The pivaloylglycol anchor group: A new platform for a photolabile linker in solid-phase synthesis

We have designed a new photolabile linker (2) based on 2-pivaloylglycerol f or the solid-phase synthesis of acids. The linker was prepared in six steps and anchored to the support via an amide bond. Photocleavage is a two-step process, in which the immobilized acids are released by photolytic generat ion of a radical center and subsequent spontaneous beta-C,O bond scission. The pivaloyl linker (2) was found to cleave with high yields and purities t he acids in various solvents (THF, CH2Cl2, dioxane, DMSO) by irradiation wi th light above 320 nm. Using this linker, we have demonstrated the solid-ph ase synthesis of test compounds by peptide synthesis, palladium-catalyzed c ross coupling, and epoxidation. The linker proved to be stable toward the t reatment with acids and bases. The photolysis rates of our pivaloyl Linker (2) were compared with the rates of a o-nitrobenzyl photolinker (1) and pro ved to be superior.