - trimethyl - cyclopent - 2 - en - 1 - one of formula V is an important compound in the preparation of the aforementioned key compound of formula IX. The 4 - hydroxy - 2,5,5 - trimethyl - cyclopent - 2 - en - 1 - one of formula V is novel and is the subject of our Divisional Application No. 8817/79 serial No. 1 585 500).
The hydroxy group of the hydroxyketone of formula V is subsequently masked by treatment with trimethylchlorosilane in the presence of an organic nitrogen (e.g. triethylamine) in diethyl ether in the cold at about OOC.
The resulting 2,5,5 - trimethyl - 4 - [(trimethylsilyl)oxy] - cyclopent - 2 - en1 - one of formula VI is then condensed in a solvent (e.g. tetrahydrofuran by means of a Grignard reaction with trimethyl - [(trans - 3 - methyl - pent - 2 - en - 4 - yn1 - yl)oxy] - silane of formula VII to give 5 - [2,5,5 - trimethyl - l - hydroxy - 4 [(trimethylsilyl)oxy] - cyclopent - 2 - en - 1 - yl] - 3 - methyl - 1 - [(trimethylsilyl)oxy] - pent - 2 - en - 4 - yne of formula VIII which, without isolation, is saponified by shaking with a dilute aqueous alkali hydroxide solution to give 5 - [1,4 - dihydroxy2,5,5 - trimethyl - cyclopent - 2 - en - 1 - yl] - trans - 3 - methyl - pent - 2 - en - 4yn - 1 - ol of formula IX.
The aforementioned trimethyl - [(trans - 3 - methyl - pent - 2 - en - 4 - yn - 4yl) - oxyj - silane of formula VII can be readily obtained by the action of trimethylchlorosilane at room temperature on trans - 3 - methyl - pent - 2 - en - 4 - yne in an ether such as dimethyl ether in the presence of an organic nitrogen base such as triethylamine.
The following Examples illustrate the present invention: Example 1.
After the addition of 150 ml of butylene oxide, 8.1 g of 5 - [3,4 - dioxo - 2,5,5trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - penta - 2,4 - diene - 1 - triphenylphosphonium bromide and 820 g of 2,7 - dimethyl - octa - 2,6 - dien - 4 - yn - 1,8dial are stirred at room temperature for 5 hours. The mixture is then introduced into water and extracted with methylene chloride. The extract is evaporated under reduced pressure. The residual 15,15' - didehydroviolerythrin is purified by adsorption on silica gel. U.V. maximum: 520 nm (in chloroform).
The resuking 15,15' - didehydroviolerythrin can be converted into violerythrin as follows: 5.6 g of 15,15' - didehydroviolerythrin are dissolved in 1000 ml of toluene. After the addition of 2 g of partially deactivated palladium catalyst (Lindlar catalyst), the solution is shaken in a hydrogen atmosphere at rooom temperature and normal pressure until the calculated amount of hydrogen has been taken up. The catalyst is then separated. The filtrate is evaporated under reduced pressure. The residual violerythrin melts at 2360-2380C after recrystallisation from methylene chloride/hexane. U.V.
maximum: 580 nm (in chloroform).
The 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methylpenta - 2,4 - diene - 1 - triphenylphosphonium bromide used as the starting material can be prepared as follows: 138 g of 2,5,5 - dimethyl - cyclopent - 2 - ene - 1,4 - dione are dissolved in 1000 ml of methanol. The solution is treated with 10 g of solid sodium borohydride while stirring at --20"C. After the reaction fades away, the mixture is introduced into a saturated aqueous sodium chloride solution and extracted with ethyl acetate. The extract is evaporated under reduced pressure. The residual crude 4 - hydroxy - 2,5,5trimethyl - cyclopent - 2 - en - 1 - one boils at 850-870C/0.S Torr after rectification.
97 g of 4 - hydroxy - 2,5,5 - trimethyl - cyclopent - 2 - en - 1 - one are dissolved in 600 ml of ether. After the addition of 90 ml of triethylamine, the solution is treated dropwise at OOC with 81 ml of trimethylchlorosilane and stirred at 0 C for 4 hours.
