title: 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.
authors.affiliation: Department of Biochemical and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: R T
authors.initials: RT
authors.lastname: Pon
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.forename: T
authors.initials: T
authors.lastname: Prabhavalkar
authors.forename: T
authors.initials: T
authors.lastname: Mishra
authors.forename: B
authors.initials: B
authors.lastname: Kulkarni
authors.forename: Y S
authors.initials: YS
authors.lastname: Sanghvi
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D019075:Electrophoresis, Capillary; D005459:Fluorides / Q000737:chemistry; D006868:Hydrolysis; D046911:Macromolecular Substances / Q000737:chemistry; D008956:Models, Chemical; D008967:Molecular Biology / Q000379:methods*; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry; D012313:RNA / Q000138:chemical synthesis* / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry*; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D005459:Fluorides; D046911:Macromolecular Substances; D009705:Nucleosides; D009841:Oligonucleotides; D012313:RNA; D034741:RNA, Small Interfering; D000099166:Polyacrylamides