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 for 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 generation 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 the acids in various solvents (THF, CH2Cl2, dioxane, DMSO) by irradiation with light above 320 nm. Using this linker, we have demonstrated the solid-phase synthesis of test compounds by peptide synthesis, palladium-catalyzed cross coupling, and epoxidation. The linker proved to be stable toward the treatment with acids and bases. The photolysis rates of our pivaloyl Linker (2) were compared with the rates of a o-nitrobenzyl photolinker (1) and proved to be superior.