The mixture is then introduced into water and extracted with ether. The ether extract is washed with water, dried over sodium sulphate and evaporated under reduced pressure. The residual 2,5,5 - trimethyl - 4 - [(trimethylsilyl)oxyj - cyclopent - 2 - en1 - one boils at 400--43"C/0.02 Torr.
12.1 g of trimethyl - [(trans - 3 - methyl - pent - 2 - en - 4 - yn - 1 - yl)oxy]silane are dissolved in 150 ml of tetrahydrofuran. The solution is added dropwise to a Grignard solution prepared from 1.73 g of magnesium shavings and 7.78 g of ethyl bromide. The mixture is stirred for 1 hour and then, after the addition of a solution of 10.1 g of 2,5,5 - trimethyl - 4 - [(trimethylsilyl)oxy] - cyclopent - 2 - en - 1 - one in 50 ml of tetrahydrofuran, for a further 20 hours. The mixture is then introduced into a saturated aqueous ammonium chloride solution and extracted with ether. The extract is evaporated under reduced pressure. The residual 5 - [2,5,5 - trimethyl - 1 - hydroxy4 - [(trimethylsilyl)oxyj - cyclopent - 2 - en - 1 - ylj - 3 - methyl - 1 - [(trimethyl silyl)oxyj - pent - 2 - en - 4 - yne, a mixture of two isomers, is dissolved in 140 ml of methanol without purification and separation. After the addition of 28 ml of 5% aqueous potassium hydroxide, the solution is stirred for 5 minutes, subsequently introduced into a saturated aqueous sodium chloride solution and extracted with ether. The ether extract is evaporated under reduced pressure. The residual 5 - [1,4 - dihydroxy2,5,5 - trimethyl - cyclopent - 2 - en - 1 - ylj - trans - 3 - methyl - pent - 2 - en4 - 4 - yn - 1 - ol, a mixture of two isomers, is isomerised as follows without further purification: 90.4 g of 5 - [1,4 - dihydroxy - 2,5,5 - trimethyl - cyclopent - 2 - en - 1 - yl]trans - 3 - methyl - pent - 2 - en - 4 - yn - 1 - ol are dissolved in 1400 ml of methylene chloride. The solution is treated with 380 ml of 98% formic acid, stirred for 45 minutes and subsequently introduced into water. The organic phase is separated and evaporated under reduced pressure. The residue is taken up in 780 ml of methanol, treated with 200 g of potassium carbonate in 500 ml of water, stirred for 1 hour, introduced into water and extracted with ethyl acetate. The 5 - [3,4 - dihydroxy - 2,5,5trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - pent - 2 - en - 4 - yn - 1 - ol isolated from the extract melts at 121,-1220C.
2.35 g of 5 - [3,4 - dihydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yn - 1 - ol are dissolved in 200 ml of methylene chloride. After the addition of 90 g of activated manganese dioxide, the solution is stirred for 1 hour at room temperature. The mixture is then filtered. The filtrate is evaporated under reduced pressure. The residual 5 - [3,4 - dioxo - 2,5,5 - trimethylcyclopent - 1 - en - 1 - yl] - 3 - methyl - pent - 2 - en - 4 - yn - 1 - al melts at 1410--1420C after purification by adsorption on silica gel.
5 - [3 - Oxo - 4 - hydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - ylj - 3- methyl - pent - 2 - en - 4 - yn - 1 - al can be isolated as the byproduct.
4 g of 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yn - 1 - al are dissolved in 100 ml of ethyl acetate. The solution is shaken in a hydrogen atmosphere in the presence of 1 g of partially deactivated palladium catalyst (Lindlar catalyst) at room temperature and normal pressure until the calculated amount of hydrogen has been taken up. The catalyst is separated.
The filtrate is evaporated under reduced pressure. The residual 5 - [3,4 - dioxo2,5,5 - trimethyl - cyclopent - 1 - en - 1 - ylj - 3 - methyl - penta - 2,4 - dien - 1 - al is further processed as follows without purification.
