SYNTHESIS OF HIGH PURITY DMT-C3-DISULFIDE PHOSPHORAMIDITE

摘要

The 5' and 3'-thiol modified oligonucleotides are attractive tools with a vast number of potential applications in the field of nucleic acid chemistry. There is a strong interest in developing new disulfide compounds or to optimize synthesis of exisiting disulfide modifiers, which are efficient in generating the 3'- or 5'-end reactive thiol group. Various synthetic protocols have been employed to synthesize pure 3-((3-(bis(4-dimethoxytrityl)propyl)disulfanyl)propyl 2-cyanoethyl diisopropylphosphoramidite (compound 2) starting from 3-(dimethoxytrityl)propyl)disulfanyl)propan-l-ol, (compound 1). Herein, we describe an efficient, reproducible synthetic and purification protocol for target compound 2 from the compound 1. It is noteworthy that our reaction conditions were reproducible even at multi-gram scale (27 g) with a purity level as achieved in a small scale.