Preparation of Zwitterionic Ribonucleoside Phosphoramidites for Solid-Phase siRNA Synthesis

• Published in: Journal of organic chemistry Vol. 73; no. 13; pp. 4994 - 5002
• Main Authors: Smicius, Romualdas, Engels, Joachim W
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.07.2008; Amer Chemical Soc
• Subjects: Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Organic; Exact sciences and technology; Nucleic Acid Conformation; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Organophosphorus Compounds - chemical synthesis; Physical Sciences; Preparations and properties; Ribonucleosides - chemistry; RNA, Small Interfering - chemical synthesis; Science & Technology; RNA INTERFERENCE; THERAPEUTICS; TECHNOLOGIES; DUAL RECOGNITION; ACIDS; ANTISENSE; 2'-AMINOETHOXY-MODIFIED OLIGONUCLEOTIDES; EXONUCLEASE RESISTANCE; DOUBLE-STRANDED DNA; RNA; Organic phosphoramidite; Zwitterion; siRNA; Oligomer; Antisense oligonucleotide; Alkylation; Phosphorus Organic compounds; Amine; Nucleotide; Organic phosphate; Nucleoside; Solid phase; Ribonucleoside; Chemical synthesis
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo800451m

RNA oligomers, carrying 2′-O-modified nucleosides, proved to be extremely useful in different antisense strategies, including RNAi. The 2′-O-alkyl modification, carrying an amino functionality, deserves special attention due to its ability to neutralize the negatively charged phosphate backbone, leading to improved physicochemical and pharmaceutical properties of antisense agents. Here, we report a very short, convenient, and straightforward synthesis of phosphoramidites for all four 2′-aminoethyl-modified natural ribonucleosides, where the aminoethyl group is introduced in a single alkylation step.