Release of the Product from the Polymer Support under Neutral Conditions

Significance

A novel linker cleavable under neutral conditions was designed and synthesized. Polymer-supported dithymidine methyl phosphate 3 was prepared from thymidine phosphonate 2 and highly cross-linked polystyrene having 3-azidomethyl-4-hydroxybenzyl alcohol linker 1 (eq. 1). Dithymidine methyl phosphate 4 was then released from the polymer support by the reaction with MePPh₂ in aqueous dioxane (eq. 2). In this reaction, the azidomethyl group is converted into the aminomethyl group by a Staudinger reaction. Then, the intramolecular acyl migration to the resulting amino group gives amide 5 and product 4.