Synthesis of 2′-modified oligodeoxynucleotides via on-column conjugation

J. T. Hwang, M. M. Greenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Oligodeoxynucleotides modified at the 2′-position of 2′-amino-2′-deoxyuridine or uridine were prepared in high yield and purity using phosphoramidites 2 and 3, respectively. Oligodeoxynucleotide conjugates were prepared on the solid-phase synthesis support following selective unmasking of the nucleophile incorporated in these phosphoramidites. Synthesis of oligodeoxynucleotides modified at the 2′-position of an internal nucleotide provides molecules that are complementary to those previously prepared via a similar approach using C5-substituted pyrimidines. The efficiency of functionalization of the 2′-O-alkylamino-uridine derived from 3 in a protected oligodeoxynucleotide was less susceptible to steric hindrance than the 2′-amino-2′-deoxyuridine in the same polymeric substrate. However, the greater reactivity of the 2′-O-alkylamine containing nucleotide gave rise to undesired acetamide formation resulting from nucleophilic attack on the 5′-terminal acetate in capped failure sequences. This problem was overcome by using 2,2,2-trimethylacetyl anhydride as a capping agent during the automated synthesis cycles. Finally, the efficiency of the photochemical unmasking of the support bound alkylamine on a 1 μmole scale was improved by using two 20 min photolysis cycles, coupled with removing reaction byproducts between cycles.

Original languageEnglish (US)
Pages (from-to)363-369
Number of pages7
JournalJournal of Organic Chemistry
Volume66
Issue number2
DOIs
StatePublished - Jan 26 2001
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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