摘要：

For the efficient synthesis of oligoribonucleotides by the 5′- O -(4,4′-dimethoxytrityl) phosphoramidite approach, the 2′- O -[1-(benzyloxy)ethyl]acetals 56 – 67 were investigated. Studies with the 2′- O -[1-(benzyloxy)ethyl]-5′- O -(dimethoxytrityl)ribonucleoside 3′-phosphoramidites 56 – 59 gave, however, only reasonable results. The oligoribonucleotides obtained showed some impurities since the acid stabilities of the acetal and dimethoxytrityl functions are too close to guarantee a high selectivity. A combination of new acid-labile protected 2′- O -protecting groups with the 2-(4-nitrophenyl)ethyl/[2-(4-nitrophenyl)ethoxy]carbonyl (npe/npeoc) strategy for base protection was more successful. The synthesis and physical properties of the monomeric building units and their intermediates 8 – 67 and the conditions for the automated generation of homo- and mixed oligoribonucleotides is described. The new 2′-acetal protecting group could be cleaved off in a two step procedure and was designed for levelling their stability with regard to the attached nucleobase as well. Therefore, we used the 1-{{3-fluoro-4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl (fnebe) moiety for the protection of 2′-OH of uridine, and for that of 2′-OH of A, C, and G, the 1-{{4-{{[2-(4-nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl (nebe) residue. After selective deprotection by β -elimination induced by a strong organic base like DBU, the remaining activated acetal was hydrolyzed under very mild acidic protic conditions, which reduced 2′-3′ isomerization and chain cleavage. Also storage, handling, and purification of the chemically and enzymatically sensitive oligomers was simplified by this approach.

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