LARGE-SCALE SYNTHESIS OF “Cpep” RNA MONOMERS AND THEIR APPLICATION IN AUTOMATED RNA SYNTHESIS

Abstract

Small interfering RNAs (siRNA) are the latest candidates for oligonucleotide-based therapeutics. Should siRNA be successful in clinical trials, a huge demand for synthetic RNA is anticipated. We believe that 1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl (Cpep) is an ideal 2′-protecting group for large-scale syntheses. Unlike 2′-silyl groups, mild acid hydrolysis instead of fluoride ion is used for the 2′-deprotection. The syntheses of 2′-Cpep protected nucleosides (A, C, G, and U) has been accomplished on a 0.5 Kg scale. The 2′-Cpep monomers were transformed into 3′-O-phosphoramidites for conventional automated solid-phase synthesis. Cost-effective processes for large-scale synthesis of Cpep monomers and initial automated solid-phase synthesis are demonstrated.

Keywords:

• 2′-Protecting Groups
• Phosphoramidites
• Oligoribonucleotides