The Claisen condensation route

An additional application of this method is seen in the synthesis [24] of wallemia A (75) which is the first natural pyrrol-2-ylpolyene P-diketone to be reported. In this Claisen condensation, freshly prepared lithium amide should be used to give successful results. 

The phenomenon of (E/Z)-isomerization (or cisitrans isomerization) in carotenoids has long been recognized. Interconversion of the (all- )- and various (mono-Z)- and (di-Z)-isomers occurs readily in solution, a process known to be catalysed by iodine in the presence of light [1]. Pure fZ)-isomers may be isolated by chromatography from such isomerization mixtures. The interest in pure (Z)-isomers of carotenoids has recently increased considerably [2,3], and the alternative preparation of (Z)-isomers by total synthesis has received growing attention. 

This Chapter deals with the total synthesis of specific (Z)-isomers of carotenoids by stereo-chemically controlled reactions. The preparation of fZj-isomers by (E/Zj-isomerization is not covered here. 

Historically, the first synthesis of (Z)-isomers of carotenoids became possible after the introduction of a special palladium catalyst (Lindlar catalyst) for the partial hydrogenation of carbon-carbon triple bonds [4]. Thus (15Z)-P,P-carotene [(15Z)-3] [5] and (11Z,1 l Z)-p,13-carotene [(11Z,1 rZ)-3] [6-8] were obtained as intermediates in the synthesis of the (all- 3 target carotene. This partial hydrogenation of triple bonds, proceeding stereospecifically as a syn addition, is still a valuable method for the synthesis of disubstituted double bonds in the (Z)-configuration. The various reactions used to form carbon-carbon double bonds in the construction of the carotenoid skeleton generally proceed with variable stereoselectivity and result in ( 7Z)-mixtures (Chapter 2 Parts I, HI and IV). 

When a total synthesis of a particular fZj-isomer of a carotenoid is being planned the thermodynamic stability of that isomer relative to the (all- )- and other (Zj-isomers must be considered in mind, because isomerization in solution inevitably occurs as a secondary event. 

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