Convergent Solution Phase Synthesis of Chimeric Oligonucleotides by a 2+2 and 3+3 Phosphoramidite Strategy

Chih-Hau Chen; Wei-Yu Chen; Yu-Chie Chen; Ming-Juan Lee; Chyuan-Der Huang; Kaushik Chanda; Chung-Ming Sun

doi:10.1071/CH09298

RESEARCH ARTICLE

Convergent Solution Phase Synthesis of Chimeric Oligonucleotides by a 2+2 and 3+3 Phosphoramidite Strategy

Chih-Hau Chen ^A , Wei-Yu Chen ^A , Yu-Chie Chen ^A , Ming-Juan Lee ^B , Chyuan-Der Huang ^B , Kaushik Chanda ^A and Chung-Ming Sun ^A ^C

+ Author Affiliations

- Author Affiliations

^A Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300-10, Taiwan.

^B ScinoPharm Taiwan Ltd, Tainan 741-44, Taiwan.

^C Corresponding author. Email: cmsun@mail.nctu.edu.tw

Australian Journal of Chemistry 63(2) 227-235 https://doi.org/10.1071/CH09298
Submitted: 19 May 2009 Accepted: 27 October 2009 Published: 26 February 2010

Abstract

A chimeric oligonucleotide tetramer and hexamer were synthesized by the phosphoramidite approach using a 2+2 and 3+3 strategy, respectively. The concept of convergent synthesis provides an efficient route toward the synthesis of longer chimeric oligonucleotides, such as small interfering RNA oligonucleotides without the pollution of n – 1 or shorter failures. This methodology offers an efficient and economical way to scale-up the synthesis of high purity oligonucleotides for clinical trials and commercial uses.

Acknowledgements

The authors are thankful to National Science Council of Taiwan (NSC) and ScinoPharm^® Taiwan for financial assistance and National Center for High-Performance Computing for computer time and facilities.

References

Convergent Solution Phase Synthesis of Chimeric Oligonucleotides by a 2+2 and 3+3 Phosphoramidite Strategy

Abstract

Acknowledgements

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