RESUMEN
New 3'-terminal deoxyribonucleoside-loading reagents having a silyl-type linker were developed. They were effectively introduced into polymer supports under the conditions of Huisgen [3 + 2] cycloaddition without base protection. Moreover, four unmodified DNA oligomers d[TACCTAAATCCAX] (X = T, A, C, and A) and a base-labile modified DNA 12mer d[A*C*T*C*C*GT*C*T*A*C*G] 16 (A* = 6-N-acetyl-8-aza-7-deaza-2'-deoxyadenosine, C* = 4-N-acetyl-2'-deoxyctydine, T* = 2-thio-T) were successfully synthesized by cleavage of the silyl-type linker using Bu(4)NF under neutral conditions in our N-unprotected phosphoramidite method. In this paper, we also report a new reaction of chlorination of cytosine base using 1,3-dichloro-5,5-dimethylhydantoin.
Asunto(s)
Nucleósidos/química , Polímeros/química , Catálisis , Compuestos de Cloro/química , Cromatografía Líquida de Alta Presión , Cobre/química , ADN/química , Estructura MolecularRESUMEN
In this study, we developed new 3'-terminal deoxyribonucleoside-loading reagents 1 with a new silyl-type linker. These reagents could increase the efficiency of introduction of 3'-terminal deoxyribonucleoside components into polymer supports to a level of 17-29micromol/g. The efficiency was higher than that of previous T-loading reagents because reagents 1 contain a 4-aminobutyryl residue as a spacer. Moreover, we could synthesize not only unmodified DNA oligomers but also a base-labile modified DNA oligomer using resins 9a-d in the activated phosphite method without base protection.
Asunto(s)
Oligodesoxirribonucleótidos/síntesis química , Silanos/química , Estructura Molecular , Oligodesoxirribonucleótidos/química , Silanos/síntesis química , EstereoisomerismoRESUMEN
New silyl-type linkers 2 and 3 were developed for the synthesis of oligonucleotides having base-labile functional groups in the phosphoramidite method without base protection. These linkers could be introduced into polymer supports in high yields and easily cleaved under neutral conditions. Particularly, the use of the N-unprotected phosphoramidite building block 3 having a silyl-type linker enabled us to synthesize oligodeoxynucleotides without protecting groups for the amino groups of 3'-terminal deoxyribonucleosides.