Automated Solid-Phase Synthesis of RNA Oligonucleotides Containing a Nonbridging Phosphorodithioate Linkage via Phosphorothioamidites

• Published in: Journal of organic chemistry Vol. 77; no. 21; pp. 9889 - 9892
• Main Authors: Li, Nan-Sheng, Frederiksen, John K, Piccirilli, Joseph A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 02.11.2012; Amer Chemical Soc
• Subjects: Analytical, structural and metabolic biochemistry; Base Sequence; Biological and medical sciences; Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Organic; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Molecular Structure; Nucleic acids; Nucleosides, nucleotides and oligonucleotides; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Organic chemistry; Organometalloidal and organometallic compounds; Organophosphorus Compounds - chemistry; Organothiophosphorus Compounds - chemistry; P derivatives; Phosphates - chemistry; Physical Sciences; Preparations and properties; Ribonucleosides - chemistry; RNA - chemical synthesis; RNA - chemistry; Rna, ribonucleoproteins; Science & Technology; Solid-Phase Synthesis Techniques; TRIESTER METHOD; THIOAMIDITES; SITE; OLIGODEOXYNUCLEOTIDES; DNA; SUBSTITUTIONS; STEREOCHEMISTRY; OLIGODEOXYRIBONUCLEOSIDE PHOSPHORODITHIOATES; TETRAHYMENA RIBOZYME REACTION; DINUCLEOSIDE PHOSPHORODITHIOATES; One pot reaction; RNA; Thioamide; Nucleotide; Nucleoside; Oligoribonucleotide; Oligonucleotide; Solid phase; Ribonucleoside; Chemical synthesis; Organic dithiophosphate; Phosphorus Organic compounds
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo301834p

This work describes a general method for the synthesis of oligoribonucleotides containing a site-specific nonbridging phosphorodithioate linkage via automated solid-phase synthesis using 5′-O-DMTr-2′-O-TBS-ribonucleoside 3′-N,N-dimethyl-S-(2,4-dichlorobenzyl) phosphorothioamidites (2a–2d). The 3′-phosphorothioamidites (2a–2d) can be conveniently prepared in good yields (86–99%) via a one-pot reaction from the corresponding 5′-O-DMTr-2′-O-TBS-ribonucleosides (1a–1d).