Process for making metabolites of lycopene

Abstract

The invention is concerned with a multi-stage process for making an oxidative metabolite of the carotenoid lycopene, 2,6-cyclolycopene-1,5-diol having the formula ##STR1## In this process .alpha.-terpinyl acetate is oxidatively dihydroxylated to a cyclohexanediol (IV), the cyclohexanediol (IV) is oxidatively cleaved to a ketoaldehyde (V), the ketoaldehyde (V) is subjected to an intramolecular aldol condensation to give a cyclopentanol (VI), the cyclopentanol (VI) is silylated to its silylated derivative formylcylopentane (VII), the formylcyclopentane (VII) is subjected to a C.sub.3 -chain lengthening with acetone and simultaneously to a saponification for the cleavage of the acetyl group to give a cyclopentylbutenone (VIII), the cyclopentylbutenone (VIII) is reacted with vinyl magnesium bromide to give a pentadienol (IX), the pentadienol (IX) is converted with deprotection of the silylated hydroxy group into a phosphonium salt (X), this salt is subjected to a Wittig reaction with 2,7-dimethyl-2,4,6-octatriene-1,8-dial to give a tridecahexaenal (XII) and the tridecahexaenal (XII) is subjected to a Wittig reaction with a (3,7,11-trimethyl-dodeca-2,4,6,10-tetraenyl)triphenylphosphonium salt to give the desired 2,6-cyclolycopene-1,5-diol (II). A variant of this process, also in accordance with the invention, comprises converting the cyclopentylbutenone (VIII) into the phosphonium salt (X) via two alternative intermediates, namely a pentadienoic acid ester (XIV) and a different pentadienol (XV), into the same phosphonium salt (X). Moreover, the invention is concerned with the novel intermediates (V), (VI), (VII), (VIII), (IX), (X), (XII), (XIV) as well as (XV) and the individual process steps which lead to these novel intermediates. 2,6-cyclolycopene-1,5-diol is useful in the prevention of cancer growth in human cells.