Chemical synthesis of RNA with base-labile 2'-o-(pivaloyloxymethyl)-protected ribonucleoside phosphoramidites

Abstract

The efficiency of chemical RNA synthesis has been radically improved by the use of pivaloyloxymethyl (PivOM) groups as 2'-protection, containing an acetal spacer that minimizes the steric effect of the ester group on the neighboring amidite during the coupling. However, the major benefit of the base-labile PivOM groups is their simple removal upon standard basic conditions applied to deprotect the RNA and release it from solid supports. Combined with standard acyl groups for nucleobases, cyanoethyl groups for phosphates, and base-cleavable linkers, PivOM groups make RNA deprotection as simple as DNA deprotection. Thus, no additional deprotection step with tedious desalting workup procedures is required, and RNA synthesis becomes as convenient and efficient as DNA synthesis.