Method for chemical synthesis of oligonucleotides

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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5483351, C07H 2100

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060404396

ABSTRACT:
The present invention provides a practical method capable of chemically synthesizing a 100-mer or more long-chain oligonucleotide easily and reliably and a novel compound used in said method. The present invention relates to a method for chemical synthesis of an oligonucleotide by the phosphoroamidite method, which comprises preparing a base moiety-unprotected nucleoside phosphoroamidite from a base moiety-unprotected nucleoside by use of an imidazole trifluoromethanesulfonate represented by the following chemical formula, and coupling said base moiety-unprotected nucleotide phosphoroamidite in a predetermined order to chemically synthesize an oligonucleotide consisting of a specific nucleotide sequence, as well as to an imidazole trifluoromethanesulfonate represented by the chemical formula. ##STR1##

REFERENCES:
patent: 5077285 (1991-12-01), Claremon et al.
Arnold et al., "Chloridite and Amidite Automated Synthesis of Oligodeoxyribonucleotides Using Amidine Protected Nucleosides," reported in "7th Symposium Chem. Nucleic Acid Components," Nucleic Acids Symposium Series, 18, 181-184 (Aug. 30, 1987); Chemical Abstracts, 108(19), p. 692, Abstr. No. 167875z (May 9, 1988).
Hayakawa et al., "Benzimidazolium Triflate as an Efficient Promoter for Nucleotide Synthesis via the Phosphoramidite Method," J. Organic Chemistry, 61(23), 7996-7997 (Nov. 15, 1996).
Pirrung et al., "Proofing of Photolithographic DNA Synthesis with 3',5'-Dimethoxybenzoinyloxycarbonyl-Protected Deoxynucleoside Phosphoramidites," J. Organic Chemistry, 63(2), 241-246 (Jan. 23, 1998).
Effenberger et al., Trifluoromethanesulfonic Imidazolide--A Convenient Reagent for Introducing the Triflate Group, Tetrahedron Letters, 1980(45), 3947-3948 (Sep. 1980).

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