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Synlett 2024; 35(06): 672-676
DOI: 10.1055/s-0041-1738455
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Special Issue to Celebrate the Centenary Year of Prof. Har Gobind Khorana

Solvent Selection in the Detritylation Reaction for the Solid-Phase Synthesis of Oligonucleotides

Quanjian Li
a   Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON L2S 3A1, Canada
,
Yogesh S. Sanghvi∗
b   Rasayan Inc., 2802 Crystal Ridge Road, Encinitas, CA 92024-6615, USA
,
Hongbin Yan∗
a   Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON L2S 3A1, Canada
› Author AffiliationsThe work was supported by the Natural Sciences and Engineering Research Council of Canada, the Brock-Niagara Validation, Prototyping and Manufacturing Institute (VPMI) and the Government of Canada through Federal Economic Development Agency for Southern Ontario (FedDev Ontario), and Rasayan Inc.
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Abstract

This study examined the choice of solvent in the detritylation reaction for solid-phase oligonucleotide synthesis. In addition to being chemically inert under detritylation conditions, such a solvent should not bind with acid used in this reaction. These considerations explained the only two choices of solvent currently used in the detritylation reaction: dichloromethane and toluene. Other solvents, such as ethyl acetate, acetonitrile, THF, and nitromethane are shown by NMR spectroscopy to bind with trichloroacetic acid. Therefore, these are undesirable solvents for the detritylation reaction, confirmed by solid-phase synthesis experiments.

Key words

solid-phase synthesis - oligonucleotides - detritylation - trityl cation - solvent - acid binding - solvent

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0041-1738455.
  • Supporting Information


Publication History

Received: 16 June 2023

Accepted after revision: 02 August 2023

Article published online:
11 October 2023

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