Total synthesis of (3R,3'R,6'R)-lutein and its stereoisomers.
(3R,3'R,6'R)-lutein (1) is a major dietary carotenoid that is abundant in most fruits and vegetables commonly consumed in the U.S. and that accumulates in the human plasma, major organs, and ocular tissues. Numerous epidemiological and experimental studies have shown that 1 has important biological activities and may play an important role in the prevention of age-related macular degeneration (AMD). While the total synthesis of 1 has been previously reported in a poor overall yield, the total synthesis of the other seven stereoisomers of lutein has not yet been accomplished. We have developed a relatively straightforward methodology for the total synthesis of 1 and three of its stereoisomers, (3R,3'S,6'S)-lutein (2), (3R,3'S,6'R)-lutein or 3'-epilutein (3), and (3R,3'R,6'S)-lutein (4) by C(15) + C(10) + C(15) Wittig coupling reactions. Employing this methodology, the other four stereoisomers of lutein that are enantiomeric to the aforementioned lutein isomers can be similarly prepared. One of the important features of this strategy is its application to the total synthesis of (13)C-labeled luteins and their metabolites with appropriate stereochemistry for metabolic studies in animals and humans. This synthesis also provides access to the C(15)-precursors of optically active carotenoids with a 3-hydroxy-epsilon end group that are otherwise difficult to synthesize.
Khachik
Frederick
F
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA. khachik@umd.edu
Chang
An-Ni
AN
D000215:Acylation; D000447:Aldehydes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D055162:Biocatalysis; D002247:Carbon Isotopes / Q000737:chemistry; D002338:Carotenoids / Q000737:chemistry; D008049:Lipase / Q000737:chemistry / Q000378:metabolism; D014975:Lutein / Q000138:chemical synthesis* / Q000737:chemistry; D011551:Pseudomonas fluorescens / Q000201:enzymology; D013194:Staining and Labeling; D013237:Stereoisomerism
D000447:Aldehydes; D002247:Carbon Isotopes; D002338:Carotenoids; D008049:Lipase; C004984:apocarotenal; D014975:Lutein