Ethyl P-apo-8’-carotenate

The reaction of the C20 ylide (45 a) with the unsymmetrical C10 dialdehyde, 2,6-dimethyl-2,4,6-octatriene-1,8-dial (49, R = H), shows a remarkable regioselectivity. Only one of the two aldehyde groups participates in a Wittig olefmation, leading uniformly to p-apo-8 -carotenal (48) 4 ). The Wittig reaction between the C20 ylide (45a) and ethyl-2,6-dimethyl-8-al-octatrienoate (49, R = OQHj) correspondingly yields an ethyl-p-apo-8 -carotenate (48, R = OC2H5)s8). 

The ester, ethyl p-apo-8 -carotenate (17 X = OEt) corresponding to p-apo-8 -carotenal is an important colourant which has been referred to earlier. Technically it has been derived from the Cjt compound, dehydro-p-CjT-carotenal, an intermediate in the synthesis of p-apo-8 -carotenal (Scheme 14b) by Wittig reaction with the phosphoran formed from the triphenylphosphonium salt of ethyl o-bromopropionate with sodium ethoxide (ref. 5,p459). The resultant dehydro compound was partially reduced with Lindlar catalyst and the product then themally isomerised to ethyl p-apo-8 -carotenate as shown in Scheme 17. 

In addition to p-carotene, canthaxanthin, p-apo-8 -carotenal and ethyl p-apo-8 -carotenate, the ketone citranaxanthin (C33), which occurs in certain citrus species, has been cited (ref. 57) as a compound produced on a manufacturing scale. It is obtained by the condensation of C30, p-apo-8 -carotenal with propanone in the presence of aqueous potassium hydroxide (Scheme 18). Its use does not appear to be applicable to the UK. 

Carotenoids are also present in animal products such as eggs, lobsters, greyflsh, and various types of hsh. In higher plants, they occur in photosynthetic tissues and choloroplasts where their color is masked by that of the more predominant green chlorophyll. The best known are P-carotene and lycopene but others are also used as food colorants a-carotene, y-carotene, bixin, norbixin, capsanthin, lycopene, and P-apo-8 -carotenal, the ethyl ester of P-apo-8-carotenic acid. These are Upid-soluble compounds, but the chemical industry manufactures water-dispersible preparations by formulating coUoid suspensions by emulsifying the carotenoids or by dispersing them in appropriate colloids. ... 

There are several provitamins A these belong to the carotenoid pigments. The most important one is P-carotene, and some of the pigments that can be derived from it are of practical importance. These are P-apo-8 -carotenal and P-apo-8 -carotenoic acid ethyl ester (Figure 9-2). Other provitamins are a- and y-carotene and cryptoxanthin. 

Fig. 3. Commercially important carotenoids P-carotene (10), canthaxanthin [514-78-3] (11), astaxanthin [472-61-7] (12), p-apo-8 -carotenal [1107-26-2] (13), p-apo-8 -carotenoic acid ethyl ester [1109-11-1] (14), and citranaxanthin [3604-90-8] (15).

Individual carotenoid compounds — P-carotene, P-apo-8 carotenal (Formula 9.10), apocarotenoic ethyl ester, and canthaxanthin (Formula 9.9) — are synthesized... 

Apart from the technical route described to p-apo-8 -carotenal, readily available vitamin A alcohol (Cjo) has served as an intermediate in the form of the phosphonium salt by reaction with the monodiethyl acetal of a Cio dial (ref. 54). The required Cjo monodiethylacetal was obtained (ref.5, p409) by the reaction of the mono aldehyde-protected derivative, the enol ether of methylmalonaldehyde, (C4) with the acetylenic Grignard reagent from trans 3-methyl-2-penten-4-yn-l-ol (C ) followed by acidic dehydration and partial reduction with Lindlar catalyst to give firstly 8-hydroxy-2,6-dimethylocta-2, 4,6-triene-l-al (Cio). Protection of the hydroxyl group by acetylation in pyridine solution with acetyl chloride and formation of the diethyl acetal with ethyl orthoformate followed by hydrolysis of the acetyl group and oxidation afforded the final CIO aldehyde component (D)shown in Scheme 15a. 

Synonyms Cl 40825 Ethyl ester of p-apo-8 -carotenic acid Ethyl ester of p-apo-8 -carotenic acid C30 Uses Colorant in foods P-Apo-8 -carotenic acid, methyl ester iNSieof... 

Ethyl ester of p-apo-8 -carotenic acid Ethyl ester of p-apo-8 -carotenic acid C30. See P-Apo-8 -carotenic acid, ethyl ester Ethyl ester of hydrolyzed animal protein (INCI) Ethyl ester of hydrolyzed collagen. See Hydrolyzed collagen, ethyl ester Ethyl ester of hydrolyzed keratin (INCI). See Ethyl hydrolyzed keratin Ethyl esW of hydrolyzed silk (INCI). See Hydrolyzed silk ethyl ester Ethyl ester of PVM/MA copolymer (INCI). See PVM/MA copolymer, ethyl ester N-Ethylethanamine. See Diethylamine Ethyl ethanoate. See Ethyl acetate Ethyl ether... 

