SYNTHESIS OF C-13-LABELED (ALL-E,3R,3'R)-BETA,BETA-CAROTENE-3,3'-DIOL(ZEAXANTHIN) AT C(12), C(13), C(12'), AND C(13') VIA L-E-2,7-DIMETHYLOCTA-2,4,6-TRIENE-1,8-DIAL-C-13(4)

The title compound (10) has been synthesized from all-E-2,7-dimethyloc ta-2,4,6-triene-1,8-dial (C-10-dialdehyde, 8) labelled with four C-13 from commercially available and relatively inexpensive starling materi als. The key starting material in this synthesis, (EtO)(2)P(O)(13)CHMe (13)CO(2)Et(2), has been prepared from triethyl phosphonoacetate-C-13( 2). The sodium salt of 2 reacted with fumarylaldehyde dimethylacetal t o give ethyl 6,6-dimethoxy-2-methyl-E,E-2,4-hexadienoate (4) which was converted to 8 in four steps [(1) acid hydrolysis, (2) 2/NaH, (3) LiA lH4 reduction, (4) MnO2 oxidation]. The overall yield of 8 based on ph osphonate 1 is 43-46%. The double Wittig reaction of 8 with hydroxy-be ta-ionylidene)ethyl]triphenylphosphonium chloride afforded 10, also kn own as (all-E,3R,3'R)-zeaxanthin-C-13(4) (39% based on phosphonate 1) in high purity. This synthetic method may be extended to prepare other C-13-labelled carotenoids.