Improved synthesis of adenosine cyclic 3′,5′idates via anhydrides. preparation of adenosine cylic 3′,5′-(rp)-and (sp)-n-methylphosphorami date

S. Bottka, J. Tomasz

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4 Citations (Scopus)

Abstract

The two-step method for the preparation of adenosine cyclic 3′,3′-phosphoramidate diastereoisomers, which involves the activation of adenosine cyclic 3′,5′-monophos-phate (1) with an acid chloride and in situ aminolysis of the anhydride intermediate (Bentrude, W.G.; Tomasz, J. Synthesis 1984, 27; Bottka, S.; Tomasz, J. Tetrahedron Lett.1985, 24, 2909), has been improved. The best yields were attained when 1_ was reacted with 4.4 molar equivalents of phosphorus oxychloride in trimethyl phosphate at 0°C for 3 h, and the solution of phosphorus oxychloride in trimethyl phosphate was pretreated with 0.5 molar equivalent of water at room temperature for 20 min. Rp and Sp diastereoisomers of adenosine cyclic 3′,3′-N-methylphosphoramidate and N,N-dimethylphos-phoramidate have been synthesized under these experimental conditions.

Original languageEnglish
Pages (from-to)307-319
Number of pages13
JournalNucleosides and Nucleotides
Volume7
Issue number3
DOIs
Publication statusPublished - Jun 1 1988

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Anhydrides
Adenosine
Chlorides
Chemical activation
Temperature
Acids
Water
phosphoryl chloride
trimethyl phosphate

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

Cite this

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abstract = "The two-step method for the preparation of adenosine cyclic 3′,3′-phosphoramidate diastereoisomers, which involves the activation of adenosine cyclic 3′,5′-monophos-phate (1) with an acid chloride and in situ aminolysis of the anhydride intermediate (Bentrude, W.G.; Tomasz, J. Synthesis 1984, 27; Bottka, S.; Tomasz, J. Tetrahedron Lett.1985, 24, 2909), has been improved. The best yields were attained when 1_ was reacted with 4.4 molar equivalents of phosphorus oxychloride in trimethyl phosphate at 0°C for 3 h, and the solution of phosphorus oxychloride in trimethyl phosphate was pretreated with 0.5 molar equivalent of water at room temperature for 20 min. Rp and Sp diastereoisomers of adenosine cyclic 3′,3′-N-methylphosphoramidate and N,N-dimethylphos-phoramidate have been synthesized under these experimental conditions.",
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N2 - The two-step method for the preparation of adenosine cyclic 3′,3′-phosphoramidate diastereoisomers, which involves the activation of adenosine cyclic 3′,5′-monophos-phate (1) with an acid chloride and in situ aminolysis of the anhydride intermediate (Bentrude, W.G.; Tomasz, J. Synthesis 1984, 27; Bottka, S.; Tomasz, J. Tetrahedron Lett.1985, 24, 2909), has been improved. The best yields were attained when 1_ was reacted with 4.4 molar equivalents of phosphorus oxychloride in trimethyl phosphate at 0°C for 3 h, and the solution of phosphorus oxychloride in trimethyl phosphate was pretreated with 0.5 molar equivalent of water at room temperature for 20 min. Rp and Sp diastereoisomers of adenosine cyclic 3′,3′-N-methylphosphoramidate and N,N-dimethylphos-phoramidate have been synthesized under these experimental conditions.

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