Synthesis and structural study of variously oxidized diastereomeric 5′-dimethoxytrityl-thymidine- 3′-O-[O-(2-cyanoethyl)-N, N-diisopropyl] phosphoramidite derivatives. Comparison of the effects of the P = O,P = S, and P = Se functions on the NMR spectral and chromatographic properties

Eszter Gács-Baitz, Ferenc Sipos, Orsolya Egyed, Gyula Sági

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Abstract

RP- and SP- diastereomers of 5′-dimethoxytrityl-thymidine- 3′-O-[O-(2-cyanoethyl)-N, N-diisopropyl]-phosphoramidite (T-CED) were separated by silica gel chromatography. Oxidation of both isomers with H2O2, elemental sulfur and selenium, respectively, resulted in the corresponding oxidized analogues in nearly quantitative yields. All reactions were found to proceed with retention of P-configuration. This was confirmed by thorough NMR analysis which, in addition, aimed to study the spectral properties of the diastereomers with special respect to differences in the heteroatom effect of the O, S and Se atoms, double-bonded to the phosphorus, on the vicinal carbon-phosphorus couplings. It was found that the changes in the ΔJ (=3J(P,C4′) - 3J(P,C2′)) values were basically induced by the electronegativity of the heteroatoms, rather than differences in the rotational preferences about the C3′-O3′ bond. The impact of the benzene solvent on the above couplings is also discussed. The effect of these heteroatoms on the chromatographic (normal and reverse phase HPLC) behavior of the compounds was also investigated and the reverse phase HPLC profiles showed an unambiguous correlation between the electronegativity of the heteroatoms and the chromatographic mobility of the analogues.

Original languageEnglish
Pages (from-to)663-673
Number of pages11
JournalChirality
Volume21
Issue number7
DOIs
Publication statusPublished - Oct 5 2009

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Keywords

  • HPLC analyses
  • NMR studies
  • P-chiral phosphates
  • Stereochemistry of oxidations
  • Vicinal carbon-phosphorus coupling

ASJC Scopus subject areas

  • Analytical Chemistry
  • Catalysis
  • Pharmacology
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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