P,e-carotene

Traditionally, carotenoids have been given trivial names derived usually from the biological source from which they are isolated, but a semisystematic scheme has been devised that allows carotenoids to be named unambiguously and in a way that defines and describes their structure (Table 7.2). Specific names are based on the stem name carotene preceded by the Greek-letter prefixes that designate the two end groups. For example, 3-carotene is correctly referred to as p, p-carotene, and a-carotene as p, e-carotene. 

In contrast to the unsubstituted p end group, the e end group possesses an asymmetric carbon atom at position 6 and therefore, in the synthesis of compounds with this end group, the stereochemistry has to be considered. The most prominent carotene with the 8 end group is p,e-carotene (a-carotene) (127) which possesses the (6 R)-configuration. By analogy with the synthesis of p,p-carotene (2), the strategy Ci6 + Ca + Ci6 = C40 was used for the first synthesis of a-carotene (127) [75-77]. 

In 1957 a new era began with the synthesis of chiral carotenoids in optically active form, the first example being the naturally occurring (6 R)-p,e-carotene (7) and its enantiomer by the school of Karrer. The strategy used involved the resolution of the enantiomers of the end group synthon by separation of the diastereoisomeric menthylhydrazones. 

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. 

As an example of the Shapiro reaction, the 2,4,6-triisopropylphenylsulphonylhydrazone of (-)-(3/ )-3-hydroxy-P-ionone (34) is treated with an excess of -BuLi in hexane in the presence of TMEDA to give the vinyllithium reagent 35 which, on condensation with the C27-aldehyde 36, furnishes the C4o-allylic alcohol 37 in 75% yield, en route to (3/ ,6 / )-P,E-carotene-3,19-diol [20] (Scheme 9). 

By use of the enantiomeric (( )S)- and ((+)-R)-a-ionones ((S)- and (R)-79), the naturally occurring (6 / )-P,e-carotene (7) and its enantiomer have been synthesized. This constituted the first synthesis of an optically active carotenoid [46]. The enantiomers of a-ionone (79) were obtained by resolution of the racemate via the menthylhydrazones [47]. Recently an improved route to the enantiomerically pure a-ionones ((S)- and (R)-79) on a preparative scale has been developed [48]. The procedure, which is based on the separation of diastereoisomers, is described in the Worked Example 7. 

Synonyms p,e-Carotene-3,3 -diol Lutein Vegetable lutein Vegetable luteol... 

The chirality of lutein (14) is now firmly established with the 3,3 -hydroxy functions in the P- and s-rings possessing opposite absolute configuration 4, 40). The stereochemistry of the hydroxylation step in zeaxanthin (26) biosynthesis in a Flavobacterium sp. has been determined by using (5/ )-[2- C, 5- Hi] mevalonate as substrate which demonstrated retention of the 5-pro-S hydrogen at C-3(3 ) (50), Scheme 9. Also in the case of lutein (14) it has been shown that the 5-pro-S hydrogen at C-3 is retained (81,171) and P,e-carotene (92) biosynthesized from (4/ )-[2- C, 4- Hi] mevalonate retains the tritium at C-6 (82). Any mechanistic interpretation of the biosynthetic evidence must be consistent with the established chirality. 

Buchecker, R., C. H. Eugster, H. Kj0sen, and S. Liaaen-Jensen Absolute configuration of p,e-caroten-2-ol, p,p-caroten-2-ol and p,p-carotene-2,2 -diol. Acta Chem. Scand. B28, 449 (1974). 

P, e-caroten-3 -one) were extracted from plasma and separated on a nitrile column (A = 325nm and 495 nm) using a 74.62/20.00/0.25/0.10 hexane/dichloro-methane/methanol/diisopropylamine mobile phase [674]. A table of absorbance maxima is given for the analytes in the mobile phase. (The nonpolar carotenoids all eluted in the first 10 min and were successfully separated in a reversed-phase method described Chapter 9.) Elution of the polar carotenoids was complete in <30 min. Good peak shapes were generated. 

Epoxy-5,6-dihydro-p,e-carotene-3,3 -diol, 9CI. Xanthophyll epoxide. Lutein epoxide [28368-08-3]... 

Fig. 7.35 Structures, numbering, trivial names, and systematic names in brackets) of major carotenes Greek letters at the terminal residues are identical with those of the systematic names. The systematic name for a-carotene (structure not shown) is (6 i )-P,e-carotene...

---