title: Synthesis of phosphorothioamidites derived from 3'-thio-3'-deoxythymidine and 3'-thio-2',3'-dideoxycytidine and the automated synthesis of oligodeoxynucleotides containing a 3'-S-phosphorothiolate linkage.
abstract: The synthesis of N4-benzoyl-5'-O-dimethoxytrityl-2',3'-dideoxy-3'-thiocytidine and its phosphorothioamidite is described for the first time, together with a shortened procedure for the preparation of 5'-O-dimethoxytrityl-3'-deoxy-3'-thiothymidine and its corresponding phosphorothioamidite. The first fully automated coupling procedure for the incorporation of a phosphorothioamidite into a synthetic oligodeoxynucleotide has been developed, which conveniently uses routine activators and reagents. Coupling yields using this protocol were in the range of 85-90% and good yields of singularly modified oligonucleotides were obtained. Coupling yields were also equally good when performed on either a 0.2 or 1 micro mol reaction column, thus facilitating large scale syntheses required for mechanistic studies.
authors.affiliation: Department of Chemistry, University of Liverpool, Crown Street, Liverpool L69 7ZD, UK.
authors.forename: Ghalia
authors.initials: G
authors.lastname: Sabbagh
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Fettes
authors.forename: Rajendra
authors.initials: R
authors.lastname: Gosain
authors.forename: Ian A
authors.initials: IA
authors.lastname: O'Neil
authors.forename: Richard
authors.initials: R
authors.lastname: Cosstick
mesh_terms: D001331:Automation / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000737:chemistry*; D054306:Dideoxynucleotides; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D010710:Phosphates / Q000737:chemistry*; D013872:Thionucleosides / Q000138:chemical synthesis / Q000737:chemistry; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: C483771:3'-S-(2-Cyanoethyl-N,N-diisopropylphosphorothioamidite)- 3'-deoxy-5'-O-(4,4'-dimethoxytrityl)thymidine; C483772:3'-S-(2-Cyanoethyl-N,N-diisopropylphosphorothioamidite)- N4-benzoyl-3'-deoxy-5'-O-(4,4'-dimethoxytrityl)cytidine; C465503:3'-S-phosphorothiolate; C483774:3'-thio-2',3'-dideoxycytidine; C483773:3'-thio-3'-deoxythymidine; D015224:Dideoxynucleosides; D054306:Dideoxynucleotides; D009838:Oligodeoxyribonucleotides; D009946:Organothiophosphorus Compounds; D010710:Phosphates; D013872:Thionucleosides; D016047:Zalcitabine; D013936:Thymidine