Subscribe to RSS
DOI: 10.1055/s-0041-1738455
Solvent Selection in the Detritylation Reaction for the Solid-Phase Synthesis of Oligonucleotides
The 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.
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 - solventSupporting 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
© 2023. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References and Notes
- 1 Matteucci MD, Caruthers MH. J. Am. Chem. Soc. 1981; 103: 3185
- 2 Beaucage SL, Caruthers MH. Tetrahedron Lett. 1981; 22: 859
- 3 Schaller H, Weimann G, Lerch B, Khorana HG. J. Am. Chem. Soc. 1963; 85: 3821
- 4 Tram K, Sanghvi YS, Yan H. Nucleosides, Nucleotides Nucleic Acids 2011; 30: 12
- 5 Moore MN, Andrade MA, Scozzari AN, Krotz AH. Org. Process Res. Dev. 2004; 8: 271
- 6 Kim SW, Cho YI, Jung KE. Bull. Korean Chem. Soc. 2021; 42: 1296
- 7 Andrews BI, Antia FD, Brueggemeier SB, Diorazio LJ, Koenig SG, Kopach ME, Lee H, Olbrich M, Watson AL. J. Org. Chem. 2021; 86: 49
- 8 Maria P.-C, Gal J.-F. J. Phys. Chem. 1985; 89: 1296
- 9 Dreyfuss MP, Westfahl JC, Dreyfuss P. Macromolecules 1968; 1: 437
- 10 Smirnov YN, Volkov VP, Oleinik EF, Komarov BA, Rozenberg BA, Yenikolopyan NS. Polymer Sci. U.S.S.R. 1974; 16: 846
- 11 Paul CH, Royappa AT. Nucleic Acids Res. 1996; 24: 3048
- 12 Appelman EH, Dunkelberg O, Kol M. J. Fluorine Chem. 1992; 56: 199
- 13 Salnikov GE, Genaev AM, Vasiliev VG, Shubin VG. Org. Biomol. Chem. 2012; 10: 2282
- 14 Rozenberg M, Loewenschuss A, Nielsen CJ. J. Mol. Struct. 2020; 1199: 126948
- 15 Makovky A, Lenji L. Chem. Rev. 1958; 58: 627
- 16 Zhou X, Kiesman WF, Yan W, Jiang H, Antia FD, Yang J, Fillon YA, Xiao L, Shi X. J. Org. Chem. 2022; 87: 2087