4.64 g of 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - penta - 2,4 - dien - 1 - al are dissolved in 150 ml of tetrahydrofuran. The solution is treated dropwise at --70"C with 250 mg of sodium borohydride in 5 ml of water. After 20 minutes, the mixture is introduced into a saturated aqueous sodium chloride solution and extracted with ethyl acetate. The extract is evaporated under reduced pressure. The residual 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1en - 1 - yl] - 3 - methyl - penta - 2,4 - dien - 1 - ol is converted as follows into the desired phosphonium salt without further purification.
4.6 g of S - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - penta - 2,4 - dien - 1 - ol are dissolved in 20 ml of methylene chloride. The solution is added dropwise at 0 C to a suspension of 3.6 g of N-bromosuccinimide in 20 ml of methylene chloride and 2 ml of dimethylsulphide. The mixture is stirred at 0 C for 2 hours, then introduced into water and extracted with ether/hexane (2:1).
The crude 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methylpenta - 2,4 - diene - 1 - bromide remaining after evaporation of the extract is dissolved in 70 ml of ethyl acetate. The solution is treated with 5.3 g of triphenylphosphine. The 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - penta2,4 - diene - 1 - triphenylphosphonium bromide which separates in the course of 24 hours is dried in a high vacuum and then further processed as described in the first paragraph of this Example.
Example 2.
5.6 g of 5 - [3 - oxo - 4 -phenoxyacetyl - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 yl] - 3 - methyl - pent - 2 - en - 4 - yne - 1 - triphenylphosphonium bromide and 0.43 g of 2,7 - dimethyl - octa - 2,6 - dien - 4 - yne - 1,8 - dial are dissolved in 100 ml of isopropanol. After the addition of 4.1 ml of 2-N sodium methylate, the solution is stirred at room temperature for 1 hour. The mixture is then introduced into water and extracted with methylene chloride. The 2,2' - dinor - 7,7',8,8',15,15' - hexadehydroastaxanthin remaining after evaporation of the extract is purified by adsorption on silica gel. In the mass spectrum the compound shows the expected molecular weight of 562.
860 mg of 2,2' - dinor - 7,7',8,8',15,15' - hexadehydroastaxanthin are dissolved in 200 ml of toluene. After the addition of 300 mg of partially deactivated palladium catalyst (Lindlar catalyst), the mixture is hydrogenated in a hydrogen atmosphere at room temperature and normal pressure until the calculated amount of hydrogen has been taken up. The catalyst is then separated. The actinioerythrol [2,2' - dinorastaxanthin] remaining after evaporation of the filtrate melts at 207 208 C after recrystallisation from methylene chloride/hexane.
270 mg of 2,2' - dinor - 7,7',8,8',15,15' - hexadehydroastaxanthin are dissolved in 80 ml of toluene. After the addition of 0.7 g of solid sodium carbonate, air is blown through the solution until the greater portion of the starting material has been converted into 2,2' - dinor - 7,7',8,8',15,15' - hexadehydroastacene. The mixture is filtered.
The crude product remaining after evaporation of the filtrate is purified by adsorption on silica gel. The mass spectrum shows a molecular weight of 558. The pure 2,2'dinor - 7,7',8,8',15,15' - hexadehydroastacene can be converted into violerythrin [2,2'dinor - astacene] in the same manner as described for the hydrogenation of 2,2' - dinor 7,7',8,8',15,15' - hexahydroastaxanthin to actinioerythrol.
