Method for preparing oligonucleotides
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United States of America Patent
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app pub date -
Apr 3, 2009
filing date -
Jul 31, 2002
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Abandoned
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Abstract
A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large-scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3′-protected compound of formula:with a nucleotide derivative having a 5′-protection group, or reacting a 5′-protected compound of formulawith a nucleotide derivative having a 3′-protection group.
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