Carotene epoxides

Britton, G. and Goodwin, T.W., Carotene epoxides from the Delta tomato mutant. Phytochemistry, 14, 2530, 1975. 

The interaction of carotenoids with cigarette smoke has become a subject of interest since the results of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group 1994 (ATBC) and CARET (Omenn et al. 1996) studies were released. P-Carotene has been hypothesized to promote lung carcinogenesis by acting as a prooxidant in the smoke-exposed lung. Thus, the autoxidation of P-carotene in the presence of cigarette smoke was studied in model systems (toluene) (Baker et al. 1999). The major product was identified as 4-nitro-P-carotene, but apocarotenals and P-carotene epoxides were also encountered. 

Kennedy, TA and Liebler, DC, 1991. Peroxyl radical oxidation of beta-carotene—Formation of beta-carotene epoxides. Chem Res Toxicol 4, 290-295. 

Fig. 3 Proposed reaction pathway of P-carotene prooxidant activity. P-C, P-carotene ROO% peroxyl radical ROO-P-C-, P-carotene radical R00-P-C-00% P-carotene peroxy radical P-CO, P-carotene epoxide RO% alkoxy radical. (Adapted in part from Ref. l)...

Wittig reaction between azafrinal [5,6-dihydroxy-5,6-dihydro-10 -apo-j8-caroten-lO -al (77)] and the Wittig compound (80) allowed the preparation of 5,6-dihydro-/3,/8-carotene-5,6-diol (78 9 E and 9 Z, IrS)." The pure d -trans diol had a very much lower polarity than other carotenediols, a property attributed to reduction in the extent of hydrogen-bonding due to steric hindrance. Treatment of (78) with Ph2S[OC(CF3)2Ph]2 yielded (55,6/ )-5,6-epoxy-5,6-dihydro-/3,/3-carotene (79). This is the first time that a carotene epoxide of known chirality has been prepared, and H and C n.m.r. and c.d. data are presented. 

It is assumed that in order to have vitamin A activity a molecule must have essentially one-half of its structure similar to that of (i-carotene with an added molecule of water at the end of the lateral polyene chain. Thus, P-carotene is a potent provitamin A to which 100% activity is assigned. An unsubstituted p ring with a Cii polyene chain is the minimum requirement for vitamin A activity. y-Car-otene, a-carotene, P-cryptoxanthin, a-cryptoxanthin, and P-carotene-5,6-epoxide aU have single unsubstimted rings. Recently it has been shown that astaxanthin can be converted to zeaxanthin in trout if the fish has sufficient vitamin A. Vitiated astaxanthin was converted to retinol in strips of duodenum or inverted sacks of trout intestines. Astaxanthin, canthaxanthin, and zeaxanthin can be converted to vitamin A and A2 in guppies. ... 

Carotene cleavage enzymes — Two pathways have been described for P-carotene conversion to vitamin A (central and eccentric cleavage pathways) and reviewed recently. The major pathway is the central cleavage catalyzed by a cytosolic enzyme, p-carotene 15,15-oxygenase (BCO EC 1.13.1.21 or EC 1.14.99.36), which cleaves p-carotene at its central double bond (15,15 ) to form retinal. Two enzymatic mechanisms have been proposed (1) a dioxygenase reaction (EC 1.13.11.21) that requires O2 and yields a dioxetane as an intermediate and (2) a monooxygenase reaction (EC 1.14.99.36) that requires two oxygen atoms from two different sources (O2 and H2O) and yields an epoxide as an intermediate. ... 

The speed of autoxidation was compared for different carotenoids in an aqueous model system in which the carotenoids were adsorbed onto a C-18 solid phase and exposed to a continnons flow of water saturated with oxygen at 30°C. Major products of P-carotene were identified as (Z)-isomers, 13-(Z), 9-(Z), and a di-(Z) isomer cleavage prodncts were P-apo-13-carotenone and p-apo-14 -carotenal, and also P-carotene 5,8-epoxide and P-carotene 5,8-endoperoxide. The degradation of all the carotenoids followed zero-order reaction kinetics with the following relative rates lycopene > P-cryptoxanthin > (E)-P-carotene > 9-(Z)-p-carotene. 

In the second oxidation method, a metalloporphyrin was used to catalyze the carotenoid oxidation by molecular oxygen. Our focus was on the experimental modeling of the eccentric cleavage of carotenoids. We used ruthenium porphyrins as models of cytochrome P450 enzymes for the oxidation studies on lycopene and P-carotene. Ruthenium tetraphenylporphyrin catalyzed lycopene oxidation by molecular oxygen, producing (Z)-isomers, epoxides, apo-lycopenals, and apo-lycopenones. 

A similar system, but with a more hindered porphyrin (tetramesitylporphyrin = tetraphenylporphyrin bearing three methyl substituents in ortho and para positions on each phenyl group), was tested for P-carotene oxidation by molecular oxygen. This system was chosen to slow the oxidation process and thus make it possible to identify possible intermediates by HPLC-DAD-MS analysis. The system yielded the same product families as with lycopene, i.e., (Z)-isomers, epoxides, and P-apo-carotenals, together with new products tentatively attributed to diapocarotene-dials and 5,6- and/or 5,8-epoxides of P-apo-carotenals. The oxidation mechanism appeared more complex in this set-up. 

The products formed after heating dried P-carotene at 180°C for 2 hr in a sealed ampoule (SI) with air circulation (S2) stirring with starch and water (S3) and during extrusion process (S4) were isolated. - In all systems, 5,6-epoxy-P-carotene (trans and two cis isomers), 5,8-epoxy-P-carotene (trans and four cis isomers), and 5,6,5,6-diepoxy-P-carotene were identified, along with 5,6,5,8-diepoxy-P-carotene in systems S3 and S4. Later on, along with the epoxides previously found, 5 P-apocarotenals with 20 to 30 carbons, P-caroten-4-one, and 6 different P-carotene cis isomers were isolated in systems S3 and S4, whereas lower numbers of degradation products were found in the other systems. ... 

Formation of oxidation products from 3-carotene, such as epoxides and apocarotenals, occurs only at extreme conditions of combined temperature, time, or pressure. 

The oxidation of P-carotene with potassium permanganate was described in a dichloromethane/ water reaction mixture (Rodriguez and Rodriguez-Amaya 2007). After 12 h, 20% of the carotenoid was still present. The products of the reaction were identified as apocarotenals (apo-8 - to apo-15-carotenal = retinal), semi-P-carotenone, monoepoxides, and hydroxy-p-carotene-5,8-epoxide. 

The HPLC analysis of milkweed, the food-plant source for Monarch butterflies, demonstrates that it contains a complex mixture of carotenoids including lutein, several other xanthophylls, xanthophyll epoxides, and (3-carotene, Figure 25.3b. There is a component in the leaf extract that is observed to elute near 8min, which has a typical carotenoid spectrum but is not identical to that of the lutein metabolite observed at near the same retention time in the extracts from larval tissue. 

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