title: An efficient conversion of (3R,3'R,6'R)-lutein to (3R,3'S,6'R)-lutein (3'-epilutein) and (3R,3'R)-zeaxanthin.
abstract: Two dietary carotenoids, (3R,3'R,6'R)-lutein (1) and (3R,3'R)-zeaxanthin (2), and their metabolite (3R,3'S,6'R)-lutein (3'-epilutein) (3) accumulate in human serum, milk, and ocular tissues. There is increasing evidence that compounds 1 and 2 play an important role in the prevention of age-related macular degeneration. Therefore, the availability of these carotenoids for metabolic studies and clinical trials is essential. Compound 1 is isolated from extracts of marigold flowers (Tagete erecta) and is commercially available, whereas 2 is only accessible by a lengthy total synthesis, and a viable method for synthesis of 3 has not yet been developed. This report describes an efficient conversion of technical grade 1 to 2 via 3. Acid-catalyzed epimerization of 1 yields an equimolar mixture of diastereomers 1 and 3. The mixture was separated by enzyme-mediated acylation with lipase AK from Pseudomonas fluorescens that preferentially esterified 3 and after alkaline hydrolysis yielded this carotenoid in 90% diastereomeric excess (de). Compound 3 was also separated from 1 in 56-88% de by solvent extraction and low-temperature crystallization, Soxhlet extraction, or supercritical fluid extraction. Base-catalyzed isomerization of 3 gave 2 in excellent yield, providing a convenient alternative to the total synthesis of this important dietary carotenoid.
authors.affiliation: Department of Chemistry and Biochemistry, Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, Maryland 20742, USA. FK117@umail.umd.edu
authors.forename: Frederick
authors.initials: F
authors.lastname: Khachik
mesh_terms: D001711:Biotransformation; D002338:Carotenoids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D035264:Flowers; D006801:Humans; D008049:Lipase / Q000378:metabolism; D014975:Lutein / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D008268:Macular Degeneration / Q000517:prevention & control; D013058:Mass Spectrometry; D008895:Milk, Human / Q000737:chemistry; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D010949:Plasma / Q000737:chemistry; D011551:Pseudomonas fluorescens / Q000201:enzymology; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D031686:Tagetes / Q000737:chemistry*; D024341:Xanthophylls; D065146:Zeaxanthins; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C474265:(3R,3'S,6'R)-lutein; D024341:Xanthophylls; D065146:Zeaxanthins; D019207:beta Carotene; D002338:Carotenoids; D008049:Lipase; D014975:Lutein