Triplet-sensitized photooxygenation of therapeutic retinoids.

The triplet-sensitized photooxygenation of retinoic acid in hydroorganic buffer, methyl retinoate in a variety of solvents, and methyl 13-cis-retinoate and etretinate in ethanol has been investigated. By high-performance liquid chromatographic analysis, one major peroxide product was formed from each retinoid substrate under all conditions investigated. The structures of these peroxides have been assigned relying on high-field nuclear magnetic resonance and mass and ultraviolet spectroscopy. While product structures were not influenced, the rate of product formation was found to vary with solvent, substrate, and perhaps the nature of the sensitizer. The retinoid peroxides isolated are stable toward nucleophiles and weakly acidic and basic conditions. Possible reasons for rate variations in the photooxygenations are discussed.