| Lutein is a dihydroxylated carotenoid present naturally in dark green leafy vegetables and a variety of fruit. It was shown to display powerful antioxidant properties and act as a high-energy blue light filter in the human eye. Studies showed a correlation between lutein intake and lower incidence in the development of Age-related Macular Degeneration (AMD), the leading cause of blindness in elderly individuals in the western world. Due to some enzymatic restrictions, humans lack the ability to synthesize lutein and must therefore absorb it through the diet or supplementation. A better understanding of lutein's in vivo metabolism would be extremely valuable in helping define the amounts required for an optimal protective effect and eye health. Previous studies dosing human subjects with minute dose of radiolabeled folate, beta-carotene or vitamin-E demonstrated the efficacy of this approach in obtaining such information.;In order to synthesize specifically labeled 14C-lutein, a novel chemo-enzymatic pathway was designed, following a C15+C10+C15=C40 route. A modified Julia coupling methodology was preferred over the traditionally used Wittig reaction. Extensive efforts were devoted to the optimization of the central C10 fragment, in such a way to select the best coupling partner in terms of time, cost and yield. Isozeaxanthin, a chiral structural isomer of lutein, was found to be a readily accessible and adequate model system to investigate and troubleshoot experimental conditions for the convergent coupling steps. |
