Applications of green chemistry in the manufacture of oligonucleotide drugs

We have modified the current phosphoramidite-based, solid-phase synthesis o f antisense oligonucleotides to accommodate principles of green chemistry. In this article, we summarize key accomplishments that reduce or eliminate the use or generation of toxic materials, solvents, and reagents. Also disc ussed are methodologies that allow reuse of valuable materials such as amid ites, solid-support, and protecting groups: thus improving the atom economy and cost-efficiency of oligonucleotide manufacture. Approaches to accident prevention and the use of safer reagents during oligonucleotide synthesis are also covered.