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Solid-Phase Synthesis and Hybrization Behavior of Partially 2′/3′-O-Acetylated RNA Oligonucleotides

“…Merk et al have pioneered the use of (2-cyanoethyloxy)carbonyl (ceoc) protecting groups to protect the exocyclic amino groups of adenosine, cytidine and guanosine (A, C, and G). 22 The non-nucleophilic strong base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was used to remove ceoc groups under nonprotic reaction conditions via a β-elimination process that was thought to be compatible with the maintenance of 2′/3′- O -acetylation. 23 Moreover, another advantage of this strategy is that the deprotection of cyanoethyl-protected phosphate groups can be accomplished in the same step.…”

“… 25 The protection of the exocyclic amino groups of A and C was effected according to Pfleiderer’s strategy. 22 …”

“…Finally, the introduction of the N 2 -ceoc protecting group was effected with 2-cyanoethyl carbonochloridate 1 to afford the nucleobase-protected guanosine 5 in 96% yield. 22 …”

“…25 The protection of the exocyclic amino groups of A and C was effected according to Pfleiderer's strategy. 22 Nucleobase protection of G required several steps to install both the O 6 -npe and the N 2 -ceoc protecting groups (Scheme 2). Preliminary experiments revealed that per-acylation of guanosine was difficult because, while the hydroxyl groups underwent smooth reaction, the acetylation of the N 2 -position was very sluggish and did not proceed to completion.…”

“…Finally, the introduction of the N 2 -ceoc protecting group was effected with 2-cyanoethyl carbonochloridate 1 to afford the nucleobase-protected guanosine 5 in 96% yield. 22 Synthesis of the 2′/3′-O-Acetyl RNA Phosphoramidites. With the nucleobase-protected materials in hand, we envisaged two alternative ways to synthesize the 2′/3′-O-acetyl RNA phosphoramidite monomers depending on the order of the tritylation and acetylation steps.…”