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

Jin Tann Chen, Stephen J. Benkovic

Research output: Contribution to journalArticle

25 Citations (Scopus)

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

Fingerprint

Phosphites
Deoxycytidine
Deoxyguanosine
Ion Exchange Chromatography
Nucleosides
Sulfur
Thymidine
triphosphoric acid
pyridine
trimethylsilyl chloride
2'-deoxyadenosine
phosphonic acid

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Chen, Jin Tann ; Benkovic, Stephen J. / Synthesis and separation of diastereomers of deoxynucleoside 5'- 0(l-thio)triptaosphates. In: Nucleic acids research. 1983 ; Vol. 11, No. 11. pp. 3737-3751.
@article{b2e408530a9641a6abd6ee4fa636741e,
title = "Synthesis and separation of diastereomers of deoxynucleoside 5'- 0(l-thio)triptaosphates",
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.",
author = "Chen, {Jin Tann} and Benkovic, {Stephen J.}",
year = "1983",
month = "6",
day = "11",
doi = "10.1093/nar/11.11.3737",
language = "English (US)",
volume = "11",
pages = "3737--3751",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "11",

}

Synthesis and separation of diastereomers of deoxynucleoside 5'- 0(l-thio)triptaosphates. / Chen, Jin Tann; Benkovic, Stephen J.

In: Nucleic acids research, Vol. 11, No. 11, 11.06.1983, p. 3737-3751.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis and separation of diastereomers of deoxynucleoside 5'- 0(l-thio)triptaosphates

AU - Chen, Jin Tann

AU - Benkovic, Stephen J.

PY - 1983/6/11

Y1 - 1983/6/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0021100902&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021100902&partnerID=8YFLogxK

U2 - 10.1093/nar/11.11.3737

DO - 10.1093/nar/11.11.3737

M3 - Article

C2 - 6856463

AN - SCOPUS:0021100902

VL - 11

SP - 3737

EP - 3751

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 11

ER -