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Pure Appl. Chem. Vol. 73, No. 1, pp. 175-180 (2001)

Pure and Applied Chemistry

Vol. 73, Issue 1

Applications of green chemistry in the manufacture of oligonucleotide drugs*

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.

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