Carotenoids inactive

Zeinoxanthin (3/ ,6 / )-/3,e-Caroten-3-ol Bicyclic, monohydroxy-carotenoid Inactive... 

Fertile sources of carotenoids include carrots and leafy green vegetables such as spinach. Tomatoes contain significant amounts of the red carotenoid, lycopene. Although lycopene has no vitamin A activity, it is a particularly efficient antioxidant (see Antioxidants). Oxidation of carotenoids to biologically inactive xanthophyUs represents an important degradation pathway for these compounds (56). 

Clearly, the control of gene expression at the transcriptional level is a key regulatory mechanism controlling carotenogenesis in vivo. However, post-transcriptional regulation of carotenoid biosynthesis enzymes has been found in chromoplasts of the daffodil. The enzymes phytoene synthase (PSY) and phytoene desaturase (PDS) are inactive in the soluble fraction of the plastid, but are active when membrane-bound (Al-Babili et al, 1996 Schledz et al, 1996). The presence of inactive proteins indicates that a post-translational regulation mechanism is present and is linked to the redox state of the membrane-bound electron acceptors. In addition, substrate specificity of the P- and e-lycopene cyclases may control the proportions of the p, P and P, e carotenoids in plants (Cunningham et al, 1996). 

Foss BJ, Sliwka HR, Partali V, Kopsel C, Mayer B, Martin HD, Zsila F, Bikadi Z, and Simonyi M. 2005b. Optically active oligomer units in aggregates of a highly unsaturated, optically inactive carotenoid phospholipid. Chemistry-A European Journal 11(14) 4103—4108. 

Further work using time-resolved EPR and magnetophotoselection (MPS), using plane-polarized light to excite the triplet state, gave information on the orientation of the optical transition dipole axes relative to the principal axes of the triplet state. By this technique the transition moments of the primary donor"6, the carotenoid in the bRC"7 and the bacteriopheophytin in the inactive B branch 4>0"8 were determined. 

From a nutritional viewpoint, the carotenoids are classified as provitamins and inactive carotenoids. To have vitamin A activity, the carotenoid molecule must incorporate a molecule of retinol, i.e., an unsubstituted /3-ionone ring with an 11-carbon polyene chain. /3-carotene (C40H56, MW = 536.88), the most ubiquitous provitamin A carotenoid, is composed of two molecules of retinol joined tail to tail thus the compound possesses maximal (100%) vitamin A activity. The structures of all other provitamin A carotenoids incorporate one molecule of retinol and hence theoretically contribute 50% of the biological activity of /3-carotene. Among the 600 or so carotenoids that exist in nature, only about 50 possess vitamin A activity in varying degrees of potency. 

By comparing the drug uptake by the MDR gene-transfected mouse lymphoma cells in the presence of some selected carotenoids, the carotenoids were classified into three different groups based on MDR reversal activity inactive, moderately active and very active. As shown in Table 1, the... 

Much less inhibition was found in the MCF7/MDR1 drug-resistant human breast cancer cell line in the presence of same carotenoids as were investigated earlier on the human MDR1 gene-transfected mouse lymphoma cells. As Table 5 shows the, rhodamine accumulation was enhanced only moderately from 1.1 to 2.2 fluorescence activity ratio, which means that the rhodamine uptake was enhanced from 10% to 120% in the human breast cancer cells. On the other hand, some carotenoids such as Zl-neoxanthin, mono-epoxy-a-carotene and 15,15-dehydro-diepoxy-/J-carotene were inactive (Table 5). 

Other Commissions on Nomenclature of the lUPAC have not been inactive. In biochemistry reports have been made on steroids (II), amino acids (12), vitamins (8), and carotenoids (7). A report on the nomenclature of macro-molecular compounds has been approved (6). 

The 3-hydroxy-p end group is the most abundant chiral end group in carotenoids and is often called the zeaxanthin end group. Zeaxanthin (55) possesses two chiral centres at C(3) and C(3 ), making possible three optical isomers, namely the (3R,3 R)-isomer (most abundant in Nature) and the (3S,3 S)-isomer as well as the (3R,3 S)-isomer which constitutes a meso-form. It is this optically inactive mixture of isomers which is usually obtained by synthesis of the so-called racemate [50]. 

Removal of a p-nitro group from peroxidative diphenyl ethers drastically reduced their peroxidative activity while increasing the inhibition of carotenoid biosynthesis, provided a substituted formamide substituent is present in the metaposition (1, Fig. 4.1.3). Both the o- and p-derivatives are inactive (reviewed in Ref [27]). Lipophilicity of the phenoxy ring and chain length of the alkyl group up to five carbon atoms increases activity, while branching results in a loss of activity. QSAR equations of the effect of the carbonamide substituent have been calculated [38]. No commercial product has been developed. 

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. 

The Roche group extended this work and in 1981, at the 6th International Symposium on Carotenoids in Liverpool, reported the total synthesis of several of the ten optical isomers of e,8-carotene-3,3 -diol (tunaxanthin, 149) and of four diastereoisomers of p,e-carotene-3,3-diol, including the most common (3R,3 / ,6 / )-isomer, lutein (133). The starting material for these syntheses was 6-oxoisophorone, which the Roche scientists went on to use to synthesize a large number of dicyclic carotenoids in optically inactive and active form, as reported at the 7th International Symposium on Carotenoids in Munich in 1984. 

The (9Z)> and (9Z,9 Z)-isomers of acetylenic carotenoids have been prepared by synthesis. The total synthesis of the (9Z,9 Z)-isomer of optically inactive alloxanthin (117) [12,13] has been treated in detail in Chapter 3 Part IV, as has the synthesis of (9Z)-mytiloxanthin (353) [33,34]. The (9Z)- and (9Z,9 Z)-isomers, respectively, of 402 and 400, the mono- and diacetylenic analogues of (3.5,3 5)-astaxanthin, have been synthesized [14], and recently also the (9Z)-isomers of (3/ ,3 / )-diatoxanthin (118) and (3/ )-7,8-didehydro-p,p-caroten-3-ol [35]. All these syntheses are based on an acetylenic C 5-phosphonium salt, as discussed in Section C.4, where the Wittig condensation with an appropriate aldehyde leads to stereoselective formation of the thermodynamically stable (9Z)-isomer. 

Phytoene has been incorporated into carotenoids in several cell-free systems (Kushwaha et al., 1970, 1976 Subbarayanet al., 1970 Davies, 1973 Brown et al., 1975), and its position as an intermediate in the biosynthesis of more unsaturated carotenes is now well accepted. Previously some workers had concluded that phytoene did not behave as a precursor of carotenoids (for a review, see Britton, 1976a). This conclusion appears to have resulted from the accumulation of a metabolically inactive pool of phytoene in studies with inhibitors, and a failure of phytoene in this pool to be converted under certain conditions to carotenes on removal of the inhibitor. 

No allenic carotenoids have yet been prepared by total synthesis, but the allenic ketones (55) and (56) have been synthesized as racemates (92). In a recent preliminary note the total synthesis of optically inactive 2,6-trans-2, 6 -trans decaprenoxanthin has been outlined. Natural deca-prenoxanthin (8) has 2/ ,6R,2 R,6 7 -configuration (11) with the 2,6(2, 6 )-substituents in a cis relationship. 

---