title: Reverse-direction (5'-->3') synthesis of oligonucleotides containing a 3'-S-phosphorothiolate linkage and 3'-terminal 3'-thionucleosides.
abstract: The synthesis of oligodeoxynucleotides containing 3'-thionucleosides has been explored using a reverse-direction (5'-->3') approach, based on nucleoside monomers which contain a trityl- or dimethoxytrityl-protected 3'-thiol and a 5'-O-phosphoramidite. These monomers are relatively simple to prepare as trityl-based protecting groups were introduced selectively at a 3'-thiol in preference to a 5'-hydroxyl group. As an alternative approach, trityl group migration could be induced from the 5'-oxygen to the 3'-thiol function. 5'-->3' Synthesis of oligonucleotides gave relatively poor yields for the internal incorporation of 3'-thionucleosides [to give a 3'-S-phosphorothiolate (3'-SP) linkage] and multiple 3'-SP modifications could not be introduced by this method. However, the reverse direction approach provided an efficient route to oligonucleotides terminating with a 3'-thionucleoside. The direct synthesis of these thio-terminating oligomers has not previously been reported and the methods described are applicable to 2'-deoxy-3'-thionucleosides derived from thymine, cytosine and adenine.
authors.affiliation: Department of Chemistry, University of Liverpool, Crown Street, Liverpool, UK L69 7ZD.
authors.forename: James W
authors.initials: JW
authors.lastname: Gaynor
authors.forename: Michael M
authors.initials: MM
authors.lastname: Piperakis
authors.forename: Julie
authors.initials: J
authors.lastname: Fisher
authors.forename: Richard
authors.initials: R
authors.lastname: Cosstick
mesh_terms: D000577:Amides / Q000737:chemistry; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000235:genetics; D010756:Phosphoric Acids / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013872:Thionucleosides / Q000737:chemistry*
chemical_list: D000577:Amides; D009841:Oligonucleotides; D010756:Phosphoric Acids; D013438:Sulfhydryl Compounds; D013872:Thionucleosides; C011067:phosphoramidic acid