The 5 - [3 - oxo - 4 - phenoxyacetyl - 2,5,5 - trimethyl - cyclopent - 1 - en - 1yl] - 3 - methyl - pent - 2 - en - 4 - yne - 1 - triphenylphosphonium bromide used as the starting material can be prepared as follows: 50 g of the 5 - [3,4 - dihydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl]3 - methyl - pent - 2 - en - 4 - yn - 1 - ol obtained according to Example 1 are dissolved in 300 ml of dioxan. After the addition of 120 g of 2,3 - dichloro - 5,6 - dicyano - benzoquinone, the solution is stirred at 800C for 5 hours. The mixture is then cooled. The 2,3 - dichloro - 5,6 - dicyano - benzohydroquinone which separates as the byproduct is filtered off. The 5 - [3 - oxo - 4 - hydroxy - 2,5,5 - trimethyl - cyclopent1 - en - 1 - yl] - 3 - methyl - pent - 2 - en - 4 - yn - 1 - al, an oil, which remains after evaporation of the filtrate is purified by adsorption on silica gel and is further processed as follows: 34 g of 5 - [3 - oxo - 4 - hydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl]3 - methyl - pent - 2 - en - 4 - yn - 1 - al are dissolved in 400 ml of ether. After the addition of 15 ml of pyridine, the solution is treated dropwise at -200C with 30 g of phenoxyacetic acid chloride. After 30 minutes, the mixture is introduced into water and extracted with ether. The 5 - [3 - oxo - 4 - phenoxyacetyl - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - pent - 2 - en - 4 - which remains after evaporation of the extract shows a U.V. maximum at 487 nm (in chloroform).
1 g of 15,15' - didehydroactinioerythrol dicaetate is dissolved in 200 ml of toluene.
The solution is treated, with the complete exclusion of air, with an equivalent amount of 2-N sodium methylate until the control by thin-layer chromatography indicates the end of the reaction. The mixture is introduced into water. The organic phase is separated and evaporated. The residual 15,15' - didehydroactinioerythrol contaminated by 15,15' - didehydroviolerythrin can be purified by adsorption on silica gel.
420 mg of the resulting crude 15,15' - didehydroactinioerythrol are dissolved in 100 ml of toluene. After the addition of 1 g of solid sodium carbonate, air is blown through the solution until the greater portion of the starting material has been converted into 15,15' - didehydroviolerythrin. The mixture is filtered. The 15,15' - didehydroviolerythrin which remains after evaporation of the filtrate is purified by adsorption on silica gel. The mass spectrum shows a molecular weight of 562. U.V. maximum: 520 nm (in chloroform).
The resulting 15,15' - didehydroviolerythrin can be partially hydrogenated to violerythrin as described in Example 1.
The 15,15' - didehydroactinioerythrol previously obtained can be partially hydrogenated to actinioerythrol as follows: 1.2 g of 15,15' - didehydroactinioerythrol are dissolved in 280 ml of toluene. After the addition of 0.8 g of partially deactivated paladium catalyst (Lindlar catalyst), the solution is hydrogenated in a hydrogen atmosphere at room temperature and normal pressure until the calculated amount of hydrogen has been taken up. The catalyst is then separated. The actinioerythrol which remains after evaporation of the filtrate melts at 207 208 C after recrystallisation from methylene chloride/hexane.
In the same manner as previously described, 15,15' - didehydroactinioerythrol diacetate can be hydrogenated to actinioerythrol diacetate; U.V. maximum: 518 nm (in chloroform).
The 5 - [3 - oxo - 4 - acetyl - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 3 - methyl - penta - 2,4 - diene - 1 - triphenylphosphonium bromide used as the starting material can be prepared as follows: 1 g of the 5 - [3 - oxo - 4 - hydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1yl] - 3 - methyl - pent - 2 - en - 4 - yn - 1 - al obtained according to Example 2 is dissolved in 250 ml of ethyl acetate. After the addition of 5 g of partially deactivated palladium catalyst (Lindlar catalyst), the solution is hydrogenated at room temperature and normal pressure with the addition of 0.24 ml of quinoline until the calculated amount of hydrogen has been taken up. The catalyst is separated. The 5 - [3 - oxo4 - hydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - penta - 2,4dien - 1 - al which remains after evaporation of the filtrate is processed as follows without further purification: 55 g of 5 - [3 - oxo - 4 - hydroxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl]3 - methyl - penta - 2,4 - dien - 1 - all are dissolved in 700 ml of ether. After the addition of 100 ml of pyridine, the solution is treated dropwise at - 200C with 25 ml of acetyl chloride. After 30 minutes, the mixture is introduced into water and extracted with ether. The practically pure, oily 5 - [3 - oxo - 4 - acetoxy - 2,5,5 - trimethylcyclopent - 1 - en - 1 - yl] - 3 - methyl - penta - 2,4 - dien - 1 - al which remains after evaporation of the extract is further processed as follows: 10 g of 5 - [3 - oxo - 4 - acetoxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl]3 - methyl - penta - 2,4 - dien - 1 - ali are dissolved in 200 ml of tetrahydrofuran and 10 ml of water. 