Applications of green chemistry in the manufacture of oligonucleotide
Yogesh S. Sanghvi**, V. T. Ravikumar, Anthony N. Scozzari,
and Douglas L. Cole
Development Chemistry and Pharmaceutics, Isis Pharmaceuticals,
Inc., 2292 Faraday Avenue, Carlsbad, CA 92008, USA
Abstract: We have modified the current phosphoramidite-based,
solid-phase synthesis of 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 discussed are methodologies that allow reuse of valuable
materials such as amidites, 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.
* Lectures presented at the International Symposium
on Green Chemistry, Delhi, India, 10-13 January 2001. Other presentations
are published in this issue, pp. 77-203.
** Corresponding author.