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United States Department of Agriculture

Agricultural Research Service

Title: Synthesis of 13c-Labelled (All-E,3r,3'r)-B,b-Carotene-3,3'-Diol (Zeaxanthin) at C(12), C(13), C(12'), C(13') Via All-E-2,7-Dimethylocta-2, 4,6-Triene-1,3-Dial-13c4

Authors
item Khachik, Frederick - CATHOLIC UNIVERSITY
item Beecher, Gary
item Li, Betty
item Englert, Gerhard - F. HOFFMAN-LA ROCHE LTD.

Submitted to: Journal of Organic Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 12, 1995
Publication Date: N/A

Interpretive Summary: Carotenoids are a class of food phytochemicals that have been extensively studied for their preventive effect against several cancers. Recently, oxidative metabolites of several prominent food and circulating carotenoids have been isolated and characterized in extracts of human plasma. Additional studies on the metabolism of carotenoids in human beings is hampered by the lack of non-radioactive materials and the dearth of technology to synthesize them. The current studies describe the model synthesis of a carotenoid (zeaxanthin) labelled with a stable isotope of carbon. The synthetic procedures described in this paper along with processes reported earlier for the synthesis of a labelled intermediate common to most carotenoids, permits the production of labelled carotenoids that can be used to investigate the metabolism of this important class of phytochemicals in humans. Companies specializing in the synthesis of labelled organic compounds and academic laboratories which support human metabolic units will utilize the results of the current research.

Technical Abstract: The title compound (10) has been synthesized from all-E-2,7- dimethylocta-2,4,6-triene-1,8-dial (C10-dialdehyde, 8) labelled with four (13)C from commercially available and relatively inexpensive starting materials. The key starting material in this synthesis, (EtO)2P(0)13CHMe13CO2Et (2), has been prepared from triethyl phosphonoacetate-13C2. The sodium salt of 2 reacted with fumarylaldehyde dimethylacetal to 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) LiAlH4 reduction, (4) MnO2 oxidation]. The overall yield of 8 based on phosphonate 2 is 57-60%. The double Wittig reaction of 8 with [(3R-3-hydroxy-beta-ionylidene)ethyl]triphenylphosphonium chloride afforded 10, also known as (all-E,3R,3'R)-zeaxanthin- 13C4 (50% based on phosphonate 2) in high purity. This synthetic method may be extended to prepare other 13C-labelled carotenoids.

Last Modified: 4/23/2014
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