1.5 g of sodium borohydride are introduced portionwise into the solution at --45"C. After 30 minutes, the mixture is introduced into a saturated aqueous sodium chloride solution and extracted with ether. The practically pure, oily 5 - [3oxo - 4 - acetoxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - pent2,4 - dien - 1 - ol [I.R. spectrum: 3550 cm-l and 1730 cm-1] which remains after evaporation of the extract is converted into the desired phosphonium salt as follows: 7.35 g of 5 - [3 - oxo - 4 - acetoxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 yl] - 3 - methyl - penta - 2,4 - dien - 1 - ol are dissolved in 20 ml of methylene chloride. The solution is introduced into a suspension of 9 g of N-bromosuccinimide in 15 ml of methylene chloride and 5 ml of dimethylsulphide. The mixture is stirred at room temperature for 1 hour, then introduced into water and extracted with ether. The crude 5 - [3 - oxo - 4 - acetoxy - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - penta - 2,4 - diene - 1 - bromide which remains after evaporation of the extract is dissolved in 100 ml of ethyl acetate. The solution is treated with 7 g of triphenylphosphine. The 5 - [3 - oxo - 4 - acetoxy - 2,5,5 - trimethyl - cyclopent - 1 en - 1 - yl] - 3 - methyl - penta - 2,4 - diene - 1 - triphenylphosphonium bromine which separates in crystalline form in the course of 24 hours melts at 212--215"C.
Example 4.
7.4 g of 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yne - 1 - triphenylphosphonium bromide are stirred at room temperature for 3 hours together with 0.9 g of 2,7 - dimethyl - octa - 2,6 - dien - 4yne - 1,8 - dial in 100 ml of butylene oxide. The mixture is subsequently evaporated.
The residual 2,2' - dinor - 7,7',8,8',15,15' - hexadehydroastacene [7,7',8,8',15,15'- hexadehydroviolerythrin] can be converted by partial hydrogenation into violerythrin as described in Example 2.
The 5 - 13,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methylpent - 2 - en - 4 - yne - 1 - triphenylphosphonium bromide used as the starting material can be prepared as follows: 5.7 g of the 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yn - 1 - al obtained according to Example 1 are dissolved in 100 ml of tetrahydrofuran. The solution is treated at - 700C while stirring with 260 mg of sodium borohydride in 5 ml of water. After 30 minutes, the mixture is introduced into a saturated aqueous sodium chlonde solution and extracted with ethyl acetate. The 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yn - 1 - ol which remains after evaporation of the extract is processed as follows without further purification: 2.3 g of 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yn - 1 - ol are dissolved in 20 ml of methylene chloride.
The solution is added dropwise at O"C to a suspension of 2 g of N-bromosuccinimide in 20 ml of methylene chloride and 3 ml of dimethylsulphide. After 2 hours, the mixture is introduced into water and extracted with ether/hexane (2:1). The crude 5- [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - mtehyl - pent - 2en - 4 - yne - 1 - bromide which remains after evaporation of the extract is dissolved in 100 ml of ethyl acetate. The solution is treated with 2.6 g of triphenylphosphine.
The sticky, oil 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yne - 1 - triphenylphosphonium bromide is dried in a high vacuum after separation of the supernatant solvent. Infrared spectrum: 1755 cml; 1696 cm1.
The following Example illustrates the production of a colouring preparation containing a polyene compound obtained according to the present invention: Example A.
Production of a colouring preparation suitable for the colouring of foodstuffs: 1.0 g of 15,15' - didehydroviolerythrin, 0.1 g of d,l - xr - tocopherol. 0.4 g of arachis oil and 1.0 g of ascorbyl palmitate are dissolved in 50 ml of hot chloroform.
