An efficient solid phase synthesis of 5-phosphodiester and phosphoramidate monoester nucleoside analogues

An easy and efficient strategy to obtain libraries of 5ʹ-phosphodiester and 5ʹ-phosphoramidate monoester nucleoside analogues in a highly pure form has been developed, starting from a new nucleoside based solid support. The nucleoside scaffold has been anchored through a 5ʹ-phosphodiester linkage to Tentagel® HL resin, functionalized with a 3-chloro-4-hydroxyphenylacetic linker. The solid phase synthesis of small libraries of 5ʹ-phosphodiester and 5ʹ-phosphoramidate monoester thymidine analogues is also reported.