Carotene cyclization

Carotenoids are a group of more than 750 naturally occurring molecules (Britton et al. 2004) of which about 50 occur in the normal human food chain. Of these, only 24 have, so far, been detected in human plasma and tissues (Khachik et al. 1995), with only six molecules being abundant in normal human plasma (for chemical formulas see Figure 13.1). Carotenoids are subdivided into two main classes the carotenes, cyclized (e.g., P-carotene) or uncyclized (e.g., lycopene) hydrocarbons, and the xanthophylls, which have hydroxyl groups (e.g., lutein and zeaxanthin), keto-groups (e.g., canthaxanthin), or both (e.g., astaxanthin) as functional groups. 

Beyer, R, Mayer, M., and Kleinig, K., Molecular oxygen and the state of geometric isomerism of intermediates are essential in the carotene desaturation and cyclization reactions in daffodil chromoplasts, Eur. J. Biochem. 184, 141, 1989. 

Beyer, R, Croncke, U., and Nievelstein, V., Biochemical aspects of carotene desaturation and cyclization in chromoplasts membranes from Narcissus pseudonarcissus. Pure Appl. Chem. 66, 1047, 1994. 

A series of desaturation reactions convert phytoene to i -carotene and then to lycopene, the important red pigment in tomatoes. In pepper, lycopene undergoes a cyclization reaction on both ends by lycopene P-cyclase, thus producing P-carotene (Fig. 8.2) [25]. Beta-carotene is then converted to -cryptoxanthin, zeaxanthin. 

The incorporation of " C-labelled neurosporene (138), lycopene, and y-carotene (141) into /3-carotene by cell extracts of Phycomyces blakesleeanus mutants has been demonstrated.Addition of unlabelled lycopene or /3-zeacarotene (140) caused approximately equal reduction of the incorpsration of [ C]neurosporene into /3-carotene, indicating that the alternative routes of Scheme 3 are of equivalent importance. The absolute configuration of C-6 of natural /3,y-carotene (55) is opposite to that of all C40 carotenoids with an e-ring end-group. " Opposite foldings of the aliphatic precursor are therefore required for cyclization to produce the y- and e-end-groups. 

Inhibitors have been used to investigate the biosynthesis of 1,2-dihydroneuro-sporene [l,2,7,8-tetrahydro-i/, i/f-carotene (143)] and related 1,2-dihydro-carotenoids in Rhodopseudomonas viridis, and possible alternative sequences are presented.The C-1,2 hydrogenation reaction is inhibited by CPTA [2-(4-chlorophenylthio)triethylammonium chloride], a compound known to inhibit cyclization and C-1,2-hydration in other systems, thus indicating possible similarity of the reactions involved. 

The cyclization was also successful with natural unsaturated aldehydes such as /J-carotene, c/s-retinal (95%), and trans-retinal (50%).183,1842 Compounds like 142 are potential intermediates in the syntheses of /J-carotene derivatives and polymeric alkenes.184,185,186... 

The carotenes and carotenoids are very important accessory pigments (Fig. 23-22). The major component in most green plants is (3-carotene. Green sulfur bacteria contain y-carotene in which one end of the molecule has not undergone cyclization and resembles lycopene (Fig. 22-5). Chloroplasts also contain a large variety of oxygenated carotenoids (xanthophylls). Of these, neoxanthin, violaxanthin... 

FIGURE 63.1 Starting with mevalonate, carotenoids are biosynthesized by a special branch of the terpenoid pathway. The first C-40 hydrocarbon unit formed is phytoene, a carotenoid with three conjugated double bonds, which then is enzymatically desaturated to successively yield (3-carotene, neurosporene, and lycopene. Other carotenoids such as (3-carotene and oxocarotenoids are produced from lycopene following cyclization and hydroxylation reactions. Thus, lycopene is a central molecule in the biosynthesis pathway of carotenoids. 

New Structures and Stereochemistry.—New Carotenoid Structures. A mutant strain of Rhizobium lupini contains a new nor-carotenoid, 2, 3 -trans-dihydroxy-2-nor-/3,/3-carotene-3,4-dione (1)." The wild-type R. lupini, when cultured in the presence of the cyclization inhibitors nicotine or CPTA, produced three new monocyclic carotenoids, 2,3-h-ans-dihydroxy-/3,-caroten-4-one (2), 3-hydroxy-/3,(/ -caroten-4-one (3), and p,tf/-carotene-2,3-trans-dio (4)," which were characterized by m.s. and n.m.r. The light absorption and mass spectra of a carotenoid from Rhodopseudomonas capsulata allowed its identification" as demethylspheroidenone [l-hydroxy-3,4-didehydro-l,2,7, 8 -tetrahydro- /f,(/f-caroten-2-one (5)]. 

Interest in the action of various chemicals on carotenoid biosynthesis has been maintained in Phycomyces blakesleeanus and its mutants, diphenylamine caused increased levels of phytoene and phytofluene and reduced levels of coloured carotenes, whereas dimethyl sulphoxide reduced both types.The drug AMO 1618 increased the levels of all types of carotenoids in all strains, probably by preventing cyclization of GGPP and so increasing the amount of this precursor available for dimerization. The Et2NCH2 group in the amines (106)—(108) was... 

The ionones and damascones are derived in nature from the degradation of carotenoids. Similarly, the related irones are formed by degradation of other higher terpenes. The ionones are synthesized from citral by aldol condensation with a ketone to form what are known as v /-ionones, which are then cyclized using an acid catalyst, as shown in Scheme 4.39. Some specific syntheses are shown later in Scheme 4.42, along with the syntheses of vitamin A and carotene. The ionones possess odours which are reminiscent of violet, sometimes also with woody notes. 

Two major groups of carotenoids are synthesized by higher plants carotenes, which are cyclized or uncyclized hydrocarbons, and xanthophylls, which are oxygenated derivatives of carotenes. 

The biosynthesis of carotenoids in plants has been reviewed extensively in recent years and is only briefly described here (Britton, 1988 Bartley and Scolnik, 1994 Sandmann, 1994). The committed step to carotenoid synthesis is the formation of the first compound phytoene by the head-to-head condensation of two molecules of GGDP by phytoene synthase. Phytoene is subjected to a series of four sequential desaturation reactions, by two separate enzymes to yield lycopene, which has eleven conjugated double bonds. Lycopene is then cyclized to /3-carotene by two /3-cyclizations or to a-carotene... 

Phytoene is desaturated to neurosporene or lycopene by the photosynthetic bacteria. These are then converted to carotenes by desaturation, saturation, cyclization and aromatization, and/or to... 

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