The solution is homogenised with 4.1 g of gelatin, 1.7 g of sugar, 1.7 g of yellow dextrin and 0.2 g of sodium carbonate - dissolved in 50 ml of water. The homogenate is poured on to a metal sheet, dried chloroform-free in a vacuum and pulverised.
1-50 g of the previously obtained colouring preparation are required for the colouring of 100 kg of candy mass. The colouring preparation, dissolved in 10-500 ml of warm water, is added to the candy mass together with the aromas (e.g. red-currant or raspberry aroma) and the resulting mixture is homogeneously mixed.
WHAT WE CLAIM IS: 1. A process for the manufacture of polyene compounds, which process comprises reacting a compound of the general formula
with a compound of the general formula
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (18)

**WARNING** start of CLMS field may overlap end of DESC **. en - 1 - yl] - 3 - methyl - penta - 2,4 - diene - 1 - triphenylphosphonium bromine which separates in crystalline form in the course of 24 hours melts at 212--215"C. Example 4. 7.4 g of 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yne - 1 - triphenylphosphonium bromide are stirred at room temperature for 3 hours together with 0.9 g of 2,7 - dimethyl - octa - 2,6 - dien - 4yne - 1,8 - dial in 100 ml of butylene oxide. The mixture is subsequently evaporated. The residual 2,2' - dinor - 7,7',8,8',15,15' - hexadehydroastacene [7,7',8,8',15,15'- hexadehydroviolerythrin] can be converted by partial hydrogenation into violerythrin as described in Example 2. The 5 - 13,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methylpent - 2 - en - 4 - yne - 1 - triphenylphosphonium bromide used as the starting material can be prepared as follows: 5.7 g of the 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yn - 1 - al obtained according to Example 1 are dissolved in 100 ml of tetrahydrofuran. The solution is treated at - 700C while stirring with 260 mg of sodium borohydride in 5 ml of water. After 30 minutes, the mixture is introduced into a saturated aqueous sodium chlonde solution and extracted with ethyl acetate. The 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yn - 1 - ol which remains after evaporation of the extract is processed as follows without further purification: 2.3 g of 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yn - 1 - ol are dissolved in 20 ml of methylene chloride. The solution is added dropwise at O"C to a suspension of 2 g of N-bromosuccinimide in 20 ml of methylene chloride and 3 ml of dimethylsulphide. After 2 hours, the mixture is introduced into water and extracted with ether/hexane (2:1). The crude 5- [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - mtehyl - pent - 2en - 4 - yne - 1 - bromide which remains after evaporation of the extract is dissolved in 100 ml of ethyl acetate. The solution is treated with 2.6 g of triphenylphosphine. The sticky, oil 5 - [3,4 - dioxo - 2,5,5 - trimethyl - cyclopent - 1 - en - 1 - yl] - 3methyl - pent - 2 - en - 4 - yne - 1 - triphenylphosphonium bromide is dried in a high vacuum after separation of the supernatant solvent. Infrared spectrum: 1755 cml; 1696 cm1. The following Example illustrates the production of a colouring preparation containing a polyene compound obtained according to the present invention: Example A. Production of a colouring preparation suitable for the colouring of foodstuffs: 1.0 g of 15,15' - didehydroviolerythrin, 0.1 g of d,l - xr - tocopherol. 0.4 g of arachis oil and 1.0 g of ascorbyl palmitate are dissolved in 50 ml of hot chloroform. The solution is homogenised with 4.1 g of gelatin, 1.7 g of sugar, 1.7 g of yellow dextrin and 0.2 g of sodium carbonate - dissolved in 50 ml of water. The homogenate is poured on to a metal sheet, dried chloroform-free in a vacuum and pulverised. 1-50 g of the previously obtained colouring preparation are required for the colouring of 100 kg of candy mass. The colouring preparation, dissolved in 10-500 ml of warm water, is added to the candy mass together with the aromas (e.g. red-currant or raspberry aroma) and the resulting mixture is homogeneously mixed. WHAT WE CLAIM IS:
1. A process for the manufacture of polyene compounds, which process comprises reacting a compound of the general formula
with a compound of the general formula
wherein R represents an oxo or acyloxy group, one of the symbols A and B repre sents the formyl group and the other symbol represents a triarylphosphonium methyl group of the formula --CH,,-P[X]3r=, in which X represents an aryl group and Y represents the anion of an organic or inorganic acid, and the broken line denotes an optional carbon-carbon bond, to give a polyene compound of the general formula
wherein R and the broken lines have the significance given earlier in this claim, and, if desired, converting the compound of formula I in which R represents an oxo group by partial hydrogenation into violerythrin, or converting a compound of formula I in which R represents an acyloxy group in optional sequence by partial hydrogenation and saponification into actinioerythrol, or by partial hydrogenation, saponification and oxidation or saponification, oxidation and partial hydrogenation into violerythrin.
