P End Group

p-Carotene (3) is the most common representative of the carotenoids and was the first carotenoid to be synthesized. Three syntheses were reported nearly simultaneously [1-5] by different authors and, since then, many different approaches have been reported. p,p-Carotene (3) has been produced on a commercial basis since 1954 by Roche and since 1972 also by BASF, applying different processes. The technical syntheses will be treated in Chapters PartVn. The synthesis of p,P-carotene (3) on a laboratory scale is described in Worked Example 8. 

This is the end group of 3,4,3, 4 -tetradehydro-p,P-carotene (1) and 3,4-didehydro-p,p-carotene (2). The symmetrical molecule 1 was synthesized in an analogous way to p,p-carotene (3) via the Ci9 + C2 + Ci9 = C4o strategy [6]. For the synthesis of the Ci9-synthon, the ketone 19 was alkylated with lithium ethoxyacetylene (20) in liquid ammonia, followed by hydrogenation and hydrolysis to form the unsaturated Cn-aldehyde 27 which was elongated 

---

Derivative Solvent Molecular weight D. P. End-group assay on the methyl ether... 

Carotenoid absorbance extends from the UV to about 550 mn in the visible, as illustrated by the characteristic three-peaked spectrum of p-carotene shown in Fig. 9 below. The short wavelength peak in a carotenoid is usually attenuated if there is a P-end group present. In any event, the characteristic... 

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]. 

The most abundant carotenoid with the 3-hydroxy-5,6-epoxy-5,6-dihydro-p end group is violaxanthin (67), which is formed in large quantities in higher plants. 

The most important oarotenoid bearing 3-hydroxy-4-oxo-p-end groups is astaxanthin (83). All three stereoisomers, i.e. the (3S,3 S)-83 and (3R,3 R)-83 enantiomers, and the (3R,3 S)-mesoform [(3R,3 S)-83], have been isolated from natural sources the (3S,3 S)-isomer [(3S,3 S)-83] occurs most abundantly. A mixture of the three stereoisomers is produced on an industrial scale and is used mainly as a feed additive in aquaculture. 

The synthesis of fucoxanthin (121), reported by Ito is clearly a highlight in the field of carotenoid synthesis [32-74], The carotenoid was synthesized according to the strategy Cis + Cio + Ci5 = C40 with the Cio-dialdehyde 45 as central unit. As the allenic precursor 103 for the Ci5-end group 122 had previously been prepared for the synthesis of peridinin (108) the emphasis was on the preparation of the 3-hydroxy-8-oxo-p end group 123. 

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]. 

A representative of the Cso-carotenoids with a substituted p end group is C.p. 450 (203) which has been isolated from Corynebacterium poinsettiae. For the synthesis of that carotenoid in optically active form, the C2o + Cio + C2o = C5o strategy and the Wittig reaction were chosen [98]. 

At the 4th International Symposium on Carotenoids in Berne in 1975, the total synthesis of (3/, 3 / )-zeaxanthin (119) was reported by the Roche group. The 3-hydroxy-p end group is the most abundant chiral end group of the naturally occurring carotenoids almost 100... 

The acetylenic diol 1 has been used for the preparation of the phosphonium salts 9 (route 7 —and 10 (route 7 7772 70) which have been applied to the synthesis of p,p-carotene (3) [6]. The phosphonium salts 9 and 70 also proved their utility in the syntheses of 7,8-didehydroastaxanthin (402) and 7,8,7 ,8 -tetradehydroastaxanthin (400) [7] and of optically active carotenoids with 3,5,6-trihydroxy-5,6-dihydro-p-end groups [8]. Despite these interesting examples it is noteworthy that, in general, the diphosphonates are much better reagents for double olefination than the corresponding diphosphonium salts [9]. 

Two different approaches have been described for the synthesis of the 2-hydroxy-P end group in optically active form. The synthesis of (S)-p,p-caroten-2-ol (52) was performed via the reduction of 2-oxo-p-ionone (36) with baker s yeast, followed by acetylation to give (S)-2-acetoxy-p-ionone (43) in a yield of 60%. Subsequent conversion into (S)-p,p-caroten-2-ol (52) was achieved by standard procedures [12] (Scheme 10). 

Another efficient synthesis of optically active building blocks with the 3-hydroxy-p end group is achieved via asymmetric hydroboration. Reaction of the protected alcohol 69 with di-isopinocamphenylborane gave the diol 70, and selective oxidation of the allylic hydroxy group gave (Rj-3-hydroxy-p-cyclocitral (71) [21] (Scheme 15). 

A well-known carotenoid with the 4-hydroxy-p end group is isozeaxanthin (129) which has two chiral centres at C(4) and C(4 ) respectively. The mixture of the three stereoisomers can easily be prepared by reduction of canthaxanthin (380) with NaBH4. 

The 3,4-dihydroxy-P end group is best known in the tetrol crustaxanthin (197). Many partial syntheses starting with enantiomerically pure astaxanthin (406) have been described. In principle, different stereoisomers of crustaxanthin (197) can be obtained by reduction of 406 followed by chromatographic separation of the isomers, but this separation is demanding. 

Carotenoids with the 3-hydroxy-5,6-epoxy-5,6-dihydro-p end group... 

The reaction of the Ci5-phosphonium salt 170 with the C 10-dialdehyde 42 gave a mixture of 7,7-carotene (15) (yield 20%) and the C25-apocarotenal 173. The latter was then reacted, in a second Wittig reaction, with the Ci5-phosphonium salt 174 containing the P end group, to give p,7 carotene (5) in 15% yield. By use of racemic 7-ionone (171), partly resolved via its menthylhydrazone [52], the total synthesis of p,7-carotene (5) enriched in either the (6 R)- or the (6 S)-enantiomer was achieved later [53]. Recently a synthesis of both enantiomers of 7-ionone was developed [54]. 

---