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

An easy and efficient strategy to obtain libraries of 5'-phosphodiester and 5'-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 5'-phosphodiester linkage to Tentagel HL resin, functionalized with a 3-chloro-4-hydroxyphenylacetic linker. The solid phase synthesis of small libraries of 5'-phosphodiester and 5'-phosphoramidate monoester thymidine analogues is also reported.