Synthesis and Properties of Phosphoramidite Derivatives of MOdified Nucleosides

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Protected N⁶-methyl-2'-deoxyadenosine (d-m⁶A), 2-amino-2'-deoxyadenosine (d-a²A), 2'-deoxyinosine (dI), 5-methyl-2'-deoxycytidine (d-m⁵C) and deoxyuridine (dU) were reacted with bis(diisopropylamino)methoxyphosphine in the presence of diisopropylammonium tetrazolide as the activating reagent to gie the corresponding phosphoramidite derivatives in yields of 100, 65, 90, 78 and 65%, respectively. The ³¹P-nuclear magnetic resonance spectra of the products were measured. Using these compounds, dinucleotides and trinucleotides were synthesized on a long-chain alkylamine controlled pore glass (LCA-CPG) in quantitative yields.The stability of 6-methyldeoxyadenosine and N, N-diisobutyryl-2-aminodeoxyadenosine to acid was examined. When protected di- and trinucleotides (m⁶A-T, a²A-T, T-m⁶A-T, T-a²A-T)bound to the support (LCA-CPG) were treated with 3% trichloroacetic acid in dichloromethane, depurination was negligible within 10 min (dinucleotide) or 60 min (trinucleotide).