Synthesis and separation of diastereomers of deoxynucleoside 5'- 0(l-thio)triptaosphates

Jin Tann Chen, Stephen J. Benkovic

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Abstract

Treatment of unprotected nucleosides with an excess of phosphorous acid and stoichiometric proportions of N,N'-di-p-tolylcarbodiimide in anhydrous pyridine gives predominantly deoxynucleoside monophosphites and minor amounts of 5-3'-dlphosphites; for deoxyadenosine and deoxyguanosine, the monophos-phite products are exclusively 5'-phosphites, whereas for deoxycytidine and thymidine, the yields of the 5'-phosphites are 85% and 92% respectively. Sulfuriiation of these deoxynucleoside monophosphites with sulfur in the presence of trlalkylamines and trimethylsilyl chloride in dry pyridine nearly quantitatively produces deoxynudeoside phosphorothioates. Condensation of these phosphorothioates with pyrophoaphate forms diastereomers of the α-thio-derivatives of deoxynucleoside triphosphate. The individual diaatereomers of each deoxynucleoside 5'-O-(l-thio)triphosphate can be separated, on a preparative scale, by ion exchange chromatography.

Original languageEnglish (US)
Pages (from-to)3737-3751
Number of pages15
JournalNucleic acids research
Volume11
Issue number11
DOIs
StatePublished - Jun 11 1983

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All Science Journal Classification (ASJC) codes

  • Genetics

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