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filingDate 2002-06-28-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 2004-08-11-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber AR-036122-A1
titleOfInvention A COMPLEX OF SALT THAT INCLUDES AN N-ALQUILIMIDAZOL AND A 1,1-DIOXO-1,2-DIHIDRO-1L6-BENZO [D] -ISOTIAZOL-3-ONA AND A METHOD TO SYNTHEIZE OLIGONUCLEOTIDES USING PHOSPHORAMIDITE CHEMISTRY
abstract A salt complex comprising an N-alkylimidazole and a 1,1-dioxo-1,2-dihydro-1lambda6-benzo [d] isothiazol-3-one represented by structural formula (1) in which: p is 0 or an integer from 1 to 4; X7 is 0 or S; and R for each occurrence is a substituent. A method of synthesizing an oligonucleotide using phosphoramidite chemistry comprising coupling a nascent nucleoside or oligonucleotide having a free hydroxy or thiol group and a nucleoside phosphoramidite in the presence of a coupling agent, wherein the coupling agent is a 1, 1-dioxo-1,2-dihydro-1lambda6-benzo [d] isothiazol-3-one represented by the above formula (2) in which: p is 0 or an integer from 1 to 4; X7 is O or S; R for each occurrence is a substituent. A method for the synthesis of an oligonucleotide comprising coupling a nucleoside phosphoramidite, with a nascent nucleoside or oligonucleotide comprising a free hydroxy group, in the presence of an activator, wherein the activator comprises a mixture of 1,1-dioxo-1 , 2-dihydro-ilambda6-benzo [d] isothiazol-3-one- and an N-alkylimidazole. Synthetic oligonucleotides are important diagnostic tools for the detection of genetic and viral diseases. Additionally, oligonucleotides and modified oligonucleotides are of interest as therapeutic candidates that inhibit genetic expression or protein function. The large-scale synthesis of oligonucleotides for use as therapeutic candidates has become increasingly important since FDA approval of an oligonucleotide analog for the treatment of cytomegalovirus (CMV) and various other oligonucleotide analogs are currently in clinical trials. Amounts in kilograms of a purified oligonucleotide analog are needed for each clinical trial. Non-explosive activators are needed that promote the condensation of a nucleoside phosphoramidite with a nascent nucleoside or oligonucleotide and which can be used without increasing the secondary products so that oligonucleotides are more readily available for therapeutic and diagnostic use.
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