P-Carotene (VII), canthaxanthin (XII), P apo-8 -carotenal (XIX) and the carboxylic acid ethyl ester derived from the latter are synthesized for use as colorants for edible fats and oils. These carotenoids, in combination with surface-active agents, are available as micro-emulsions (cf. 8.15.1) for... 

For analysis of carotenoids, 8 -apo-P-carotenal and C45-P-carotene (95), ethyl P-apo-8 -carotenoate and 3R-8 -apo-P-caroten-3,8 -diol (65), P-apo-lO -car-... 

Six main carotenoids are produced industrially by chemical synthesis (3-carotene, canthaxanthin, astaxanthin, p-apo-8 -carotenal, p-apo-8 -carotenoic ethyl ester, and citranaxanthin. The pigment is usually presented in microcrystalline form for its use in fatty foods, or microencapsulated as a hydrophilic colloid for use in aqueous media. 

As has been shown in previous Chapters the Wittig and the Horner-Emmons reactions are of utmost importance for the coupling of carotenoid end groups with the polyene chain. In the following example, the synthesis of the naturally occurring C25-apocarotenal 507 (12 -apo-P-caroten-12 -al, (3-apo-12 -carotenal) and also ethyl 8 -apo-P-caroten-8 -oate (1) (P-apo-8-carotenoic acid ethyl ester), which is produced industrially by means of these reactions, is described. 

The commercial apo-p-carotenoids ethyl 8 -apo-p-caroten-8 -oate (286) and 8 -apo-p-caroten-8 -al (287) may be prepared from the Cig-aldehyde 53, used in the synthesis of p,p-carotene (2). By reaction of 53 with the Cg-acetal 288 the C25-aldehyde 15,15 -didehydro-12 -apo-p-caroten-12 -al (289) is obtained [115], This compound can be transformed into the Cso-aldehyde 287 by consecutive enol ether condensations first with vinyl ethyl ether (17), to give the C2/-aldehyde 290, and then with prop-1-enyl ether (18), followed by partial hydrogenation and isomerization [116] Scheme 59... 

Ethyl 8 -apo-p-caroten-8 -oate (286) can be synthesized by Wittig olefination of 15,15 -didehydro-C27-aldehyde 290 with 291 [117] Scheme 60... 

The pioneering synthetic work quickly led to the synthesis of carotenoids on an industrial scale. The industrial production of p,p-carotene (3) began in 1954, only four years after its first synthesis on a laboratory scale. This extremely rapid development was made possible by the enthusiasm and perseverance of Isler and his colleagues at Roche in Basel. Since then, commercial synthesis of carotenoids has continuously advanced and today the two major industrial producers Roche and BASF produce six different carotenoids, namely p,p-carotene (3), canthaxanthin (380), optically inactive astaxanthin (403) and the apocarotenoids 8 -apo-p-caroten-8 -al (482), 8-apo-p-caroten-8 -oic acid (486) ethyl ester, and citranaxanthin (466). The total annual sale is now in the region of US 300 million, and the commercially produced carotenoids are used mainly as food and feed additives. 

Only six of the approximately 600 naturally occurring carotenoids [6] have so far been produced industrially these are three symmetrical C4o-carotenoids, p,p-carotene (3), cantha-xanthin (380), and astaxanthin (403), and three apo-p-carotenoids, ethyl 8 -apo-p-caroten-8 -oate (7), 8 -apo-p-caroten-8 -al (482) and the C33-ketone citranaxanthin (466). Table 1 gives the structural formulae of these pigments and their main applications. 

The three-step enol ether condensation is again used in the chain lengthening of 36 (Scheme 9) [22]. Coupling to vinyl ethyl ether (31) leads to the C27-aldehyde 44. Repetition of the reaction sequence with prop-l-enyl ethyl ether (28) yields the corresponding C30-aldehyde. After partial hydrogenation and thermal isomerization in petroleum ether, 8 -apo-P-caroten-8 -al (482) is obtained in a yield of approximately 50% based on 27. The conversion of 44 into ethyl 8 -apo-p-caroten-8 -oate (7) is described in Section C. 

Ethyl 8 -apo-P"Caroten-8 -oate (1) was synthesized at an early date by Wittig olefination of the 15,15 -didehydro-C27-aldehyde 44 with 1-carbethoxyethylidene triphenylphosphorane (62) (Scheme 18). The ylide can either be isolated for use as an intermediate or generated in situ from the phosphonium salt by reaction with sodium ethoxide. The reaction is preferably carried out in dichloromethane. Exchange of this solvent for ethanol yields the 15,15 -didehydro... 

Carotenoids act as antioxidants in solution, micelles, and liposomes (Hill et al. 1995, Mortensen and Skibsted 1997, Mortensen et al. 1997, Woodall et al. 1997). The scavenging ability of the carotenoids P-carotene, 8 -apo-P-caroten-8 -al, can-thaxanthin, 7 -apo-7 ,7 -dicyano-p-carotene, ethyl 8 -apo-P-caroten-8 -oate, and 7,7 -diapo-7,7 -di-phenylcarotene towards radical HOO correlated with their redox properties (Polyakov et al. 2001). 

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