2. A process according to claim 1, wherein a phosphonium salt of the general formula
wherein X and Y have the significance given in claim 1, is reacted with the dialdehyde of the formula
3. A process according to claim 1, wherein a phosphonium salt of the general formula
wherein X and Y have the significance given in claim 1, is reacted with the dialdehyde of the formula
4. A process according to claim 1, wherein a phosphonium salt of the general formula
wherein R' represents an acyloxy group and X and Y have the significance given in claim 1, is reacted with the dialdehyde of the formula
5. A process according to claim 1, wherein a phosphonium salt of the general formula
wherein R' represents an acyloxy group and X and Y have the significance given in claim 1, is reacted with the dialdehyde of the formula
6. A process according to claim 2, wherein a 5 - [3,4 - dioxo - 2,5,5 - trimethyl cyclopent - 1 - en - 1 - yl] - methyl - pent - 2 - en - 4 - yne - 1 - triphenylphosphonium halide is reacted with 2,7 - dimethyl - octa - 2,6 - dien - 4 - yne - 18 - dial.
7. A process according to claim 3, wherein a 5 - [3,4 - dioxo - 2,5,5 - trimethyl cyclopent - 1 - en - 1 - yl] - 3 - methyl - penta - 2,4 - diene - 1 - triphenylphosphonium halide is reacted with 2,7 - dimethyl - octa - 2,6 - dien - 4 - yne - 1,8 - dial.
8. A process according to claim 4, wherein a 5 - [3 - oxo - 4 - (acyloxy) - 2,5,5trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - pent - 2 - en - 4 - yne - 1 - triphenylphosphonium halide is reacted with 2,7 - dimethyl - octa - 2,6 - dien - 4 - yne1,8 - dial.
9. A process acording to claim 5, wherein a 5 - [3 - oxo - 4 - (acyloxy) - 2,5,5trimethyl - cyclopent - 1 - en - 1 - yl] - 3 - methyl - penta - 2,4 - diene - 1 - tri phenylphosphonium halide is reacted with 2,7 - dimethyl - octa - 2,6 - dien - 4 - yne1,8 - dial.
10. A process for the manufacture of polyene compounds, substantially as hereinbefore described with reference to any one of Examples 1 to 4.
11. A polyene compound, when manufactured by the process claimed in any one of claims 1 to 10 inclusive or by an obvious chemical equivalent thereof.
12. Polyene compounds of the general formula
wherein Rl represents an oxo, acyloxy or hydroxy group and the broken lines denote optical carbon-carbon bonds.
13. 2,2' - Dinor - 7,7',8,8',15,15' - hexadehydro - astacene. (Ia).
14, 2,2 - Dinor - 15,15' - didehydro - astacene. (Ib).
15. 2,2' - Dinor - 7,7',8,8',15,15' - hexadehydroastaxanthin diacetate. (Ic).
16. 2,2' - Dinor - 15,15' - didehydroastaxanthin diacetate. (Id).
17. 2,2' - Dinor - 7,7',8,8',15,15' - hexadehydroastaxanthin. (Ie).
18. 2,2' - Dinor - 15,15' - didehydroastaxanthin. (If).
GB32189/77A 1976-08-02 1977-08-01 Polyene compounds Expired GB1585499A (en)

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